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• Volume 76, Issue 2
• COVID-19 pandemic and its impact on social relationships and health
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• http://orcid.org/0000-0003-1512-4471 Emily Long 1 ,
• Susan Patterson 1 ,
• Karen Maxwell 1 ,
• Carolyn Blake 1 ,
• http://orcid.org/0000-0001-7342-4566 Raquel Bosó Pérez 1 ,
• Ruth Lewis 1 ,
• Mark McCann 1 ,
• Julie Riddell 1 ,
• Kathryn Skivington 1 ,
• Rachel Wilson-Lowe 1 ,
• http://orcid.org/0000-0002-4409-6601 Kirstin R Mitchell 2
• 1 MRC/CSO Social and Public Health Sciences Unit , University of Glasgow , Glasgow , UK
• 2 MRC/CSO Social and Public Health Sciences Unit, Institute of Health & Wellbeing , University of Glasgow , Glasgow , UK
• Correspondence to Dr Emily Long, MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Glasgow G3 7HR, UK; emily.long{at}glasgow.ac.uk

This essay examines key aspects of social relationships that were disrupted by the COVID-19 pandemic. It focuses explicitly on relational mechanisms of health and brings together theory and emerging evidence on the effects of the COVID-19 pandemic to make recommendations for future public health policy and recovery. We first provide an overview of the pandemic in the UK context, outlining the nature of the public health response. We then introduce four distinct domains of social relationships: social networks, social support, social interaction and intimacy, highlighting the mechanisms through which the pandemic and associated public health response drastically altered social interactions in each domain. Throughout the essay, the lens of health inequalities, and perspective of relationships as interconnecting elements in a broader system, is used to explore the varying impact of these disruptions. The essay concludes by providing recommendations for longer term recovery ensuring that the social relational cost of COVID-19 is adequately considered in efforts to rebuild.

• inequalities

Data availability statement

Data sharing not applicable as no data sets generated and/or analysed for this study. Data sharing not applicable as no data sets generated or analysed for this essay.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/ .

https://doi.org/10.1136/jech-2021-216690

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Introduction

Infectious disease pandemics, including SARS and COVID-19, demand intrapersonal behaviour change and present highly complex challenges for public health. 1 A pandemic of an airborne infection, spread easily through social contact, assails human relationships by drastically altering the ways through which humans interact. In this essay, we draw on theories of social relationships to examine specific ways in which relational mechanisms key to health and well-being were disrupted by the COVID-19 pandemic. Relational mechanisms refer to the processes between people that lead to change in health outcomes.

At the time of writing, the future surrounding COVID-19 was uncertain. Vaccine programmes were being rolled out in countries that could afford them, but new and more contagious variants of the virus were also being discovered. The recovery journey looked long, with continued disruption to social relationships. The social cost of COVID-19 was only just beginning to emerge, but the mental health impact was already considerable, 2 3 and the inequality of the health burden stark. 4 Knowledge of the epidemiology of COVID-19 accrued rapidly, but evidence of the most effective policy responses remained uncertain.

The initial response to COVID-19 in the UK was reactive and aimed at reducing mortality, with little time to consider the social implications, including for interpersonal and community relationships. The terminology of ‘social distancing’ quickly became entrenched both in public and policy discourse. This equation of physical distance with social distance was regrettable, since only physical proximity causes viral transmission, whereas many forms of social proximity (eg, conversations while walking outdoors) are minimal risk, and are crucial to maintaining relationships supportive of health and well-being.

The aim of this essay is to explore four key relational mechanisms that were impacted by the pandemic and associated restrictions: social networks, social support, social interaction and intimacy. We use relational theories and emerging research on the effects of the COVID-19 pandemic response to make three key recommendations: one regarding public health responses; and two regarding social recovery. Our understanding of these mechanisms stems from a ‘systems’ perspective which casts social relationships as interdependent elements within a connected whole. 5

Social networks

Social networks characterise the individuals and social connections that compose a system (such as a workplace, community or society). Social relationships range from spouses and partners, to coworkers, friends and acquaintances. They vary across many dimensions, including, for example, frequency of contact and emotional closeness. Social networks can be understood both in terms of the individuals and relationships that compose the network, as well as the overall network structure (eg, how many of your friends know each other).

Social networks show a tendency towards homophily, or a phenomenon of associating with individuals who are similar to self. 6 This is particularly true for ‘core’ network ties (eg, close friends), while more distant, sometimes called ‘weak’ ties tend to show more diversity. During the height of COVID-19 restrictions, face-to-face interactions were often reduced to core network members, such as partners, family members or, potentially, live-in roommates; some ‘weak’ ties were lost, and interactions became more limited to those closest. Given that peripheral, weaker social ties provide a diversity of resources, opinions and support, 7 COVID-19 likely resulted in networks that were smaller and more homogenous.

Such changes were not inevitable nor necessarily enduring, since social networks are also adaptive and responsive to change, in that a disruption to usual ways of interacting can be replaced by new ways of engaging (eg, Zoom). Yet, important inequalities exist, wherein networks and individual relationships within networks are not equally able to adapt to such changes. For example, individuals with a large number of newly established relationships (eg, university students) may have struggled to transfer these relationships online, resulting in lost contacts and a heightened risk of social isolation. This is consistent with research suggesting that young adults were the most likely to report a worsening of relationships during COVID-19, whereas older adults were the least likely to report a change. 8

Lastly, social connections give rise to emergent properties of social systems, 9 where a community-level phenomenon develops that cannot be attributed to any one member or portion of the network. For example, local area-based networks emerged due to geographic restrictions (eg, stay-at-home orders), resulting in increases in neighbourly support and local volunteering. 10 In fact, research suggests that relationships with neighbours displayed the largest net gain in ratings of relationship quality compared with a range of relationship types (eg, partner, colleague, friend). 8 Much of this was built from spontaneous individual interactions within local communities, which together contributed to the ‘community spirit’ that many experienced. 11 COVID-19 restrictions thus impacted the personal social networks and the structure of the larger networks within the society.

Social support

Social support, referring to the psychological and material resources provided through social interaction, is a critical mechanism through which social relationships benefit health. In fact, social support has been shown to be one of the most important resilience factors in the aftermath of stressful events. 12 In the context of COVID-19, the usual ways in which individuals interact and obtain social support have been severely disrupted.

One such disruption has been to opportunities for spontaneous social interactions. For example, conversations with colleagues in a break room offer an opportunity for socialising beyond one’s core social network, and these peripheral conversations can provide a form of social support. 13 14 A chance conversation may lead to advice helpful to coping with situations or seeking formal help. Thus, the absence of these spontaneous interactions may mean the reduction of indirect support-seeking opportunities. While direct support-seeking behaviour is more effective at eliciting support, it also requires significantly more effort and may be perceived as forceful and burdensome. 15 The shift to homeworking and closure of community venues reduced the number of opportunities for these spontaneous interactions to occur, and has, second, focused them locally. Consequently, individuals whose core networks are located elsewhere, or who live in communities where spontaneous interaction is less likely, have less opportunity to benefit from spontaneous in-person supportive interactions.

However, alongside this disruption, new opportunities to interact and obtain social support have arisen. The surge in community social support during the initial lockdown mirrored that often seen in response to adverse events (eg, natural disasters 16 ). COVID-19 restrictions that confined individuals to their local area also compelled them to focus their in-person efforts locally. Commentators on the initial lockdown in the UK remarked on extraordinary acts of generosity between individuals who belonged to the same community but were unknown to each other. However, research on adverse events also tells us that such community support is not necessarily maintained in the longer term. 16

Meanwhile, online forms of social support are not bound by geography, thus enabling interactions and social support to be received from a wider network of people. Formal online social support spaces (eg, support groups) existed well before COVID-19, but have vastly increased since. While online interactions can increase perceived social support, it is unclear whether remote communication technologies provide an effective substitute from in-person interaction during periods of social distancing. 17 18 It makes intuitive sense that the usefulness of online social support will vary by the type of support offered, degree of social interaction and ‘online communication skills’ of those taking part. Youth workers, for instance, have struggled to keep vulnerable youth engaged in online youth clubs, 19 despite others finding a positive association between amount of digital technology used by individuals during lockdown and perceived social support. 20 Other research has found that more frequent face-to-face contact and phone/video contact both related to lower levels of depression during the time period of March to August 2020, but the negative effect of a lack of contact was greater for those with higher levels of usual sociability. 21 Relatedly, important inequalities in social support exist, such that individuals who occupy more socially disadvantaged positions in society (eg, low socioeconomic status, older people) tend to have less access to social support, 22 potentially exacerbated by COVID-19.

Social and interactional norms

Interactional norms are key relational mechanisms which build trust, belonging and identity within and across groups in a system. Individuals in groups and societies apply meaning by ‘approving, arranging and redefining’ symbols of interaction. 23 A handshake, for instance, is a powerful symbol of trust and equality. Depending on context, not shaking hands may symbolise a failure to extend friendship, or a failure to reach agreement. The norms governing these symbols represent shared values and identity; and mutual understanding of these symbols enables individuals to achieve orderly interactions, establish supportive relationship accountability and connect socially. 24 25

Physical distancing measures to contain the spread of COVID-19 radically altered these norms of interaction, particularly those used to convey trust, affinity, empathy and respect (eg, hugging, physical comforting). 26 As epidemic waves rose and fell, the work to negotiate these norms required intense cognitive effort; previously taken-for-granted interactions were re-examined, factoring in current restriction levels, own and (assumed) others’ vulnerability and tolerance of risk. This created awkwardness, and uncertainty, for example, around how to bring closure to an in-person interaction or convey warmth. The instability in scripted ways of interacting created particular strain for individuals who already struggled to encode and decode interactions with others (eg, those who are deaf or have autism spectrum disorder); difficulties often intensified by mask wearing. 27

Large social gatherings—for example, weddings, school assemblies, sporting events—also present key opportunities for affirming and assimilating interactional norms, building cohesion and shared identity and facilitating cooperation across social groups. 28 Online ‘equivalents’ do not easily support ‘social-bonding’ activities such as singing and dancing, and rarely enable chance/spontaneous one-on-one conversations with peripheral/weaker network ties (see the Social networks section) which can help strengthen bonds across a larger network. The loss of large gatherings to celebrate rites of passage (eg, bar mitzvah, weddings) has additional relational costs since these events are performed by and for communities to reinforce belonging, and to assist in transitioning to new phases of life. 29 The loss of interaction with diverse others via community and large group gatherings also reduces intergroup contact, which may then tend towards more prejudiced outgroup attitudes. While online interaction can go some way to mimicking these interaction norms, there are key differences. A sense of anonymity, and lack of in-person emotional cues, tends to support norms of polarisation and aggression in expressing differences of opinion online. And while online platforms have potential to provide intergroup contact, the tendency of much social media to form homogeneous ‘echo chambers’ can serve to further reduce intergroup contact. 30 31

Intimacy relates to the feeling of emotional connection and closeness with other human beings. Emotional connection, through romantic, friendship or familial relationships, fulfils a basic human need 32 and strongly benefits health, including reduced stress levels, improved mental health, lowered blood pressure and reduced risk of heart disease. 32 33 Intimacy can be fostered through familiarity, feeling understood and feeling accepted by close others. 34

Intimacy via companionship and closeness is fundamental to mental well-being. Positively, the COVID-19 pandemic has offered opportunities for individuals to (re)connect and (re)strengthen close relationships within their household via quality time together, following closure of many usual external social activities. Research suggests that the first full UK lockdown period led to a net gain in the quality of steady relationships at a population level, 35 but amplified existing inequalities in relationship quality. 35 36 For some in single-person households, the absence of a companion became more conspicuous, leading to feelings of loneliness and lower mental well-being. 37 38 Additional pandemic-related relational strain 39 40 resulted, for some, in the initiation or intensification of domestic abuse. 41 42

Physical touch is another key aspect of intimacy, a fundamental human need crucial in maintaining and developing intimacy within close relationships. 34 Restrictions on social interactions severely restricted the number and range of people with whom physical affection was possible. The reduction in opportunity to give and receive affectionate physical touch was not experienced equally. Many of those living alone found themselves completely without physical contact for extended periods. The deprivation of physical touch is evidenced to take a heavy emotional toll. 43 Even in future, once physical expressions of affection can resume, new levels of anxiety over germs may introduce hesitancy into previously fluent blending of physical and verbal intimate social connections. 44

The pandemic also led to shifts in practices and norms around sexual relationship building and maintenance, as individuals adapted and sought alternative ways of enacting sexual intimacy. This too is important, given that intimate sexual activity has known benefits for health. 45 46 Given that social restrictions hinged on reducing household mixing, possibilities for partnered sexual activity were primarily guided by living arrangements. While those in cohabiting relationships could potentially continue as before, those who were single or in non-cohabiting relationships generally had restricted opportunities to maintain their sexual relationships. Pornography consumption and digital partners were reported to increase since lockdown. 47 However, online interactions are qualitatively different from in-person interactions and do not provide the same opportunities for physical intimacy.

Recommendations and conclusions

In the sections above we have outlined the ways in which COVID-19 has impacted social relationships, showing how relational mechanisms key to health have been undermined. While some of the damage might well self-repair after the pandemic, there are opportunities inherent in deliberative efforts to build back in ways that facilitate greater resilience in social and community relationships. We conclude by making three recommendations: one regarding public health responses to the pandemic; and two regarding social recovery.

Recommendation 1: explicitly count the relational cost of public health policies to control the pandemic

Effective handling of a pandemic recognises that social, economic and health concerns are intricately interwoven. It is clear that future research and policy attention must focus on the social consequences. As described above, policies which restrict physical mixing across households carry heavy and unequal relational costs. These include for individuals (eg, loss of intimate touch), dyads (eg, loss of warmth, comfort), networks (eg, restricted access to support) and communities (eg, loss of cohesion and identity). Such costs—and their unequal impact—should not be ignored in short-term efforts to control an epidemic. Some public health responses—restrictions on international holiday travel and highly efficient test and trace systems—have relatively small relational costs and should be prioritised. At a national level, an earlier move to proportionate restrictions, and investment in effective test and trace systems, may help prevent escalation of spread to the point where a national lockdown or tight restrictions became an inevitability. Where policies with relational costs are unavoidable, close attention should be paid to the unequal relational impact for those whose personal circumstances differ from normative assumptions of two adult families. This includes consideration of whether expectations are fair (eg, for those who live alone), whether restrictions on social events are equitable across age group, religious/ethnic groupings and social class, and also to ensure that the language promoted by such policies (eg, households; families) is not exclusionary. 48 49 Forethought to unequal impacts on social relationships should thus be integral to the work of epidemic preparedness teams.

Recommendation 2: intelligently balance online and offline ways of relating

A key ingredient for well-being is ‘getting together’ in a physical sense. This is fundamental to a human need for intimate touch, physical comfort, reinforcing interactional norms and providing practical support. Emerging evidence suggests that online ways of relating cannot simply replace physical interactions. But online interaction has many benefits and for some it offers connections that did not exist previously. In particular, online platforms provide new forms of support for those unable to access offline services because of mobility issues (eg, older people) or because they are geographically isolated from their support community (eg, lesbian, gay, bisexual, transgender and queer (LGBTQ) youth). Ultimately, multiple forms of online and offline social interactions are required to meet the needs of varying groups of people (eg, LGBTQ, older people). Future research and practice should aim to establish ways of using offline and online support in complementary and even synergistic ways, rather than veering between them as social restrictions expand and contract. Intelligent balancing of online and offline ways of relating also pertains to future policies on home and flexible working. A decision to switch to wholesale or obligatory homeworking should consider the risk to relational ‘group properties’ of the workplace community and their impact on employees’ well-being, focusing in particular on unequal impacts (eg, new vs established employees). Intelligent blending of online and in-person working is required to achieve flexibility while also nurturing supportive networks at work. Intelligent balance also implies strategies to build digital literacy and minimise digital exclusion, as well as coproducing solutions with intended beneficiaries.

Recommendation 3: build stronger and sustainable localised communities

In balancing offline and online ways of interacting, there is opportunity to capitalise on the potential for more localised, coherent communities due to scaled-down travel, homeworking and local focus that will ideally continue after restrictions end. There are potential economic benefits after the pandemic, such as increased trade as home workers use local resources (eg, coffee shops), but also relational benefits from stronger relationships around the orbit of the home and neighbourhood. Experience from previous crises shows that community volunteer efforts generated early on will wane over time in the absence of deliberate work to maintain them. Adequately funded partnerships between local government, third sector and community groups are required to sustain community assets that began as a direct response to the pandemic. Such partnerships could work to secure green spaces and indoor (non-commercial) meeting spaces that promote community interaction. Green spaces in particular provide a triple benefit in encouraging physical activity and mental health, as well as facilitating social bonding. 50 In building local communities, small community networks—that allow for diversity and break down ingroup/outgroup views—may be more helpful than the concept of ‘support bubbles’, which are exclusionary and less sustainable in the longer term. Rigorously designed intervention and evaluation—taking a systems approach—will be crucial in ensuring scale-up and sustainability.

The dramatic change to social interaction necessitated by efforts to control the spread of COVID-19 created stark challenges but also opportunities. Our essay highlights opportunities for learning, both to ensure the equity and humanity of physical restrictions, and to sustain the salutogenic effects of social relationships going forward. The starting point for capitalising on this learning is recognition of the disruption to relational mechanisms as a key part of the socioeconomic and health impact of the pandemic. In recovery planning, a general rule is that what is good for decreasing health inequalities (such as expanding social protection and public services and pursuing green inclusive growth strategies) 4 will also benefit relationships and safeguard relational mechanisms for future generations. Putting this into action will require political will.

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Twitter @karenmaxSPHSU, @Mark_McCann, @Rwilsonlowe, @KMitchinGlasgow

Contributors EL and KM led on the manuscript conceptualisation, review and editing. SP, KM, CB, RBP, RL, MM, JR, KS and RW-L contributed to drafting and revising the article. All authors assisted in revising the final draft.

Funding The research reported in this publication was supported by the Medical Research Council (MC_UU_00022/1, MC_UU_00022/3) and the Chief Scientist Office (SPHSU11, SPHSU14). EL is also supported by MRC Skills Development Fellowship Award (MR/S015078/1). KS and MM are also supported by a Medical Research Council Strategic Award (MC_PC_13027).

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

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I Thought We’d Learned Nothing From the Pandemic. I Wasn’t Seeing the Full Picture

M y first home had a back door that opened to a concrete patio with a giant crack down the middle. When my sister and I played, I made sure to stay on the same side of the divide as her, just in case. The 1988 film The Land Before Time was one of the first movies I ever saw, and the image of the earth splintering into pieces planted its roots in my brain. I believed that, even in my own backyard, I could easily become the tiny Triceratops separated from her family, on the other side of the chasm, as everything crumbled into chaos.

Some 30 years later, I marvel at the eerie, unexpected ways that cartoonish nightmare came to life – not just for me and my family, but for all of us. The landscape was already covered in fissures well before COVID-19 made its way across the planet, but the pandemic applied pressure, and the cracks broke wide open, separating us from each other physically and ideologically. Under the weight of the crisis, we scattered and landed on such different patches of earth we could barely see each other’s faces, even when we squinted. We disagreed viciously with each other, about how to respond, but also about what was true.

Recently, someone asked me if we’ve learned anything from the pandemic, and my first thought was a flat no. Nothing. There was a time when I thought it would be the very thing to draw us together and catapult us – as a capital “S” Society – into a kinder future. It’s surreal to remember those early days when people rallied together, sewing masks for health care workers during critical shortages and gathering on balconies in cities from Dallas to New York City to clap and sing songs like “Yellow Submarine.” It felt like a giant lightning bolt shot across the sky, and for one breath, we all saw something that had been hidden in the dark – the inherent vulnerability in being human or maybe our inescapable connectedness .

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But it turns out, it was just a flash. The goodwill vanished as quickly as it appeared. A couple of years later, people feel lied to, abandoned, and all on their own. I’ve felt my own curiosity shrinking, my willingness to reach out waning , my ability to keep my hands open dwindling. I look out across the landscape and see selfishness and rage, burnt earth and so many dead bodies. Game over. We lost. And if we’ve already lost, why try?

Still, the question kept nagging me. I wondered, am I seeing the full picture? What happens when we focus not on the collective society but at one face, one story at a time? I’m not asking for a bow to minimize the suffering – a pretty flourish to put on top and make the whole thing “worth it.” Yuck. That’s not what we need. But I wondered about deep, quiet growth. The kind we feel in our bodies, relationships, homes, places of work, neighborhoods.

Like a walkie-talkie message sent to my allies on the ground, I posted a call on my Instagram. What do you see? What do you hear? What feels possible? Is there life out here? Sprouting up among the rubble? I heard human voices calling back – reports of life, personal and specific. I heard one story at a time – stories of grief and distrust, fury and disappointment. Also gratitude. Discovery. Determination.

Among the most prevalent were the stories of self-revelation. Almost as if machines were given the chance to live as humans, people described blossoming into fuller selves. They listened to their bodies’ cues, recognized their desires and comforts, tuned into their gut instincts, and honored the intuition they hadn’t realized belonged to them. Alex, a writer and fellow disabled parent, found the freedom to explore a fuller version of herself in the privacy the pandemic provided. “The way I dress, the way I love, and the way I carry myself have both shrunk and expanded,” she shared. “I don’t love myself very well with an audience.” Without the daily ritual of trying to pass as “normal” in public, Tamar, a queer mom in the Netherlands, realized she’s autistic. “I think the pandemic helped me to recognize the mask,” she wrote. “Not that unmasking is easy now. But at least I know it’s there.” In a time of widespread suffering that none of us could solve on our own, many tended to our internal wounds and misalignments, large and small, and found clarity.

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I wonder if this flourishing of self-awareness is at least partially responsible for the life alterations people pursued. The pandemic broke open our personal notions of work and pushed us to reevaluate things like time and money. Lucy, a disabled writer in the U.K., made the hard decision to leave her job as a journalist covering Westminster to write freelance about her beloved disability community. “This work feels important in a way nothing else has ever felt,” she wrote. “I don’t think I’d have realized this was what I should be doing without the pandemic.” And she wasn’t alone – many people changed jobs , moved, learned new skills and hobbies, became politically engaged.

Perhaps more than any other shifts, people described a significant reassessment of their relationships. They set boundaries, said no, had challenging conversations. They also reconnected, fell in love, and learned to trust. Jeanne, a quilter in Indiana, got to know relatives she wouldn’t have connected with if lockdowns hadn’t prompted weekly family Zooms. “We are all over the map as regards to our belief systems,” she emphasized, “but it is possible to love people you don’t see eye to eye with on every issue.” Anna, an anti-violence advocate in Maine, learned she could trust her new marriage: “Life was not a honeymoon. But we still chose to turn to each other with kindness and curiosity.” So many bonds forged and broken, strengthened and strained.

Instead of relying on default relationships or institutional structures, widespread recalibrations allowed for going off script and fortifying smaller communities. Mara from Idyllwild, Calif., described the tangible plan for care enacted in her town. “We started a mutual-aid group at the beginning of the pandemic,” she wrote, “and it grew so quickly before we knew it we were feeding 400 of the 4000 residents.” She didn’t pretend the conditions were ideal. In fact, she expressed immense frustration with our collective response to the pandemic. Even so, the local group rallied and continues to offer assistance to their community with help from donations and volunteers (many of whom were originally on the receiving end of support). “I’ve learned that people thrive when they feel their connection to others,” she wrote. Clare, a teacher from the U.K., voiced similar conviction as she described a giant scarf she’s woven out of ribbons, each representing a single person. The scarf is “a collection of stories, moments and wisdom we are sharing with each other,” she wrote. It now stretches well over 1,000 feet.

A few hours into reading the comments, I lay back on my bed, phone held against my chest. The room was quiet, but my internal world was lighting up with firefly flickers. What felt different? Surely part of it was receiving personal accounts of deep-rooted growth. And also, there was something to the mere act of asking and listening. Maybe it connected me to humans before battle cries. Maybe it was the chance to be in conversation with others who were also trying to understand – what is happening to us? Underneath it all, an undeniable thread remained; I saw people peering into the mess and narrating their findings onto the shared frequency. Every comment was like a flare into the sky. I’m here! And if the sky is full of flares, we aren’t alone.

I recognized my own pandemic discoveries – some minor, others massive. Like washing off thick eyeliner and mascara every night is more effort than it’s worth; I can transform the mundane into the magical with a bedsheet, a movie projector, and twinkle lights; my paralyzed body can mother an infant in ways I’d never seen modeled for me. I remembered disappointing, bewildering conversations within my own family of origin and our imperfect attempts to remain close while also seeing things so differently. I realized that every time I get the weekly invite to my virtual “Find the Mumsies” call, with a tiny group of moms living hundreds of miles apart, I’m being welcomed into a pocket of unexpected community. Even though we’ve never been in one room all together, I’ve felt an uncommon kind of solace in their now-familiar faces.

Hope is a slippery thing. I desperately want to hold onto it, but everywhere I look there are real, weighty reasons to despair. The pandemic marks a stretch on the timeline that tangles with a teetering democracy, a deteriorating planet , the loss of human rights that once felt unshakable . When the world is falling apart Land Before Time style, it can feel trite, sniffing out the beauty – useless, firing off flares to anyone looking for signs of life. But, while I’m under no delusions that if we just keep trudging forward we’ll find our own oasis of waterfalls and grassy meadows glistening in the sunshine beneath a heavenly chorus, I wonder if trivializing small acts of beauty, connection, and hope actually cuts us off from resources essential to our survival. The group of abandoned dinosaurs were keeping each other alive and making each other laugh well before they made it to their fantasy ending.

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After the monarch butterfly went on the endangered-species list, my friend and fellow writer Hannah Soyer sent me wildflower seeds to plant in my yard. A simple act of big hope – that I will actually plant them, that they will grow, that a monarch butterfly will receive nourishment from whatever blossoms are able to push their way through the dirt. There are so many ways that could fail. But maybe the outcome wasn’t exactly the point. Maybe hope is the dogged insistence – the stubborn defiance – to continue cultivating moments of beauty regardless. There is value in the planting apart from the harvest.

I can’t point out a single collective lesson from the pandemic. It’s hard to see any great “we.” Still, I see the faces in my moms’ group, making pancakes for their kids and popping on between strings of meetings while we try to figure out how to raise these small people in this chaotic world. I think of my friends on Instagram tending to the selves they discovered when no one was watching and the scarf of ribbons stretching the length of more than three football fields. I remember my family of three, holding hands on the way up the ramp to the library. These bits of growth and rings of support might not be loud or right on the surface, but that’s not the same thing as nothing. If we only cared about the bottom-line defeats or sweeping successes of the big picture, we’d never plant flowers at all.

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Michael Cohen testifies in Trump hush money case

How to write about the impact of the coronavirus in a college essay.

The global impact of COVID-19, the disease caused by the novel coronavirus, means colleges and prospective students alike are in for an admissions cycle like no other. Both face unprecedented challenges and questions as they grapple with their respective futures amid the ongoing fallout of the pandemic.

Colleges must examine applicants without the aid of standardized test scores for many -- a factor that prompted many schools to go test-optional for now . Even grades, a significant component of a college application, may be hard to interpret with some high schools adopting pass-fail classes last spring due to the pandemic. Major college admissions factors are suddenly skewed.

"I can't help but think other (admissions) factors are going to matter more," says Ethan Sawyer, founder of the College Essay Guy, a website that offers free and paid essay-writing resources.

College essays and letters of recommendation , Sawyer says, are likely to carry more weight than ever in this admissions cycle. And many essays will likely focus on how the pandemic shaped students' lives throughout an often tumultuous 2020.

[ Read: How to Write a College Essay. ]

But before writing a college essay focused on the coronavirus, students should explore whether it's the best topic for them.

Writing About COVID-19 for a College Application

Much of daily life has been colored by the coronavirus. Virtual learning is the norm at many colleges and high schools, many extracurriculars have vanished and social lives have stalled for students complying with measures to stop the spread of COVID-19.

"For some young people, the pandemic took away what they envisioned as their senior year," says Robert Alexander, dean of admissions, financial aid and enrollment management at the University of Rochester in New York. "Maybe that's a spot on a varsity athletic team or the lead role in the fall play. And it's OK for them to mourn what should have been and what they feel like they lost, but more important is how are they making the most of the opportunities they do have?"

That question, Alexander says, is what colleges want answered if students choose to address COVID-19 in their college essay.

But the question of whether a student should write about the coronavirus is tricky. The answer depends largely on the student.

"In general, I don't think students should write about COVID-19 in their main personal statement for their application," Robin Miller, master college admissions counselor at IvyWise, a college counseling company, wrote in an email.

"Certainly, there may be exceptions to this based on a student's individual experience, but since the personal essay is the main place in the application where the student can really allow their voice to be heard and share insight into who they are as an individual, there are likely many other topics they can choose to write about that are more distinctive and unique than COVID-19," Miller says.

[ Read: What Colleges Look for: 6 Ways to Stand Out. ]

Opinions among admissions experts vary on whether to write about the likely popular topic of the pandemic.

"If your essay communicates something positive, unique, and compelling about you in an interesting and eloquent way, go for it," Carolyn Pippen, principal college admissions counselor at IvyWise, wrote in an email. She adds that students shouldn't be dissuaded from writing about a topic merely because it's common, noting that "topics are bound to repeat, no matter how hard we try to avoid it."

Above all, she urges honesty.

"If your experience within the context of the pandemic has been truly unique, then write about that experience, and the standing out will take care of itself," Pippen says. "If your experience has been generally the same as most other students in your context, then trying to find a unique angle can easily cross the line into exploiting a tragedy, or at least appearing as though you have."

But focusing entirely on the pandemic can limit a student to a single story and narrow who they are in an application, Sawyer says. "There are so many wonderful possibilities for what you can say about yourself outside of your experience within the pandemic."

He notes that passions, strengths, career interests and personal identity are among the multitude of essay topic options available to applicants and encourages them to probe their values to help determine the topic that matters most to them -- and write about it.

That doesn't mean the pandemic experience has to be ignored if applicants feel the need to write about it.

Writing About Coronavirus in Main and Supplemental Essays

Students can choose to write a full-length college essay on the coronavirus or summarize their experience in a shorter form.

To help students explain how the pandemic affected them, The Common App has added an optional section to address this topic. Applicants have 250 words to describe their pandemic experience and the personal and academic impact of COVID-19.

[ Read: The Common App: Everything You Need to Know. ]

"That's not a trick question, and there's no right or wrong answer," Alexander says. Colleges want to know, he adds, how students navigated the pandemic, how they prioritized their time, what responsibilities they took on and what they learned along the way.

If students can distill all of the above information into 250 words, there's likely no need to write about it in a full-length college essay, experts say. And applicants whose lives were not heavily altered by the pandemic may even choose to skip the optional COVID-19 question.

"This space is best used to discuss hardship and/or significant challenges that the student and/or the student's family experienced as a result of COVID-19 and how they have responded to those difficulties," Miller notes. Using the section to acknowledge a lack of impact, she adds, "could be perceived as trite and lacking insight, despite the good intentions of the applicant."

To guard against this lack of awareness, Sawyer encourages students to tap someone they trust to review their writing , whether it's the 250-word Common App response or the full-length essay.

Experts tend to agree that the short-form approach to this as an essay topic works better, but there are exceptions. And if a student does have a coronavirus story that he or she feels must be told, Alexander encourages the writer to be authentic in the essay.

"My advice for an essay about COVID-19 is the same as my advice about an essay for any topic -- and that is, don't write what you think we want to read or hear," Alexander says. "Write what really changed you and that story that now is yours and yours alone to tell."

Sawyer urges students to ask themselves, "What's the sentence that only I can write?" He also encourages students to remember that the pandemic is only a chapter of their lives and not the whole book.

Miller, who cautions against writing a full-length essay on the coronavirus, says that if students choose to do so they should have a conversation with their high school counselor about whether that's the right move. And if students choose to proceed with COVID-19 as a topic, she says they need to be clear, detailed and insightful about what they learned and how they adapted along the way.

"Approaching the essay in this manner will provide important balance while demonstrating personal growth and vulnerability," Miller says.

Pippen encourages students to remember that they are in an unprecedented time for college admissions.

"It is important to keep in mind with all of these (admission) factors that no colleges have ever had to consider them this way in the selection process, if at all," Pippen says. "They have had very little time to calibrate their evaluations of different application components within their offices, let alone across institutions. This means that colleges will all be handling the admissions process a little bit differently, and their approaches may even evolve over the course of the admissions cycle."

Searching for a college? Get our complete rankings of Best Colleges.

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How Science Beat the Virus

And what it lost in the process

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This article was published online on December 14, 2020.

In fall of 2019, exactly zero scientists were studying COVID‑19, because no one knew the disease existed. The coronavirus that causes it, SARS‑CoV‑2, had only recently jumped into humans and had been neither identified nor named. But by the end of March 2020, it had spread to more than 170 countries, sickened more than 750,000 people, and triggered the biggest pivot in the history of modern science. Thousands of researchers dropped whatever intellectual puzzles had previously consumed their curiosity and began working on the pandemic instead. In mere months, science became thoroughly COVID-ized.

As of this writing, the biomedical library PubMed lists more than 74,000 COVID-related scientific papers—more than twice as many as there are about polio, measles, cholera, dengue, or other diseases that have plagued humanity for centuries. Only 9,700 Ebola-related papers have been published since its discovery in 1976; last year, at least one journal received more COVID‑19 papers than that for consideration. By September, the prestigious New England Journal of Medicine had received 30,000 submissions—16,000 more than in all of 2019. “All that difference is COVID‑19,” Eric Rubin, NEJM ’s editor in chief, says. Francis Collins, the director of the National Institutes of Health, told me, “The way this has resulted in a shift in scientific priorities has been unprecedented.”

Much like famous initiatives such as the Manhattan Project and the Apollo program, epidemics focus the energies of large groups of scientists. In the U.S., the influenza pandemic of 1918, the threat of malaria in the tropical battlegrounds of World War II, and the rise of polio in the postwar years all triggered large pivots. Recent epidemics of Ebola and Zika each prompted a temporary burst of funding and publications . But “nothing in history was even close to the level of pivoting that’s happening right now,” Madhukar Pai of McGill University told me.

That’s partly because there are just more scientists: From 1960 to 2010, the number of biological or medical researchers in the U.S. increased sevenfold , from just 30,000 to more than 220,000. But SARS-CoV-2 has also spread farther and faster than any new virus in a century. For Western scientists, it wasn’t a faraway threat like Ebola. It threatened to inflame their lungs. It shut down their labs. “It hit us at home,” Pai said.

In a survey of 2,500 researchers in the U.S., Canada, and Europe, Kyle Myers from Harvard and his team found that 32 percent had shifted their focus toward the pandemic. Neuroscientists who study the sense of smell started investigating why COVID‑19 patients tend to lose theirs. Physicists who had previously experienced infectious diseases only by contracting them found themselves creating models to inform policy makers. Michael D. L. Johnson at the University of Arizona normally studies copper’s toxic effects on bacteria. But when he learned that SARS‑CoV‑2 persists for less time on copper surfaces than on other materials, he partially pivoted to see how the virus might be vulnerable to the metal. No other disease has been scrutinized so intensely, by so much combined intellect, in so brief a time.

These efforts have already paid off. New diagnostic tests can detect the virus within minutes. Massive open data sets of viral genomes and COVID‑19 cases have produced the most detailed picture yet of a new disease’s evolution. Vaccines are being developed with record-breaking speed. SARS‑CoV‑2 will be one of the most thoroughly characterized of all pathogens, and the secrets it yields will deepen our understanding of other viruses, leaving the world better prepared to face the next pandemic.

But the COVID‑19 pivot has also revealed the all-too-human frailties of the scientific enterprise . Flawed research made the pandemic more confusing, influencing misguided policies. Clinicians wasted millions of dollars on trials that were so sloppy as to be pointless. Overconfident poseurs published misleading work on topics in which they had no expertise. Racial and gender inequalities in the scientific field widened.

Amid a long winter of sickness , it’s hard not to focus on the political failures that led us to a third surge. But when people look back on this period, decades from now, they will also tell stories, both good and bad, about this extraordinary moment for science. At its best, science is a self-correcting march toward greater knowledge for the betterment of humanity. At its worst, it is a self-interested pursuit of greater prestige at the cost of truth and rigor. The pandemic brought both aspects to the fore. Humanity will benefit from the products of the COVID‑19 pivot. Science itself will too, if it learns from the experience.

In February, Jennifer Doudna, one of America’s most prominent scientists, was still focused on CRISPR—the gene-editing tool that she’d co-discovered and that won her a Nobel Prize in October. But when her son’s high school shut down and UC Berkeley, her university, closed its campus, the severity of the impending pandemic became clear. “In three weeks, I went from thinking we’re still okay to thinking that my whole life is going to change,” she told me. On March 13, she and dozens of colleagues at the Innovative Genomics Institute, which she leads, agreed to pause most of their ongoing projects and redirect their skills to addressing COVID‑19. They worked on CRISPR-based diagnostic tests. Because existing tests were in short supply, they converted lab space into a pop-up testing facility to serve the local community. “We need to make our expertise relevant to whatever is happening right now,” she said.

Scientists who’d already been studying other emerging diseases were even quicker off the mark. Lauren Gardner, an engineering professor at Johns Hopkins University who has studied dengue and Zika, knew that new epidemics are accompanied by a dearth of real-time data. So she and one of her students created an online global dashboard to map and tally all publicly reported COVID‑19 cases and deaths. After one night of work, they released it, on January 22. The dashboard has since been accessed daily by governments, public-health agencies, news organizations, and anxious citizens.

Studying deadly viruses is challenging at the best of times, and was especially so this past year. To handle SARS‑CoV‑2, scientists must work in “biosafety level 3” labs, fitted with special airflow systems and other extreme measures; although the actual number is not known, an estimated 200 such facilities exist in the U.S. Researchers often test new drugs and vaccines on monkeys before proceeding to human trials, but the U.S. is facing a monkey shortage after China stopped exporting the animals, possibly because it needed them for research. And other biomedical research is now more difficult because of physical-distancing requirements. “Usually we had people packed in, but with COVID, we do shift work,” Akiko Iwasaki, a Yale immunologist, told me. “People are coming in at ridiculous hours” to protect themselves from the very virus they are trying to study.

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Experts on emerging diseases are scarce: These threats go neglected by the public in the lulls between epidemics. “Just a year ago I had to explain to people why I was studying coronaviruses,” says Lisa Gralinski of the University of North Carolina at Chapel Hill. “That’s never going to be a concern again.” Stressed and stretched, she and other emerging-disease researchers were also conscripted into unfamiliar roles. They’re acting as makeshift advisers to businesses, schools, and local governments. They’re barraged by interview requests from journalists. They’re explaining the nuances of the pandemic on Twitter, to huge new follower counts. “It’s often the same person who’s helping the Namibian government to manage malaria outbreaks and is now being pulled into helping Maryland manage COVID‑19,” Gardner told me.

But the newfound global interest in viruses also means “you have a lot more people you can talk through problems with,” Pardis Sabeti, a computational geneticist at the Broad Institute of MIT and Harvard, told me. Indeed, COVID‑19 papers are more likely than typical biomedical studies to have authors who had never published together before, according to a team led by Ying Ding, who works at the University of Texas at Austin.

Fast-forming alliances could work at breakneck speed because many researchers had spent the past few decades transforming science from a plodding, cloistered endeavor into something nimbler and more transparent. Traditionally, a scientist submits her paper to a journal, which sends it to a (surprisingly small) group of peers for (several rounds of usually anonymous) comments; if the paper passes this (typically months-long) peer-review gantlet, it is published (often behind an expensive paywall). Languid and opaque, this system is ill-suited to a fast-moving outbreak. But biomedical scientists can now upload preliminary versions of their papers, or “preprints,” to freely accessible websites, allowing others to immediately dissect and build upon their results. This practice had been slowly gaining popularity before 2020, but proved so vital for sharing information about COVID‑19 that it will likely become a mainstay of modern biomedical research. Preprints accelerate science, and the pandemic accelerated the use of preprints. At the start of the year, one repository, medRxiv (pronounced “med archive”), held about 1,000 preprints. By the end of October, it had more than 12,000.

Open data sets and sophisticated new tools to manipulate them have likewise made today’s researchers more flexible. SARS‑CoV‑2’s genome was decoded and shared by Chinese scientists just 10 days after the first cases were reported. By November, more than 197,000 SARS‑CoV‑2 genomes had been sequenced. About 90 years ago, no one had even seen an individual virus; today, scientists have reconstructed the shape of SARS‑CoV‑2 down to the position of individual atoms. Researchers have begun to uncover how SARS‑CoV‑2 compares with other coronaviruses in wild bats, the likely reservoir; how it infiltrates and co-opts our cells; how the immune system overreacts to it, creating the symptoms of COVID‑19. “We’re learning about this virus faster than we’ve ever learned about any virus in history,” Sabeti said.

By March, the odds of quickly eradicating the new coronavirus looked slim. A vaccine became the likeliest endgame, and the race to create one was a resounding success. The process normally takes years, but as I write this, 54 different vaccines are being tested for safety and efficacy, and 12 have entered Phase 3 clinical trials—the final checkpoint. As of this writing, Pfizer/BioNTech and Moderna have announced that, based on preliminary results from these trials, their respective vaccines are roughly 95 percent effective at preventing COVID‑19. * “We went from a virus whose sequence was only known in January, and now in the fall, we’re finishing— finishing —a Phase 3 trial,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and a member of the White House’s coronavirus task force, told me. “Holy mackerel.”

Most vaccines comprise dead, weakened, or fragmented pathogens, and must be made from scratch whenever a new threat emerges. But over the past decade, the U.S. and other countries have moved away from this slow “one bug, one drug” approach. Instead, they’ve invested in so-called platform technologies, in which a standard chassis can be easily customized with different payloads that target new viruses. For example, the Pfizer/BioNTech and Moderna vaccines both consist of nanoparticles that contain pieces of SARS‑CoV‑2’s genetic material—its mRNA. When volunteers are injected with these particles, their cells use the mRNA to reconstruct a noninfectious fragment of the virus, allowing their immune system to prepare antibodies that neutralize it. No company has ever brought an mRNA vaccine to market before, but because the basic platform had already been refined, researchers could quickly repurpose it with SARS‑CoV‑2’s mRNA. Moderna got its vaccine into Phase 1 clinical trials on March 16, just 66 days after the new virus’s genome was first uploaded—far faster than any pre-COVID vaccine.

Meanwhile, companies compressed the process of vaccine development by running what would normally be sequential steps in parallel, while still checking for safety and efficacy. The federal government’s Operation Warp Speed, an effort to accelerate vaccine distribution, funded several companies at once—an unusual move. It preordered doses and invested in manufacturing facilities before trials were complete, reducing the risk for pharmaceutical companies looking to participate. Ironically, federal ineptitude at containing SARS‑CoV‑2 helped too. In the U.S., “the fact that the virus is everywhere makes it easier to gauge the performance of a vaccine,” says Natalie Dean of the University of Florida, who studies vaccine trials. “You can’t do a [Phase 3] vaccine trial in South Korea,” because the outbreak there is under control.

Read: How the pandemic will end

Vaccines will not immediately end the pandemic . Millions of doses will have to be manufactured, allocated, and distributed ; large numbers of Americans could refuse the vaccine ; and how long vaccine-induced immunity will last is still unclear. In the rosiest scenario, the Pfizer/BioNTech and Moderna vaccines are approved and smoothly rolled out over the next 12 months. By the end of the year, the U.S. achieves herd immunity, after which the virus struggles to find susceptible hosts. It still circulates, but outbreaks are sporadic and short-lived. Schools and businesses reopen. Families hug tightly and celebrate joyously over Thanksgiving and Christmas.

And the next time a mystery pathogen emerges, scientists hope to quickly slot its genetic material into proven platforms, and move the resulting vaccines through the same speedy pipelines that were developed during this pandemic. “I don’t think the world of vaccine development will ever be the same again,” says Nicole Lurie of the Coalition for Epidemic Preparedness Innovations.

As fast as the vaccine-development process was, it could have been faster. Despite the stakes, some pharmaceutical companies with relevant expertise chose not to enter the race, perhaps dissuaded by intense competition. Instead, from February to May, the sector roughly tripled its efforts to develop drugs to treat COVID‑19, according to Kevin Bryan, an economist at the University of Toronto. The decades-old steroid dexamethasone turned out to reduce death rates among severely ill patients on ventilators by more than 12 percent. Early hints suggest that newer treatments such as the monoclonal-antibody therapy bamlanivimab, which was just approved for emergency use by the FDA, could help newly infected patients who have not yet been hospitalized. But although these wins are significant, they are scarce. Most drugs haven’t been effective. Health-care workers became better at saving hospitalized patients more through improvements in basic medical care than through pharmaceutical panaceas—a predictable outcome, because antiviral drugs tend to offer only modest benefits.

The quest for COVID‑19 treatments was slowed by a torrent of shoddy studies whose results were meaningless at best and misleading at worst. Many of the thousands of clinical trials that were launched were too small to produce statistically solid results. Some lacked a control group—a set of comparable patients who received a placebo, and who provided a baseline against which the effects of a drug could be judged. Other trials needlessly overlapped. At least 227 involved hydroxychloroquine—the antimalarial drug that Donald Trump hyped for months. A few large trials eventually confirmed that hydroxychloroquine does nothing for COVID‑19 patients, but not before hundreds of thousands of people were recruited into pointlessly small studies . More than 100,000 Americans have also received convalescent plasma—another treatment that Trump touted. But because most were not enrolled in rigorous trials, “we still don’t know if it works—and it likely doesn’t,” says Luciana Borio, the former director for medical and biodefense preparedness at the National Security Council. “What a waste of time and resources.”

Read: How we survive the winter

In the heat of a disaster, when emergency rooms are filling and patients are dying, it is hard to set up one careful study, let alone coordinate several across a country. But coordination is not impossible. During World War II , federal agencies unified private companies, universities, the military, and other entities in a carefully orchestrated effort to speed pharmaceutical development from benchtop to battlefield. The results—revolutionary malaria treatments, new ways of mass-producing antibiotics, and at least 10 new or improved vaccines for influenza and other diseases—represented “not a triumph of scientific genius but rather of organizational purpose and efficiency,” Kendall Hoyt of Dartmouth College has written.

Similar triumphs occurred last year—in other countries. In March, taking advantage of the United Kingdom’s nationalized health system, British researchers launched a nationwide study called Recovery, which has since enrolled more than 17,600 COVID‑19 patients across 176 institutions. Recovery offered conclusive answers about dexamethasone and hydroxychloroquine and is set to weigh in on several other treatments. No other study has done more to shape the treatment of COVID‑19. The U.S. is now catching up. In April, the NIH launched a partnership called ACTIV , in which academic and industry scientists prioritized the most promising drugs and coordinated trial plans across the country. Since August, several such trials have started. This model was late, but is likely to outlast the pandemic itself, allowing future researchers to rapidly sort medical wheat from pharmaceutical chaff. “I can’t imagine we’ll go back to doing clinical research in the future the way we did in the past,” the NIH’s Francis Collins said.

Even after the COVID‑19 pandemic, the fruits of the pivot will leave us better equipped for our long and intensifying war against harmful viruses. The last time a virus caused this much devastation—the flu pandemic of 1918—scientists were only just learning about viruses, and spent time looking for a bacterial culprit. This one is different. With so many scientists observing intently as a virus wreaks its horrible work upon millions of bodies, the world is learning lessons that could change the way we think about these pathogens forevermore.

Consider the long-term consequences of viral infections. Years after the original SARS virus hit Hong Kong in 2003, about a quarter of survivors still had myalgic encephalomyelitis—a chronic illness whose symptoms, such as extreme fatigue and brain fogs, can worsen dramatically after mild exertion. ME cases are thought to be linked to viral infections, and clusters sometimes follow big outbreaks. So when SARS‑CoV‑2 started spreading, people with ME were unsurprised to hear that tens of thousands of COVID‑19 “long-haulers” were experiencing incapacitating symptoms that rolled on for months . “Everyone in my community has been thinking about this since the start of the pandemic,” says Jennifer Brea, the executive director of the advocacy group #MEAction.

ME and sister illnesses such as dysautonomia, fibromyalgia, and mast cell activation syndrome have long been neglected, their symptoms dismissed as imaginary or psychiatric. Research is poorly funded, so few scientists study them. Little is known about how to prevent and treat them. This negligence has left COVID‑19 long-haulers with few answers or options, and they initially endured the same dismissal as the larger ME community. But their sheer numbers have forced a degree of recognition. They started researching, cataloging their own symptoms. They gained audiences with the NIH and the World Health Organization. Patients who are themselves experts in infectious disease or public health published their stories in top journals. “Long COVID” is being taken seriously, and Brea hopes it might drag all post-infection illnesses into the spotlight. ME never experienced a pivot. COVID‑19 might inadvertently create one.

Anthony Fauci hopes so. His career was defined by HIV, and in 2019 he said in a paper he co-wrote that “the collateral advantages of” studying HIV “have been profound.” Research into HIV/AIDS revolutionized our understanding of the immune system and how diseases subvert it. It produced techniques for developing antiviral drugs that led to treatments for hepatitis C. Inactivated versions of HIV have been used to treat cancers and genetic disorders. From one disease came a cascade of benefits. COVID‑19 will be no different. Fauci had personally seen cases of prolonged symptoms after other viral infections, but “I didn’t really have a good scientific handle on it,” he told me. Such cases are hard to study, because it’s usually impossible to identify the instigating pathogen. But COVID‑19 has created “the most unusual situation imaginable,” Fauci said—a massive cohort of people with long-haul symptoms that are almost certainly caused by one known virus. “It’s an opportunity we cannot lose,” he said.

Read: The core lesson of the COVID-19 heart debate

COVID‑19 has developed a terrifying mystique because it seems to behave in unusual ways. It causes mild symptoms in some but critical illness in others. It is a respiratory virus and yet seems to attack the heart, brain, kidneys, and other organs. It has reinfected a small number of people who had recently recovered. But many other viruses share similar abilities; they just don’t infect millions of people in a matter of months or grab the attention of the entire scientific community. Thanks to COVID‑19, more researchers are looking for these rarer sides of viral infections, and spotting them.

At least 20 known viruses, including influenza and measles, can trigger myocarditis—inflammation of the heart. Some of these cases resolve on their own, but others cause persistent scarring, and still others rapidly progress into lethal problems. No one knows what proportion of people with viral myocarditis experience the most mild fate, because doctors typically notice only those who seek medical attention. But now researchers are also intently scrutinizing the hearts of people with mild or asymptomatic COVID‑19 infections, including college athletes, given concerns about sudden cardiac arrest during strenuous workouts. The lessons from these efforts could ultimately avert deaths from other infections.

Respiratory viruses, though extremely common, are often neglected. Respiratory syncytial virus, parainfluenza viruses, rhinoviruses, adenoviruses, bocaviruses, a quartet of other human coronaviruses—they mostly cause mild coldlike illnesses, but those can be severe. How often? Why? It’s hard to say, because, influenza aside, such viruses attract little funding or interest. “There’s a perception that they’re just colds and there’s nothing much to learn,” says Emily Martin of the University of Michigan, who has long struggled to get funding to study them. Such reasoning is shortsighted folly. Respiratory viruses are the pathogens most likely to cause pandemics, and those outbreaks could potentially be far worse than COVID‑19’s.

Read: We need to talk about ventilation

Their movements through the air have been poorly studied, too. “There’s this very entrenched idea,” says Linsey Marr at Virginia Tech, that viruses mostly spread through droplets (short-range globs of snot and spit) rather than aerosols (smaller, dustlike flecks that travel farther). That idea dates back to the 1930s, when scientists were upending outdated notions that disease was caused by “bad air,” or miasma. But the evidence that SARS‑CoV‑2 can spread through aerosols “is now overwhelming,” says Marr, one of the few scientists who, before the pandemic, studied how viruses spread through air. “I’ve seen more acceptance in the last six months than over the 12 years I’ve been working on this.”

Another pandemic is inevitable, but it will find a very different community of scientists than COVID‑19 did. They will immediately work to determine whether the pathogen—most likely another respiratory virus—moves through aerosols, and whether it spreads from infected people before causing symptoms. They might call for masks and better ventilation from the earliest moments, not after months of debate. They will anticipate the possibility of an imminent wave of long-haul symptoms, and hopefully discover ways of preventing them. They might set up research groups to prioritize the most promising drugs and coordinate large clinical trials. They might take vaccine platforms that worked best against COVID‑19, slot in the genetic material of the new pathogen, and have a vaccine ready within months.

For all its benefits, the single-minded focus on COVID‑19 will also leave a slew of negative legacies. Science is mostly a zero-sum game, and when one topic monopolizes attention and money, others lose out. Last year, between physical-distancing restrictions, redirected funds, and distracted scientists, many lines of research slowed to a crawl. Long-term studies that monitored bird migrations or the changing climate will forever have holes in their data because field research had to be canceled. Conservationists who worked to protect monkeys and apes kept their distance for fear of passing COVID‑19 to already endangered species. Roughly 80 percent of non-COVID‑19 clinical trials in the U.S.—likely worth billions of dollars—were interrupted or stopped because hospitals were overwhelmed and volunteers were stuck at home. Even research on other infectious diseases was back-burnered. “All the non-COVID work that I was working on before the pandemic started is now piling up and gathering dust,” says Angela Rasmussen of Georgetown University, who normally studies Ebola and MERS. “Those are still problems.”

The COVID‑19 pandemic is a singular disaster, and it is reasonable for society—and scientists—to prioritize it. But the pivot was driven by opportunism as much as altruism. Governments, philanthropies, and universities channeled huge sums toward COVID‑19 research. The NIH alone received nearly $3.6 billion from Congress. The Bill & Melinda Gates Foundation apportioned $350 million for COVID‑19 work. “Whenever there’s a big pot of money, there’s a feeding frenzy,” Madhukar Pai told me. He works on tuberculosis, which causes 1.5 million deaths a year—comparable to COVID‑19’s toll in 2020. Yet tuberculosis research has been mostly paused. None of Pai’s colleagues pivoted when Ebola or Zika struck, but “half of us have now swung to working on COVID‑19,” he said. “It’s a black hole, sucking us all in.”

While the most qualified experts became quickly immersed in the pandemic response, others were stuck at home looking for ways to contribute. Using the same systems that made science faster, they could download data from free databases, run quick analyses with intuitive tools, publish their work on preprint servers, and publicize it on Twitter. Often, they made things worse by swerving out of their scholarly lanes and plowing into unfamiliar territory. Nathan Ballantyne, a philosopher at Fordham University, calls this “ epistemic trespassing .” It can be a good thing: Continental drift was championed by Alfred Wegener, a meteorologist; microbes were first documented by Antonie van Leeuwenhoek, a draper. But more often than not, epistemic trespassing just creates a mess, especially when inexperience couples with overconfidence.

On March 28, a preprint noted that countries that universally use a tuberculosis vaccine called BCG had lower COVID‑19 mortality rates. But such cross-country comparisons are infamously treacherous. For example, countries with higher cigarette-usage rates have longer life expectancies, not because smoking prolongs life but because it is more popular in wealthier nations. This tendency to draw faulty conclusions about individual health using data about large geographical regions is called the ecological fallacy. Epidemiologists know to avoid it. The BCG-preprint authors, who were from an osteopathic college in New York, didn’t seem to . But their paper was covered by more than 70 news outlets, and dozens of inexperienced teams offered similarly specious analyses. “People who don’t know how to spell tuberculosis have told me they can solve the link between BCG and COVID‑19,” Pai said. “Someone told me they can do it in 48 hours with a hackathon.”

Other epistemic trespassers spent their time reinventing the wheel. One new study, published in NEJM , used lasers to show that when people speak, they release aerosols. But as the authors themselves note, the same result—sans lasers—was published in 1946, Marr says. I asked her whether any papers from the 2020 batch had taught her something new. After an uncomfortably long pause, she mentioned just one.

In some cases, bad papers helped shape the public narrative of the pandemic. On March 16, two biogeographers published a preprint arguing that COVID‑19 will “marginally affect the tropics” because it fares poorly in warm, humid conditions. Disease experts quickly noted that techniques like the ones the duo used are meant for modeling the geographic ranges of animal and plant species or vector-borne pathogens, and are ill-suited to simulating the spread of viruses like SARS-CoV-2. But their claim was picked up by more than 50 news outlets and echoed by the United Nations World Food Program. COVID‑19 has since run rampant in many tropical countries, including Brazil, Indonesia, and Colombia—and the preprint’s authors have qualified their conclusions in later versions of the paper. “It takes a certain type of person to think that weeks of reading papers gives them more perspective than someone with a Ph.D. on that subject, and that type of person has gotten a lot of airtime in this pandemic,” says Colin Carlson of Georgetown.

The incentives to trespass are substantial. Academia is a pyramid scheme: Each biomedical professor trains an average of six doctoral students across her career, but only 16 percent of the students get tenure-track positions . Competition is ferocious, and success hinges on getting published—a feat made easier by dramatic results. These factors pull researchers toward speed, short-termism, and hype at the expense of rigor—and the pandemic intensified that pull. With an anxious world crying out for information, any new paper could immediately draw international press coverage—and hundreds of citations.

The tsunami of rushed but dubious work made life harder for actual experts, who struggled to sift the signal from the noise. They also felt obliged to debunk spurious research in long Twitter threads and relentless media interviews—acts of public service that are rarely rewarded in academia. And they were overwhelmed by requests to peer-review new papers. Kristian Andersen, an infectious-disease researcher at Scripps Research, told me that journals used to send him two or three such requests a month. Now “I’m getting three or five a day,” he said in September.

The pandemic’s opportunities also fell inequitably upon the scientific community. In March, Congress awarded $75 million to the National Science Foundation to fast-track studies that could quickly contribute to the pandemic response. “That money just went ,” says Cassidy Sugimoto of Indiana University, who was on rotation at the agency at the time. “It was a first-come, first-served environment. It advantaged people who were aware of the system and could act upon it quickly.” But not all scientists could pivot to COVID‑19, or pivot with equal speed.

Among scientists, as in other fields, women do more child care, domestic work, and teaching than men, and are more often asked for emotional support by their students. These burdens increased as the pandemic took hold, leaving women scientists “less able to commit their time to learning about a new area of study, and less able to start a whole new research project,” says Molly M. King, a sociologist at Santa Clara University. Women’s research hours fell by nine percentage points more than did men’s because of the pressures of COVID‑19. And when COVID‑19 created new opportunities, men grabbed them more quickly. In the spring, the proportion of papers with women as first authors fell almost 44 percent in the preprint repository medRxiv, relative to 2019. And published COVID‑19 papers had 19 percent fewer women as first authors compared with papers from the same journals in the previous year. Men led more than 80 percent of national COVID‑19 task forces in 87 countries . Male scientists were quoted four times as frequently as female scientists in American news stories about the pandemic.

American scientists of color also found it harder to pivot than their white peers, because of unique challenges that sapped their time and energy. Black, Latino, and Indigenous scientists were most likely to have lost loved ones, adding mourning to their list of duties. Many grieved, too, after the killings of Breonna Taylor, George Floyd, Ahmaud Arbery, and others. They often faced questions from relatives who were mistrustful of the medical system, or were experiencing discriminatory care. They were suddenly tasked with helping their predominantly white institutions fight racism. Neil Lewis Jr. at Cornell, who studies racial health disparities, told me that many psychologists had long deemed his work irrelevant. “All of a sudden my inbox is drowning,” he said, while some of his own relatives have become ill and one has died.

Science suffers from the so-called Matthew effect, whereby small successes snowball into ever greater advantages, irrespective of merit. Similarly, early hindrances linger. Young researchers who could not pivot because they were too busy caring or grieving for others might suffer lasting consequences from an unproductive year. COVID‑19 “has really put the clock back in terms of closing the gap for women and underrepresented minorities,” Yale’s Akiko Iwasaki says. “Once we’re over the pandemic, we’ll need to fix it all again.”

COVID-19 has already changed science immensely, but if scientists are savvy, the most profound pivot is still to come—a grand reimagining of what medicine should be. In 1848, the Prussian government sent a young physician named Rudolf Virchow to investigate a typhus epidemic in Upper Silesia. Virchow didn’t know what caused the devastating disease, but he realized its spread was possible because of malnutrition, hazardous working conditions, crowded housing, poor sanitation, and the inattention of civil servants and aristocrats—problems that require social and political reforms. “Medicine is a social science,” Virchow said, “and politics is nothing but medicine in larger scale.”

This viewpoint fell by the wayside after germ theory became mainstream in the late 19th century. When scientists discovered the microbes responsible for tuberculosis, plague, cholera, dysentery, and syphilis, most fixated on these newly identified nemeses. Societal factors were seen as overly political distractions for researchers who sought to “be as ‘objective’ as possible,” says Elaine Hernandez, a medical sociologist at Indiana University. In the U.S., medicine fractured. New departments of sociology and cultural anthropology kept their eye on the societal side of health, while the nation’s first schools of public health focused instead on fights between germs and individuals. This rift widened as improvements in hygiene, living standards, nutrition, and sanitation lengthened life spans: The more social conditions improved, the more readily they could be ignored.

The ideological pivot away from social medicine began to reverse in the second half of the 20th century. The women’s-rights and civil-rights movements, the rise of environmentalism, and anti-war protests created a generation of scholars who questioned “the legitimacy, ideology, and practice of any science … that disregards social and economic inequality,” wrote Nancy Krieger of Harvard . Beginning in the 1980s, this new wave of social epidemiologists once again studied how poverty, privilege, and living conditions affect a person’s health—to a degree even Virchow hadn’t imagined. But as COVID‑19 has shown, the reintegration is not yet complete.

Politicians initially described COVID‑19 as a “great equalizer,” but when states began releasing demographic data, it was immediately clear that the disease was disproportionately infecting and killing people of color . These disparities aren’t biological. They stem from decades of discrimination and segregation that left minority communities in poorer neighborhoods with low-paying jobs, more health problems, and less access to health care—the same kind of problems that Virchow identified more than 170 years ago.

From the September 2020 issue: How the pandemic defeated America

Simple acts like wearing a mask and staying at home, which rely on people tolerating discomfort for the collective good, became society’s main defenses against the virus in the many months without effective drugs or vaccines. These are known as nonpharmaceutical interventions—a name that betrays medicine’s biological bias. For most of 2020, these were the only interventions on offer, but they were nonetheless defined in opposition to the more highly prized drugs and vaccines.

In March, when the U.S. started shutting down, one of the biggest questions on the mind of Whitney Robinson of UNC at Chapel Hill was: Are our kids going to be out of school for two years? While biomedical scientists tend to focus on sickness and recovery, social epidemiologists like her “think about critical periods that can affect the trajectory of your life,” she told me. Disrupting a child’s schooling at the wrong time can affect their entire career, so scientists should have prioritized research to figure out whether and how schools could reopen safely. But most studies on the spread of COVID‑19 in schools were neither large in scope nor well-designed enough to be conclusive. No federal agency funded a large, nationwide study, even though the federal government had months to do so. The NIH received billions for COVID‑19 research , but the National Institute of Child Health and Human Development—one of its 27 constituent institutes and centers—got nothing.

The horrors that Rudolf Virchow saw in Upper Silesia radicalized him, pushing the future “father of modern pathology” to advocate for social reforms. The current pandemic has affected scientists in the same way. Calm researchers became incensed as potentially game-changing innovations like cheap diagnostic tests were squandered by a negligent administration and a muzzled Centers for Disease Control and Prevention. Austere publications like NEJM and Nature published explicitly political editorials castigating the Trump administration for its failures and encouraging voters to hold the president accountable. COVID‑19 could be the catalyst that fully reunifies the social and biological sides of medicine, bridging disciplines that have been separated for too long.

“To study COVID‑19 is not only to study the disease itself as a biological entity,” says Alondra Nelson, the president of the Social Science Research Council. “What looks like a single problem is actually all things, all at once. So what we’re actually studying is literally everything in society, at every scale, from supply chains to individual relationships.”

The scientific community spent the pre-pandemic years designing faster ways of doing experiments, sharing data, and developing vaccines, allowing it to mobilize quickly when COVID‑19 emerged. Its goal now should be to address its many lingering weaknesses. Warped incentives, wasteful practices, overconfidence, inequality, a biomedical bias—COVID‑19 has exposed them all. And in doing so, it offers the world of science a chance to practice one of its most important qualities: self-correction.

* The print version of this article stated that the Moderna and Pfizer/BioNTech vaccines were reported to be 95 percent effective at preventing COVID-19 infections. In fact, the vaccines prevent disease, not infection.

This article appears in the January/February 2021 print edition with the headline “The COVID-19 Manhattan Project.”

How to Write About the Impact of the Coronavirus in a College Essay

U.S. News & World Report

October 21, 2020, 12:00 AM

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The global impact of COVID-19, the disease caused by the novel coronavirus, means colleges and prospective students alike are in for an admissions cycle like no other. Both face unprecedented challenges and questions as they grapple with their respective futures amid the ongoing fallout of the pandemic.

Colleges must examine applicants without the aid of standardized test scores for many — a factor that prompted many schools to go test-optional for now . Even grades, a significant component of a college application, may be hard to interpret with some high schools adopting pass-fail classes last spring due to the pandemic. Major college admissions factors are suddenly skewed.

“I can’t help but think other (admissions) factors are going to matter more,” says Ethan Sawyer, founder of the College Essay Guy, a website that offers free and paid essay-writing resources.

College essays and letters of recommendation , Sawyer says, are likely to carry more weight than ever in this admissions cycle. And many essays will likely focus on how the pandemic shaped students’ lives throughout an often tumultuous 2020.

[ Read: How to Write a College Essay. ]

But before writing a college essay focused on the coronavirus, students should explore whether it’s the best topic for them.

Writing About COVID-19 for a College Application

Much of daily life has been colored by the coronavirus. Virtual learning is the norm at many colleges and high schools, many extracurriculars have vanished and social lives have stalled for students complying with measures to stop the spread of COVID-19.

“For some young people, the pandemic took away what they envisioned as their senior year,” says Robert Alexander, dean of admissions, financial aid and enrollment management at the University of Rochester in New York. “Maybe that’s a spot on a varsity athletic team or the lead role in the fall play. And it’s OK for them to mourn what should have been and what they feel like they lost, but more important is how are they making the most of the opportunities they do have?”

That question, Alexander says, is what colleges want answered if students choose to address COVID-19 in their college essay.

But the question of whether a student should write about the coronavirus is tricky. The answer depends largely on the student.

“In general, I don’t think students should write about COVID-19 in their main personal statement for their application,” Robin Miller, master college admissions counselor at IvyWise, a college counseling company, wrote in an email.

“Certainly, there may be exceptions to this based on a student’s individual experience, but since the personal essay is the main place in the application where the student can really allow their voice to be heard and share insight into who they are as an individual, there are likely many other topics they can choose to write about that are more distinctive and unique than COVID-19,” Miller says.

[ Read: What Colleges Look for: 6 Ways to Stand Out. ]

Opinions among admissions experts vary on whether to write about the likely popular topic of the pandemic.

“If your essay communicates something positive, unique, and compelling about you in an interesting and eloquent way, go for it,” Carolyn Pippen, principal college admissions counselor at IvyWise, wrote in an email. She adds that students shouldn’t be dissuaded from writing about a topic merely because it’s common, noting that “topics are bound to repeat, no matter how hard we try to avoid it.”

Above all, she urges honesty.

“If your experience within the context of the pandemic has been truly unique, then write about that experience, and the standing out will take care of itself,” Pippen says. “If your experience has been generally the same as most other students in your context, then trying to find a unique angle can easily cross the line into exploiting a tragedy, or at least appearing as though you have.”

But focusing entirely on the pandemic can limit a student to a single story and narrow who they are in an application, Sawyer says. “There are so many wonderful possibilities for what you can say about yourself outside of your experience within the pandemic.”

He notes that passions, strengths, career interests and personal identity are among the multitude of essay topic options available to applicants and encourages them to probe their values to help determine the topic that matters most to them — and write about it.

That doesn’t mean the pandemic experience has to be ignored if applicants feel the need to write about it.

Writing About Coronavirus in Main and Supplemental Essays

Students can choose to write a full-length college essay on the coronavirus or summarize their experience in a shorter form.

To help students explain how the pandemic affected them, The Common App has added an optional section to address this topic. Applicants have 250 words to describe their pandemic experience and the personal and academic impact of COVID-19.

[ Read: The Common App: Everything You Need to Know. ]

“That’s not a trick question, and there’s no right or wrong answer,” Alexander says. Colleges want to know, he adds, how students navigated the pandemic, how they prioritized their time, what responsibilities they took on and what they learned along the way.

If students can distill all of the above information into 250 words, there’s likely no need to write about it in a full-length college essay, experts say. And applicants whose lives were not heavily altered by the pandemic may even choose to skip the optional COVID-19 question.

“This space is best used to discuss hardship and/or significant challenges that the student and/or the student’s family experienced as a result of COVID-19 and how they have responded to those difficulties,” Miller notes. Using the section to acknowledge a lack of impact, she adds, “could be perceived as trite and lacking insight, despite the good intentions of the applicant.”

To guard against this lack of awareness, Sawyer encourages students to tap someone they trust to review their writing , whether it’s the 250-word Common App response or the full-length essay.

Experts tend to agree that the short-form approach to this as an essay topic works better, but there are exceptions. And if a student does have a coronavirus story that he or she feels must be told, Alexander encourages the writer to be authentic in the essay.

“My advice for an essay about COVID-19 is the same as my advice about an essay for any topic — and that is, don’t write what you think we want to read or hear,” Alexander says. “Write what really changed you and that story that now is yours and yours alone to tell.”

Sawyer urges students to ask themselves, “What’s the sentence that only I can write?” He also encourages students to remember that the pandemic is only a chapter of their lives and not the whole book.

Miller, who cautions against writing a full-length essay on the coronavirus, says that if students choose to do so they should have a conversation with their high school counselor about whether that’s the right move. And if students choose to proceed with COVID-19 as a topic, she says they need to be clear, detailed and insightful about what they learned and how they adapted along the way.

“Approaching the essay in this manner will provide important balance while demonstrating personal growth and vulnerability,” Miller says.

Pippen encourages students to remember that they are in an unprecedented time for college admissions.

“It is important to keep in mind with all of these (admission) factors that no colleges have ever had to consider them this way in the selection process, if at all,” Pippen says. “They have had very little time to calibrate their evaluations of different application components within their offices, let alone across institutions. This means that colleges will all be handling the admissions process a little bit differently, and their approaches may even evolve over the course of the admissions cycle.”

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How to Write About the Impact of the Coronavirus in a College Essay originally appeared on usnews.com

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Related categories:.

• Research article
• Open access
• Published: 04 June 2021

Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

• Israel Júnior Borges do Nascimento 1 , 2 ,
• Dónal P. O’Mathúna 3 , 4 ,
• Thilo Caspar von Groote 5 ,
• Hebatullah Mohamed Abdulazeem 6 ,
• Ishanka Weerasekara 7 , 8 ,
• Ana Marusic 9 ,
• Livia Puljak   ORCID: orcid.org/0000-0002-8467-6061 10 ,
• Vinicius Tassoni Civile 11 ,
• Irena Zakarija-Grkovic 9 ,
• Tina Poklepovic Pericic 9 ,
• Alvaro Nagib Atallah 11 ,
• Santino Filoso 12 ,
• Nicola Luigi Bragazzi 13 &
• Milena Soriano Marcolino 1

On behalf of the International Network of Coronavirus Disease 2019 (InterNetCOVID-19)

BMC Infectious Diseases volume  21 , Article number:  525 ( 2021 ) Cite this article

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Navigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Nine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes.

Eighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%.

Conclusions

In this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

Peer Review reports

The spread of the “Severe Acute Respiratory Coronavirus 2” (SARS-CoV-2), the causal agent of COVID-19, was characterized as a pandemic by the World Health Organization (WHO) in March 2020 and has triggered an international public health emergency [ 1 ]. The numbers of confirmed cases and deaths due to COVID-19 are rapidly escalating, counting in millions [ 2 ], causing massive economic strain, and escalating healthcare and public health expenses [ 3 , 4 ].

The research community has responded by publishing an impressive number of scientific reports related to COVID-19. The world was alerted to the new disease at the beginning of 2020 [ 1 ], and by mid-March 2020, more than 2000 articles had been published on COVID-19 in scholarly journals, with 25% of them containing original data [ 5 ]. The living map of COVID-19 evidence, curated by the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), contained more than 40,000 records by February 2021 [ 6 ]. More than 100,000 records on PubMed were labeled as “SARS-CoV-2 literature, sequence, and clinical content” by February 2021 [ 7 ].

Due to publication speed, the research community has voiced concerns regarding the quality and reproducibility of evidence produced during the COVID-19 pandemic, warning of the potential damaging approach of “publish first, retract later” [ 8 ]. It appears that these concerns are not unfounded, as it has been reported that COVID-19 articles were overrepresented in the pool of retracted articles in 2020 [ 9 ]. These concerns about inadequate evidence are of major importance because they can lead to poor clinical practice and inappropriate policies [ 10 ].

Systematic reviews are a cornerstone of today’s evidence-informed decision-making. By synthesizing all relevant evidence regarding a particular topic, systematic reviews reflect the current scientific knowledge. Systematic reviews are considered to be at the highest level in the hierarchy of evidence and should be used to make informed decisions. However, with high numbers of systematic reviews of different scope and methodological quality being published, overviews of multiple systematic reviews that assess their methodological quality are essential [ 11 , 12 , 13 ]. An overview of systematic reviews helps identify and organize the literature and highlights areas of priority in decision-making.

In this overview of systematic reviews, we aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.

Methodology

Research question.

This overview’s primary objective was to summarize and critically appraise systematic reviews that assessed any type of primary clinical data from patients infected with SARS-CoV-2. Our research question was purposefully broad because we wanted to analyze as many systematic reviews as possible that were available early following the COVID-19 outbreak.

Study design

We conducted an overview of systematic reviews. The idea for this overview originated in a protocol for a systematic review submitted to PROSPERO (CRD42020170623), which indicated a plan to conduct an overview.

Overviews of systematic reviews use explicit and systematic methods for searching and identifying multiple systematic reviews addressing related research questions in the same field to extract and analyze evidence across important outcomes. Overviews of systematic reviews are in principle similar to systematic reviews of interventions, but the unit of analysis is a systematic review [ 14 , 15 , 16 ].

We used the overview methodology instead of other evidence synthesis methods to allow us to collate and appraise multiple systematic reviews on this topic, and to extract and analyze their results across relevant topics [ 17 ]. The overview and meta-analysis of systematic reviews allowed us to investigate the methodological quality of included studies, summarize results, and identify specific areas of available or limited evidence, thereby strengthening the current understanding of this novel disease and guiding future research [ 13 ].

A reporting guideline for overviews of reviews is currently under development, i.e., Preferred Reporting Items for Overviews of Reviews (PRIOR) [ 18 ]. As the PRIOR checklist is still not published, this study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 statement [ 19 ]. The methodology used in this review was adapted from the Cochrane Handbook for Systematic Reviews of Interventions and also followed established methodological considerations for analyzing existing systematic reviews [ 14 ].

Approval of a research ethics committee was not necessary as the study analyzed only publicly available articles.

Eligibility criteria

Systematic reviews were included if they analyzed primary data from patients infected with SARS-CoV-2 as confirmed by RT-PCR or another pre-specified diagnostic technique. Eligible reviews covered all topics related to COVID-19 including, but not limited to, those that reported clinical symptoms, diagnostic methods, therapeutic interventions, laboratory findings, or radiological results. Both full manuscripts and abbreviated versions, such as letters, were eligible.

No restrictions were imposed on the design of the primary studies included within the systematic reviews, the last search date, whether the review included meta-analyses or language. Reviews related to SARS-CoV-2 and other coronaviruses were eligible, but from those reviews, we analyzed only data related to SARS-CoV-2.

No consensus definition exists for a systematic review [ 20 ], and debates continue about the defining characteristics of a systematic review [ 21 ]. Cochrane’s guidance for overviews of reviews recommends setting pre-established criteria for making decisions around inclusion [ 14 ]. That is supported by a recent scoping review about guidance for overviews of systematic reviews [ 22 ].

Thus, for this study, we defined a systematic review as a research report which searched for primary research studies on a specific topic using an explicit search strategy, had a detailed description of the methods with explicit inclusion criteria provided, and provided a summary of the included studies either in narrative or quantitative format (such as a meta-analysis). Cochrane and non-Cochrane systematic reviews were considered eligible for inclusion, with or without meta-analysis, and regardless of the study design, language restriction and methodology of the included primary studies. To be eligible for inclusion, reviews had to be clearly analyzing data related to SARS-CoV-2 (associated or not with other viruses). We excluded narrative reviews without those characteristics as these are less likely to be replicable and are more prone to bias.

Scoping reviews and rapid reviews were eligible for inclusion in this overview if they met our pre-defined inclusion criteria noted above. We included reviews that addressed SARS-CoV-2 and other coronaviruses if they reported separate data regarding SARS-CoV-2.

Information sources

Nine databases were searched for eligible records published between December 1, 2019, and March 24, 2020: Cochrane Database of Systematic Reviews via Cochrane Library, PubMed, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Sciences, LILACS (Latin American and Caribbean Health Sciences Literature), PDQ-Evidence, WHO’s Global Research on Coronavirus Disease (COVID-19), and Epistemonikos.

The comprehensive search strategy for each database is provided in Additional file 1 and was designed and conducted in collaboration with an information specialist. All retrieved records were primarily processed in EndNote, where duplicates were removed, and records were then imported into the Covidence platform [ 23 ]. In addition to database searches, we screened reference lists of reviews included after screening records retrieved via databases.

Study selection

All searches, screening of titles and abstracts, and record selection, were performed independently by two investigators using the Covidence platform [ 23 ]. Articles deemed potentially eligible were retrieved for full-text screening carried out independently by two investigators. Discrepancies at all stages were resolved by consensus. During the screening, records published in languages other than English were translated by a native/fluent speaker.

Data collection process

We custom designed a data extraction table for this study, which was piloted by two authors independently. Data extraction was performed independently by two authors. Conflicts were resolved by consensus or by consulting a third researcher.

We extracted the following data: article identification data (authors’ name and journal of publication), search period, number of databases searched, population or settings considered, main results and outcomes observed, and number of participants. From Web of Science (Clarivate Analytics, Philadelphia, PA, USA), we extracted journal rank (quartile) and Journal Impact Factor (JIF).

We categorized the following as primary outcomes: all-cause mortality, need for and length of mechanical ventilation, length of hospitalization (in days), admission to intensive care unit (yes/no), and length of stay in the intensive care unit.

The following outcomes were categorized as exploratory: diagnostic methods used for detection of the virus, male to female ratio, clinical symptoms, pharmacological and non-pharmacological interventions, laboratory findings (full blood count, liver enzymes, C-reactive protein, d-dimer, albumin, lipid profile, serum electrolytes, blood vitamin levels, glucose levels, and any other important biomarkers), and radiological findings (using radiography, computed tomography, magnetic resonance imaging or ultrasound).

We also collected data on reporting guidelines and requirements for the publication of systematic reviews and meta-analyses from journal websites where included reviews were published.

Quality assessment in individual reviews

Two researchers independently assessed the reviews’ quality using the “A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2)”. We acknowledge that the AMSTAR 2 was created as “a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions, or both” [ 24 ]. However, since AMSTAR 2 was designed for systematic reviews of intervention trials, and we included additional types of systematic reviews, we adjusted some AMSTAR 2 ratings and reported these in Additional file 2 .

Adherence to each item was rated as follows: yes, partial yes, no, or not applicable (such as when a meta-analysis was not conducted). The overall confidence in the results of the review is rated as “critically low”, “low”, “moderate” or “high”, according to the AMSTAR 2 guidance based on seven critical domains, which are items 2, 4, 7, 9, 11, 13, 15 as defined by AMSTAR 2 authors [ 24 ]. We reported our adherence ratings for transparency of our decision with accompanying explanations, for each item, in each included review.

One of the included systematic reviews was conducted by some members of this author team [ 25 ]. This review was initially assessed independently by two authors who were not co-authors of that review to prevent the risk of bias in assessing this study.

Synthesis of results

For data synthesis, we prepared a table summarizing each systematic review. Graphs illustrating the mortality rate and clinical symptoms were created. We then prepared a narrative summary of the methods, findings, study strengths, and limitations.

For analysis of the prevalence of clinical outcomes, we extracted data on the number of events and the total number of patients to perform proportional meta-analysis using RStudio© software, with the “meta” package (version 4.9–6), using the “metaprop” function for reviews that did not perform a meta-analysis, excluding case studies because of the absence of variance. For reviews that did not perform a meta-analysis, we presented pooled results of proportions with their respective confidence intervals (95%) by the inverse variance method with a random-effects model, using the DerSimonian-Laird estimator for τ 2 . We adjusted data using Freeman-Tukey double arcosen transformation. Confidence intervals were calculated using the Clopper-Pearson method for individual studies. We created forest plots using the RStudio© software, with the “metafor” package (version 2.1–0) and “forest” function.

Managing overlapping systematic reviews

Some of the included systematic reviews that address the same or similar research questions may include the same primary studies in overviews. Including such overlapping reviews may introduce bias when outcome data from the same primary study are included in the analyses of an overview multiple times. Thus, in summaries of evidence, multiple-counting of the same outcome data will give data from some primary studies too much influence [ 14 ]. In this overview, we did not exclude overlapping systematic reviews because, according to Cochrane’s guidance, it may be appropriate to include all relevant reviews’ results if the purpose of the overview is to present and describe the current body of evidence on a topic [ 14 ]. To avoid any bias in summary estimates associated with overlapping reviews, we generated forest plots showing data from individual systematic reviews, but the results were not pooled because some primary studies were included in multiple reviews.

Our search retrieved 1063 publications, of which 175 were duplicates. Most publications were excluded after the title and abstract analysis ( n = 860). Among the 28 studies selected for full-text screening, 10 were excluded for the reasons described in Additional file 3 , and 18 were included in the final analysis (Fig. 1 ) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Reference list screening did not retrieve any additional systematic reviews.

PRISMA flow diagram

Characteristics of included reviews

Summary features of 18 systematic reviews are presented in Table 1 . They were published in 14 different journals. Only four of these journals had specific requirements for systematic reviews (with or without meta-analysis): European Journal of Internal Medicine, Journal of Clinical Medicine, Ultrasound in Obstetrics and Gynecology, and Clinical Research in Cardiology . Two journals reported that they published only invited reviews ( Journal of Medical Virology and Clinica Chimica Acta ). Three systematic reviews in our study were published as letters; one was labeled as a scoping review and another as a rapid review (Table 2 ).

All reviews were published in English, in first quartile (Q1) journals, with JIF ranging from 1.692 to 6.062. One review was empty, meaning that its search did not identify any relevant studies; i.e., no primary studies were included [ 36 ]. The remaining 17 reviews included 269 unique studies; the majority ( N = 211; 78%) were included in only a single review included in our study (range: 1 to 12). Primary studies included in the reviews were published between December 2019 and March 18, 2020, and comprised case reports, case series, cohorts, and other observational studies. We found only one review that included randomized clinical trials [ 38 ]. In the included reviews, systematic literature searches were performed from 2019 (entire year) up to March 9, 2020. Ten systematic reviews included meta-analyses. The list of primary studies found in the included systematic reviews is shown in Additional file 4 , as well as the number of reviews in which each primary study was included.

Population and study designs

Most of the reviews analyzed data from patients with COVID-19 who developed pneumonia, acute respiratory distress syndrome (ARDS), or any other correlated complication. One review aimed to evaluate the effectiveness of using surgical masks on preventing transmission of the virus [ 36 ], one review was focused on pediatric patients [ 34 ], and one review investigated COVID-19 in pregnant women [ 37 ]. Most reviews assessed clinical symptoms, laboratory findings, or radiological results.

Systematic review findings

The summary of findings from individual reviews is shown in Table 2 . Overall, all-cause mortality ranged from 0.3 to 13.9% (Fig. 2 ).

A meta-analysis of the prevalence of mortality

Clinical symptoms

Seven reviews described the main clinical manifestations of COVID-19 [ 26 , 28 , 29 , 34 , 35 , 39 , 41 ]. Three of them provided only a narrative discussion of symptoms [ 26 , 34 , 35 ]. In the reviews that performed a statistical analysis of the incidence of different clinical symptoms, symptoms in patients with COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%), gastrointestinal disorders, such as diarrhea, nausea or vomiting (5.0–9.0%), and others (including, in one study only: dizziness 12.1%) (Figs. 3 , 4 , 5 , 6 , 7 , 8 and 9 ). Three reviews assessed cough with and without sputum together; only one review assessed sputum production itself (28.5%).

A meta-analysis of the prevalence of fever

A meta-analysis of the prevalence of cough

A meta-analysis of the prevalence of dyspnea

A meta-analysis of the prevalence of fatigue or myalgia

A meta-analysis of the prevalence of headache

A meta-analysis of the prevalence of gastrointestinal disorders

A meta-analysis of the prevalence of sore throat

Diagnostic aspects

Three reviews described methodologies, protocols, and tools used for establishing the diagnosis of COVID-19 [ 26 , 34 , 38 ]. The use of respiratory swabs (nasal or pharyngeal) or blood specimens to assess the presence of SARS-CoV-2 nucleic acid using RT-PCR assays was the most commonly used diagnostic method mentioned in the included studies. These diagnostic tests have been widely used, but their precise sensitivity and specificity remain unknown. One review included a Chinese study with clinical diagnosis with no confirmation of SARS-CoV-2 infection (patients were diagnosed with COVID-19 if they presented with at least two symptoms suggestive of COVID-19, together with laboratory and chest radiography abnormalities) [ 34 ].

Therapeutic possibilities

Pharmacological and non-pharmacological interventions (supportive therapies) used in treating patients with COVID-19 were reported in five reviews [ 25 , 27 , 34 , 35 , 38 ]. Antivirals used empirically for COVID-19 treatment were reported in seven reviews [ 25 , 27 , 34 , 35 , 37 , 38 , 41 ]; most commonly used were protease inhibitors (lopinavir, ritonavir, darunavir), nucleoside reverse transcriptase inhibitor (tenofovir), nucleotide analogs (remdesivir, galidesivir, ganciclovir), and neuraminidase inhibitors (oseltamivir). Umifenovir, a membrane fusion inhibitor, was investigated in two studies [ 25 , 35 ]. Possible supportive interventions analyzed were different types of oxygen supplementation and breathing support (invasive or non-invasive ventilation) [ 25 ]. The use of antibiotics, both empirically and to treat secondary pneumonia, was reported in six studies [ 25 , 26 , 27 , 34 , 35 , 38 ]. One review specifically assessed evidence on the efficacy and safety of the anti-malaria drug chloroquine [ 27 ]. It identified 23 ongoing trials investigating the potential of chloroquine as a therapeutic option for COVID-19, but no verifiable clinical outcomes data. The use of mesenchymal stem cells, antifungals, and glucocorticoids were described in four reviews [ 25 , 34 , 35 , 38 ].

Laboratory and radiological findings

Of the 18 reviews included in this overview, eight analyzed laboratory parameters in patients with COVID-19 [ 25 , 29 , 30 , 32 , 33 , 34 , 35 , 39 ]; elevated C-reactive protein levels, associated with lymphocytopenia, elevated lactate dehydrogenase, as well as slightly elevated aspartate and alanine aminotransferase (AST, ALT) were commonly described in those eight reviews. Lippi et al. assessed cardiac troponin I (cTnI) [ 25 ], procalcitonin [ 32 ], and platelet count [ 33 ] in COVID-19 patients. Elevated levels of procalcitonin [ 32 ] and cTnI [ 30 ] were more likely to be associated with a severe disease course (requiring intensive care unit admission and intubation). Furthermore, thrombocytopenia was frequently observed in patients with complicated COVID-19 infections [ 33 ].

Chest imaging (chest radiography and/or computed tomography) features were assessed in six reviews, all of which described a frequent pattern of local or bilateral multilobar ground-glass opacity [ 25 , 34 , 35 , 39 , 40 , 41 ]. Those six reviews showed that septal thickening, bronchiectasis, pleural and cardiac effusions, halo signs, and pneumothorax were observed in patients suffering from COVID-19.

Quality of evidence in individual systematic reviews

Table 3 shows the detailed results of the quality assessment of 18 systematic reviews, including the assessment of individual items and summary assessment. A detailed explanation for each decision in each review is available in Additional file 5 .

Using AMSTAR 2 criteria, confidence in the results of all 18 reviews was rated as “critically low” (Table 3 ). Common methodological drawbacks were: omission of prospective protocol submission or publication; use of inappropriate search strategy: lack of independent and dual literature screening and data-extraction (or methodology unclear); absence of an explanation for heterogeneity among the studies included; lack of reasons for study exclusion (or rationale unclear).

Risk of bias assessment, based on a reported methodological tool, and quality of evidence appraisal, in line with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, were reported only in one review [ 25 ]. Five reviews presented a table summarizing bias, using various risk of bias tools [ 25 , 29 , 39 , 40 , 41 ]. One review analyzed “study quality” [ 37 ]. One review mentioned the risk of bias assessment in the methodology but did not provide any related analysis [ 28 ].

This overview of systematic reviews analyzed the first 18 systematic reviews published after the onset of the COVID-19 pandemic, up to March 24, 2020, with primary studies involving more than 60,000 patients. Using AMSTAR-2, we judged that our confidence in all those reviews was “critically low”. Ten reviews included meta-analyses. The reviews presented data on clinical manifestations, laboratory and radiological findings, and interventions. We found no systematic reviews on the utility of diagnostic tests.

Symptoms were reported in seven reviews; most of the patients had a fever, cough, dyspnea, myalgia or muscle fatigue, and gastrointestinal disorders such as diarrhea, nausea, or vomiting. Olfactory dysfunction (anosmia or dysosmia) has been described in patients infected with COVID-19 [ 43 ]; however, this was not reported in any of the reviews included in this overview. During the SARS outbreak in 2002, there were reports of impairment of the sense of smell associated with the disease [ 44 , 45 ].

The reported mortality rates ranged from 0.3 to 14% in the included reviews. Mortality estimates are influenced by the transmissibility rate (basic reproduction number), availability of diagnostic tools, notification policies, asymptomatic presentations of the disease, resources for disease prevention and control, and treatment facilities; variability in the mortality rate fits the pattern of emerging infectious diseases [ 46 ]. Furthermore, the reported cases did not consider asymptomatic cases, mild cases where individuals have not sought medical treatment, and the fact that many countries had limited access to diagnostic tests or have implemented testing policies later than the others. Considering the lack of reviews assessing diagnostic testing (sensitivity, specificity, and predictive values of RT-PCT or immunoglobulin tests), and the preponderance of studies that assessed only symptomatic individuals, considerable imprecision around the calculated mortality rates existed in the early stage of the COVID-19 pandemic.

Few reviews included treatment data. Those reviews described studies considered to be at a very low level of evidence: usually small, retrospective studies with very heterogeneous populations. Seven reviews analyzed laboratory parameters; those reviews could have been useful for clinicians who attend patients suspected of COVID-19 in emergency services worldwide, such as assessing which patients need to be reassessed more frequently.

All systematic reviews scored poorly on the AMSTAR 2 critical appraisal tool for systematic reviews. Most of the original studies included in the reviews were case series and case reports, impacting the quality of evidence. Such evidence has major implications for clinical practice and the use of these reviews in evidence-based practice and policy. Clinicians, patients, and policymakers can only have the highest confidence in systematic review findings if high-quality systematic review methodologies are employed. The urgent need for information during a pandemic does not justify poor quality reporting.

We acknowledge that there are numerous challenges associated with analyzing COVID-19 data during a pandemic [ 47 ]. High-quality evidence syntheses are needed for decision-making, but each type of evidence syntheses is associated with its inherent challenges.

The creation of classic systematic reviews requires considerable time and effort; with massive research output, they quickly become outdated, and preparing updated versions also requires considerable time. A recent study showed that updates of non-Cochrane systematic reviews are published a median of 5 years after the publication of the previous version [ 48 ].

Authors may register a review and then abandon it [ 49 ], but the existence of a public record that is not updated may lead other authors to believe that the review is still ongoing. A quarter of Cochrane review protocols remains unpublished as completed systematic reviews 8 years after protocol publication [ 50 ].

Rapid reviews can be used to summarize the evidence, but they involve methodological sacrifices and simplifications to produce information promptly, with inconsistent methodological approaches [ 51 ]. However, rapid reviews are justified in times of public health emergencies, and even Cochrane has resorted to publishing rapid reviews in response to the COVID-19 crisis [ 52 ]. Rapid reviews were eligible for inclusion in this overview, but only one of the 18 reviews included in this study was labeled as a rapid review.

Ideally, COVID-19 evidence would be continually summarized in a series of high-quality living systematic reviews, types of evidence synthesis defined as “ a systematic review which is continually updated, incorporating relevant new evidence as it becomes available ” [ 53 ]. However, conducting living systematic reviews requires considerable resources, calling into question the sustainability of such evidence synthesis over long periods [ 54 ].

Research reports about COVID-19 will contribute to research waste if they are poorly designed, poorly reported, or simply not necessary. In principle, systematic reviews should help reduce research waste as they usually provide recommendations for further research that is needed or may advise that sufficient evidence exists on a particular topic [ 55 ]. However, systematic reviews can also contribute to growing research waste when they are not needed, or poorly conducted and reported. Our present study clearly shows that most of the systematic reviews that were published early on in the COVID-19 pandemic could be categorized as research waste, as our confidence in their results is critically low.

Our study has some limitations. One is that for AMSTAR 2 assessment we relied on information available in publications; we did not attempt to contact study authors for clarifications or additional data. In three reviews, the methodological quality appraisal was challenging because they were published as letters, or labeled as rapid communications. As a result, various details about their review process were not included, leading to AMSTAR 2 questions being answered as “not reported”, resulting in low confidence scores. Full manuscripts might have provided additional information that could have led to higher confidence in the results. In other words, low scores could reflect incomplete reporting, not necessarily low-quality review methods. To make their review available more rapidly and more concisely, the authors may have omitted methodological details. A general issue during a crisis is that speed and completeness must be balanced. However, maintaining high standards requires proper resourcing and commitment to ensure that the users of systematic reviews can have high confidence in the results.

Furthermore, we used adjusted AMSTAR 2 scoring, as the tool was designed for critical appraisal of reviews of interventions. Some reviews may have received lower scores than actually warranted in spite of these adjustments.

Another limitation of our study may be the inclusion of multiple overlapping reviews, as some included reviews included the same primary studies. According to the Cochrane Handbook, including overlapping reviews may be appropriate when the review’s aim is “ to present and describe the current body of systematic review evidence on a topic ” [ 12 ], which was our aim. To avoid bias with summarizing evidence from overlapping reviews, we presented the forest plots without summary estimates. The forest plots serve to inform readers about the effect sizes for outcomes that were reported in each review.

Several authors from this study have contributed to one of the reviews identified [ 25 ]. To reduce the risk of any bias, two authors who did not co-author the review in question initially assessed its quality and limitations.

Finally, we note that the systematic reviews included in our overview may have had issues that our analysis did not identify because we did not analyze their primary studies to verify the accuracy of the data and information they presented. We give two examples to substantiate this possibility. Lovato et al. wrote a commentary on the review of Sun et al. [ 41 ], in which they criticized the authors’ conclusion that sore throat is rare in COVID-19 patients [ 56 ]. Lovato et al. highlighted that multiple studies included in Sun et al. did not accurately describe participants’ clinical presentations, warning that only three studies clearly reported data on sore throat [ 56 ].

In another example, Leung [ 57 ] warned about the review of Li, L.Q. et al. [ 29 ]: “ it is possible that this statistic was computed using overlapped samples, therefore some patients were double counted ”. Li et al. responded to Leung that it is uncertain whether the data overlapped, as they used data from published articles and did not have access to the original data; they also reported that they requested original data and that they plan to re-do their analyses once they receive them; they also urged readers to treat the data with caution [ 58 ]. This points to the evolving nature of evidence during a crisis.

Our study’s strength is that this overview adds to the current knowledge by providing a comprehensive summary of all the evidence synthesis about COVID-19 available early after the onset of the pandemic. This overview followed strict methodological criteria, including a comprehensive and sensitive search strategy and a standard tool for methodological appraisal of systematic reviews.

In conclusion, in this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all the reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic could be categorized as research waste. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards to provide patients, clinicians, and decision-makers trustworthy evidence.

Availability of data and materials

All data collected and analyzed within this study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Catherine Henderson DPhil from Swanscoe Communications for pro bono medical writing and editing support. We acknowledge support from the Covidence Team, specifically Anneliese Arno. We thank the whole International Network of Coronavirus Disease 2019 (InterNetCOVID-19) for their commitment and involvement. Members of the InterNetCOVID-19 are listed in Additional file 6 . We thank Pavel Cerny and Roger Crosthwaite for guiding the team supervisor (IJBN) on human resources management.

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Israel Júnior Borges do Nascimento & Milena Soriano Marcolino

Medical College of Wisconsin, Milwaukee, WI, USA

Israel Júnior Borges do Nascimento

Helene Fuld Health Trust National Institute for Evidence-based Practice in Nursing and Healthcare, College of Nursing, The Ohio State University, Columbus, OH, USA

Dónal P. O’Mathúna

School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland

Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany

Thilo Caspar von Groote

Department of Sport and Health Science, Technische Universität München, Munich, Germany

Hebatullah Mohamed Abdulazeem

School of Health Sciences, Faculty of Health and Medicine, The University of Newcastle, Callaghan, Australia

Ishanka Weerasekara

Department of Physiotherapy, Faculty of Allied Health Sciences, University of Peradeniya, Peradeniya, Sri Lanka

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Ana Marusic, Irena Zakarija-Grkovic & Tina Poklepovic Pericic

Center for Evidence-Based Medicine and Health Care, Catholic University of Croatia, Ilica 242, 10000, Zagreb, Croatia

Livia Puljak

Cochrane Brazil, Evidence-Based Health Program, Universidade Federal de São Paulo, São Paulo, Brazil

Vinicius Tassoni Civile & Alvaro Nagib Atallah

Yorkville University, Fredericton, New Brunswick, Canada

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IJBN conceived the research idea and worked as a project coordinator. DPOM, TCVG, HMA, IW, AM, LP, VTC, IZG, TPP, ANA, SF, NLB and MSM were involved in data curation, formal analysis, investigation, methodology, and initial draft writing. All authors revised the manuscript critically for the content. The author(s) read and approved the final manuscript.

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Supplementary Information

Additional file 1: appendix 1..

Search strategies used in the study.

Additional file 2: Appendix 2.

Adjusted scoring of AMSTAR 2 used in this study for systematic reviews of studies that did not analyze interventions.

Additional file 3: Appendix 3.

List of excluded studies, with reasons.

Additional file 4: Appendix 4.

Table of overlapping studies, containing the list of primary studies included, their visual overlap in individual systematic reviews, and the number in how many reviews each primary study was included.

Additional file 5: Appendix 5.

A detailed explanation of AMSTAR scoring for each item in each review.

Additional file 6: Appendix 6.

List of members and affiliates of International Network of Coronavirus Disease 2019 (InterNetCOVID-19).

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Borges do Nascimento, I.J., O’Mathúna, D.P., von Groote, T.C. et al. Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews. BMC Infect Dis 21 , 525 (2021). https://doi.org/10.1186/s12879-021-06214-4

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MINI REVIEW article

Covid-19: emergence, spread, possible treatments, and global burden.

• 1 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
• 2 Department of Health Sciences, School of Education and Health, Cape Breton University, Sydney, NS, Canada

The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.

Introduction

Coronaviridae is a family of viruses with a positive-sense RNA that possess an outer viral coat. When looked at with the help of an electron microscope, there appears to be a unique corona around it. This family of viruses mainly cause respiratory diseases in humans, in the forms of common cold or pneumonia as well as respiratory infections. These viruses can infect animals as well ( 1 , 2 ). Up until the year 2003, coronavirus (CoV) had attracted limited interest from researchers. However, after the SARS (severe acute respiratory syndrome) outbreak caused by the SARS-CoV, the coronavirus was looked at with renewed interest ( 3 , 4 ). This also happened to be the first epidemic of the 21st century originating in the Guangdong province of China. Almost 10 years later, there was a MERS (Middle East respiratory syndrome) outbreak in 2012, which was caused by the MERS-CoV ( 5 , 6 ). Both SARS and MERS have a zoonotic origin and originated from bats. A unique feature of these viruses is the ability to mutate rapidly and adapt to a new host. The zoonotic origin of these viruses allows them to jump from host to host. Coronaviruses are known to use the angiotensin-converting enzyme-2 (ACE-2) receptor or the dipeptidyl peptidase IV (DPP-4) protein to gain entry into cells for replication ( 7 – 10 ).

In December 2019, almost seven years after the MERS 2012 outbreak, a novel Coronavirus (2019-nCoV) surfaced in Wuhan in the Hubei region of China. The outbreak rapidly grew and spread to neighboring countries. However, rapid communication of information and the increasing scale of events led to quick quarantine and screening of travelers, thus containing the spread of the infection. The major part of the infection was restricted to China, and a second cluster was found on a cruise ship called the Diamond Princess docked in Japan ( 11 , 12 ).

The new virus was identified to be a novel Coronavirus and was thus initially named 2019-nCoV; later, it was renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ( 13 ), and the disease it causes is now referred to as Coronavirus Disease-2019 (COVID-19) by the WHO. The virus was suspected to have begun its spread in the Huanan seafood wholesale market in the Wuhan region. It is possible that an animal that was carrying the virus was brought into or sold in the market, causing the spread of the virus in the crowded marketplace. One of the first claims made was in an article published in the Journal of Medical Virology ( 14 ), which identified snakes as the possible host. A second possibility was that pangolins could be the wild host of SARS-CoV-2 ( 15 ), though the most likely possibility is that the virus originated from bats ( 13 , 16 – 19 ). Increasing evidence and experts are now collectively concluding the virus had a natural origin in bats, as with previous such respiratory viruses ( 2 , 20 – 24 ).

Similarly, SARS and MERS were also suspected to originate from bats. In the case of MERS, the dromedary camel is an intermediate host ( 5 , 10 ). Bats have been known to harbor coronaviruses for quite some time now. Just as in the case of avian flu, SARS, MERS, and possibly even HIV, with increasing selection and ecological pressure due to human activities, the virus made the jump from animal to man. Humans have been encroaching increasingly into forests, and this is true over much of China, as in Africa. Combined with additional ecological pressure due to climate change, such zoonotic spillovers are now more common than ever. It is likely that the next disease X will also have such an origin ( 25 ). We have learned the importance of identification of the source organism due to the Ebola virus pandemic. Viruses are unstable organisms genetically, constantly mutating by genetic shift or drift. It is not possible to predict when a cross-species jump may occur and when a seemingly harmless variant form of the virus may turn into a deadly strain. Such an incident occurred in Reston, USA, with the Reston virus ( 26 ), an alarming reminder of this possibility. The identification of the original host helps us to contain future spreads as well as to learn about the mechanism of transmission of viruses. Until the virus is isolated from a wild animal host, in this case, mostly bats, the zoonotic origin will remain hypothetical, though likely. It should further be noted that the virus has acquired several mutations, as noted by a group in China, indicating that there are more than two strains of the virus, which may have had an impact on its pathogenicity. However, this claim remains unproven, and many experts have argued otherwise; data proving this are not yet available ( 27 ). A similar finding was reported from Italy and India independently, where they found two strains ( 28 , 29 ). These findings need to be further cross-verified by similar analyses globally. If true, this finding could effectively explain why some nations are more affected than others.

Transmission

When the spread of COVID-19 began ( Figure 1 ), the virus appeared to be contained within China and the cruise ship “Diamond Princess,” which formed the major clusters of the virus. However, as of April 2020, over 210 countries and territories are affected by the virus, with Europe, the USA, and Iran forming the new cluster of the virus. The USA ( Figure 2 ) has the highest number of confirmed COVID-19 cases, whereas India and China, despite being among the most population-dense countries in the world, have managed to constrain the infection rate by the implementation of a complete lockdown with arrangements in place to manage the confirmed cases. Similarly, the UK has also managed to maintain a low curve of the graph by implementing similar measures, though it was not strictly enforced. Reports have indicated that the presence of different strains or strands of the virus may have had an effect on the management of the infection rate of the virus ( 27 – 29 ). The disease is spread by droplet transmission. As of April 2020, the total number of infected individuals stands at around 3 million, with ~200,000 deaths and more than 1 million recoveries globally ( 30 , 34 ). The virus thus has a fatality rate of around 2% and an R 0 of 3 based on current data. However, a more recent report from the CDC, Atlanta, USA, claims that the R 0 could be as high as 5.7 ( 35 ). It has also been observed from data available from China and India that individuals likely to be infected by the virus from both these countries belong to the age groups of 20–50 years ( 36 , 37 ). In both of these countries, the working class mostly belongs to this age group, making exposure more likely. Germany and Singapore are great examples of countries with a high number of cases but low fatalities as compared to their immediate neighbors. Singapore is one of the few countries that had developed a detailed plan of action after the previous SARS outbreak to deal with a similar situation in the future, and this worked in their favor during this outbreak. Both countries took swift action after the outbreak began, with Singapore banning Chinese travelers and implementing screening and quarantine measures at a time when the WHO recommended none. They ordered the elderly and the vulnerable to strictly stay at home, and they ensured that lifesaving equipment and large-scale testing facilities were available immediately ( 38 , 39 ). Germany took similar measures by ramping up testing capacity quite early and by ensuring that all individuals had equal opportunity to get tested. This meant that young, old, and at-risk people all got tested, thus ensuring positive results early during disease progression and that most cases were mild like in Singapore, thus maintaining a lower death percentage ( 40 ). It allowed infected individuals to be identified and quarantined before they even had symptoms. Testing was carried out at multiple labs, reducing the load and providing massive scale, something which countries such as the USA did quite late and India restricted to select government and private labs. The German government also banned large gatherings and advocated social distancing to further reduce the spread, though unlike India and the USA, this was done quite late. South Korea is another example of how a nation has managed to contain the spread and transmission of the infection. South Korea and the USA both reported their first COVID-19 cases on the same day; however, the US administration downplayed the risks of the disease, unlike South Korean officials, who constantly informed their citizens about the developments of the disease using the media and a centralized messaging system. They also employed the Trace, Test, and Treat protocol to identify and isolate patients fast, whereas the USA restricted this to patients with severe infection and only later broadened this criterion, like many European countries as well as India. Unlike the USA, South Korea also has universal healthcare, ensuring free diagnostic testing.

Figure 1 . Timeline of COVID-19 progression ( 30 – 32 ).

Figure 2 . Total confirmed COVID 19 cases as of May 2020 ( 33 ).

The main mode of transmission of 2019-nCoV is human to human. As of now, animal-to-human transfer has not yet been confirmed. Asymptomatic carriers of the virus are at major risk of being superinfectors with this disease, as all those infected may not develop the disease ( 41 ). This is a concern that has been raised by nations globally, with the Indian government raising concerns on how to identify and contain asymptomatic carriers, who could account for 80% of those infected ( 42 ). Since current resources are directed towards understanding the hospitalized individuals showing symptoms, there is still a vast amount of information about asymptomatic individuals that has yet to be studied. For example, some questions that need to be answered include: Do asymptomatic individuals develop the disease at any point in time at all? Do they eventually develop antibodies? How long do they shed the virus for? Can any tissue of these individuals store the virus in a dormant state? Asymptomatic transmission is a gray area that encompasses major unknowns in COVID-19.

The main route of human-to-human transmission is by droplets, which are generated during coughing, talking, or sneezing and are then inhaled by a healthy individual. They can also be indirectly transmitted to a person when they land on surfaces that are touched by a healthy individual who may then touch their nose, mouth, or eyes, allowing the virus entry into the body. Fomites are also a common issue in such diseases ( 43 ).

Aerosol-based transmission of the virus has not yet been confirmed ( 43 ). Stool-based transmission via the fecal-oral route may also be possible since the SARS-CoV-2 has been found in patient feces ( 44 , 45 ). Some patients with COVID-19 tend to develop diarrhea, which can become a major route of transmission if proper sanitation and personal hygiene needs are not met. There is no evidence currently available to suggest intrauterine vertical transmission of the disease in pregnant women ( 46 ).

More investigation is necessary of whether climate has played any role in the containment of the infection in countries such as India, Singapore, China, and Israel, as these are significantly warmer countries as compared with the UK, the USA, and Canada ( Figure 2 ). Ideally, a warm climate should prevent the virus from surviving for longer periods of time on surfaces, reducing transmissibility.

Pathophysiology

On gaining entry via any of the mucus membranes, the single-stranded RNA-based virus enters the host cell using type 2 transmembrane serine protease (TMPRSS2) and ACE2 receptor protein, leading to fusion and endocytosis with the host cell ( 47 – 49 ). The uncoated RNA is then translated, and viral proteins are synthesized. With the help of RNA-dependant RNA polymerase, new RNA is produced for the new virions. The cell then undergoes lysis, releasing a load of new virions into the patients' body. The resultant infection causes a massive release of pro-inflammatory cytokines that causes a cytokine storm.

Clinical Presentation

The clinical presentation of the disease resembles beta coronavirus infections. The virus has an incubation time of 2–14 days, which is the reason why most patients suspected to have the illness or contact with an individual having the illness remain in quarantine for the said amount of time. Infection with SARS-CoV-2 causes severe pneumonia, intermittent fever, and cough ( 50 , 51 ). Symptoms of rhinorrhoea, pharyngitis, and sneezing have been less commonly seen. Patients often develop acute respiratory distress syndrome within 2 days of hospital admission, requiring ventilatory support. It has been observed that during this phase, the mortality tends to be high. Chest CT will show indicators of pneumonia and ground-glass opacity, a feature that has helped to improve the preliminary diagnosis ( 51 ). The primary method of diagnosis for SARS-CoV-2 is with the help of PCR. For the PCR testing, the US CDC recommends testing for the N gene, whereas the Chinese CDC recommends the use of ORF lab and N gene of the viral genome for testing. Some also rely on the radiological findings for preliminary screening ( 52 ). Additionally, immunodiagnostic tests based on the presence of antibodies can also play a role in testing. While the WHO recommends the use of these tests for research use, many countries have pre-emptively deployed the use of these tests in the hope of ramping up the rate and speed of testing ( 52 – 54 ). Later, they noticed variations among the results, causing them to stop the use of such kits; there was also debate among the experts about the sensitivity and specificity of the tests. For immunological tests, it is beneficial to test for antibodies against the virus produced by the body rather than to test for the presence of the viral proteins, since the antibodies can be present in larger titers for a longer span of time. However, the cross-reactivity of these tests with other coronavirus antibodies is something that needs verification. Biochemical parameters such as D-dimer, C-reactive protein, and variations in neutrophil and lymphocyte counts are some other parameters that can be used to make a preliminary diagnosis; however, these parameters vary in a number of diseases and thus cannot be relied upon conclusively ( 51 ). Patients with pre-existing diseases such as asthma or similar lung disorder are at higher risk, requiring life support, as are those with other diseases such as diabetes, hypertension, or obesity. Those above the age of 60 have displayed the highest mortality rate in China, a finding that is mirrored in other nations as well ( Figure 3 ) ( 55 ). If we cross-verify these findings with the population share that is above the age of 70, we find that Italy, the United Kingdom, Canada, and the USA have one of the highest elderly populations as compared to countries such as India and China ( Figure 4 ), and this also reflects the case fatality rates accordingly ( Figure 5 ) ( 33 ). This is a clear indicator that aside from comorbidities, age is also an independent risk factor for death in those infected by COVID-19. Also, in the US, it was seen that the rates of African American deaths were higher. This is probably due to the fact that the prevalence of hypertension and obesity in this community is higher than in Caucasians ( 56 , 57 ). In late April 2020, there are also claims in the US media that young patients in the US with COVID-19 may be at increased risk of stroke; however, this is yet to be proven. We know that coagulopathy is a feature of COVID-19, and thus stroke is likely in this condition ( 58 , 59 ). The main cause of death in COVID-19 patients was acute respiratory distress due to the inflammation in the linings of the lungs caused by the cytokine storm, which is seen in all non-survival cases and in respiratory failure. The resultant inflammation in the lungs, served as an entry point of further infection, associated with coagulopathy end-organ failure, septic shock, and secondary infections leading to death ( 60 – 63 ).

Figure 3 . Case fatality rate by age in selected countries as of April 2020 ( 33 ).

Figure 4 . Case fatality rate in selected countries ( 33 ).

Figure 5 . Population share above 70 years of age ( 33 ).

For COVID-19, there is no specific treatment available. The WHO announced the organization of a trial dubbed the “Solidarity” clinical trial for COVID-19 treatments ( 64 ). This is an international collaborative study that investigates the use of a few prime candidate drugs for use against COVID-19, which are discussed below. The study is designed to reduce the time taken for an RCT by over 80%. There are over 1087 studies ( Supplementary Data 1 ) for COVID-19 registered at clinicaltrials.gov , of which 657 are interventional studies ( Supplementary Data 2 ) ( 65 ). The primary focus of the interventional studies for COVID-19 has been on antimalarial drugs and antiviral agents ( Table 1 ), while over 200 studies deal with the use of different forms of oxygen therapy. Most trials focus on improvement of clinical status, reduction of viral load, time to improvement, and reduction of mortality rates. These studies cover both severe and mild cases.

Table 1 . List of therapeutic drugs under study for COVID-19 as per clinical trials registered under clinicaltrials.gov .

Use of Antimalarial Drugs Against SARS-CoV-2

The use of chloroquine for the treatment of corona virus-based infection has shown some benefit in the prevention of viral replication in the cases of SARS and MERS. However, it was not validated on a large scale in the form of a randomized control trial ( 50 , 66 – 68 ). The drugs of choice among antimalarials are Chloroquine (CQ) and Hydroxychloroquine (HCQ). The use of CQ for COVID-19 was brought to light by the Chinese, especially by the publication of a letter to the editor of Bioscience Trends by Gao et al. ( 69 ). The letter claimed that several studies found CQ to be effective against COVID-19; however, the letter did not provide many details. Immediately, over a short span of time, interest in these two agents grew globally. Early in vitro data have revealed that chloroquine can inhibit the viral replication ( 70 , 71 ).

HCQ and CQ work by raising the pH of the lysosome, the cellular organelle that is responsible for phagocytic degradation. Its function is to combine with cell contents that have been phagocytosed and break them down eventually, in some immune cells, as a downstream process to display some of the broken proteins as antigens, thus further enhancing the immune recruitment against an antigen/pathogen. The drug was to be administered alone or with azithromycin. The use of azithromycin may be advocated by the fact that it has been seen previously to have some immunomodulatory role in airway-related disease. It appears to reduce the release of pro-inflammatory cytokines in respiratory illnesses ( 72 ). However, HCQ and azithromycin are known to have a major drug interaction when co-administered, which increases the risk of QT interval prolongation ( 73 ). Quinine-based drugs are known to have adverse effects such as QT prolongation, retinal damage, hypoglycemia, and hemolysis of blood in patients with G-6-PD deficiency ( 66 ). Several preprints, including, a metanalysis now indicate that HCQ may have no benefit for severe or critically ill patients who have COVID-19 where the outcome is need for ventilation or death ( 74 , 75 ). As of April 21, 2020, after having pre-emptively recommended their use for SARS-CoV-2 infection, the US now advocates against the use of these two drugs based on the new data that has become available.

Use of Antiviral Drugs Against SARS-CoV-2

The antiviral agents are mainly those used in the case of HIV/AIDS, these being Lopinavir and Ritonavir. Other agents such as nucleoside analogs like Favipiravir, Ribavirin, Remdesivir, and Galidesivir have been tested for possible activity in the prevention of viral RNA synthesis ( 76 ). Among these drugs, Lopinavir, Ritonavir, and Remdesivir are listed in the Solidarity trial by the WHO.

Remdesivir is a nucleotide analog for adenosine that gets incorporated into the viral RNA, hindering its replication and causing chain termination. This agent was originally developed for Ebola Virus Disease ( 77 ). A study was conducted with rhesus macaques infected with SARS-CoV-2 ( 78 ). In that study, after 12 h of infection, the monkeys were treated with either Remdesivir or vehicle. The drug showed good distribution in the lungs, and the animals treated with the drug showed a better clinical score than the vehicle group. The radiological findings of the study also indicated that the animals treated with Remdesivir have less lung damage. There was a reduction in viral replication but not in virus shedding. Furthermore, there were no mutations found in the RNA polymerase sequences. A randomized clinical control study that became available in late April 2020 ( 79 ), having 158 on the Remdesivir arm and 79 on the placebo arm, found that Remdesivir reduced the time to recovery in the Remdesivir-treated arm to 11 days, while the placebo-arm recovery time was 15 days. Though this was not found to be statistically significant, the agent provided a basis for further studies. The 28-days mortality was found to be similar for both groups. This has now provided us with a basis on which to develop future molecules. The study has been supported by the National Institute of Health, USA. The authors of the study advocated for more clinical trials with Remdesivir with a larger population. Such larger studies are already in progress, and their results are awaited. Remdesivir is currently one of the drugs that hold most promise against COVID-19.

An early trial in China with Lopinavir and Ritonavir showed no benefit compared with standard clinical care ( 80 ). More studies with this drug are currently underway, including one in India ( 81 , 82 ).

Use of Convalescent Patient Plasma

Another possible option would be the use of serum from convalescent individuals, as this is known to contain antibodies that can neutralize the virus and aid in its elimination. This has been tried previously for other coronavirus infections ( 83 ). Early emerging case reports in this aspect look promising compared to other therapies that have been tried ( 84 – 87 ). A report from China indicates that five patients treated with plasma recovered and were eventually weaned off ventilators ( 84 ). They exhibited reductions in fever and viral load and improved oxygenation. The virus was not detected in the patients after 12 days of plasma transfusion. The US FDA has provided detailed recommendations for investigational COVID-19 Convalescent Plasma use ( 88 ). One of the benefits of this approach is that it can also be used for post-exposure prophylaxis. This approach is now beginning to be increasingly adopted in other countries, with over 95 trials registered on clinicaltrials.gov alone, of which at least 75 are interventional ( 89 ). The use of convalescent patient plasma, though mostly for research purposes, appears to be the best and, so far, the only successful option for treatment available.

From a future perspective, the use of monoclonal antibodies for the inhibition of the attachment of the virus to the ACE-2 receptor may be the best bet. Aside from this, ACE-2-like molecules could also be utilized to attach and inactivate the viral proteins, since inhibition of the ACE-2 receptor would not be advisable due to its negative repercussions physiologically. In the absence of drug regimens and a vaccine, the treatment is symptomatic and involves the use of non-invasive ventilation or intubation where necessary for respiratory failure patients. Patients that may go into septic shock should be managed as per existing guidelines with hemodynamic support as well as antibiotics where necessary.

The WHO has recommended that simple personal hygiene practices can be sufficient for the prevention of spread and containment of the disease ( 90 ). Practices such as frequent washing of soiled hands or the use of sanitizer for unsoiled hands help reduce transmission. Covering of mouth while sneezing and coughing, and disinfection of surfaces that are frequently touched, such as tabletops, doorknobs, and switches with 70% isopropyl alcohol or other disinfectants are broadly recommended. It is recommended that all individuals afflicted by the disease, as well as those caring for the infected, wear a mask to avoid transmission. Healthcare works are advised to wear a complete set of personal protective equipment as per WHO-provided guidelines. Fumigation of dormitories, quarantine rooms, and washing of clothes and other fomites with detergent and warm water can help get rid of the virus. Parcels and goods are not known to transmit the virus, as per information provided by the WHO, since the virus is not able to survive sufficiently in an open, exposed environment. Quarantine of infected individuals and those who have come into contact with an infected individual is necessary to further prevent transmission of the virus ( 91 ). Quarantine is an age-old archaic practice that continues to hold relevance even today for disease containment. With the quarantine being implemented on such a large scale in some countries, taking the form of a national lockdown, the question arises of its impact on the mental health of all individuals. This topic needs to be addressed, especially in countries such as India and China, where it is still a matter of partial taboo to talk about it openly within the society.

In India, the Ministry of Ayurveda, Yoga, and Naturopathy, Unani, Siddha and Homeopathy (AYUSH), which deals with the alternative forms of medicine, issued a press release that the homeopathic, drug Arsenicum album 30, can be taken on an empty stomach for 3 days to provide protection against the infection ( 92 ). It also provided a list of herbal drugs in the same press release as per Ayurvedic and Unani systems of medicine that can boost the immune system to deal with the virus. However, there is currently no evidence to support the use of these systems of medicine against COVID-19, and they need to be tested.

The prevention of the disease with the use of a vaccine would provide a more viable solution. There are no vaccines available for any of the coronaviruses, which includes SARS and MERS. The development of a vaccine, however, is in progress at a rapid pace, though it could take about a year or two. As of April 2020, no vaccine has completed the development and testing process. A popular approach has been with the use of mRNA-based vaccine ( 93 – 96 ). mRNA vaccines have the advantage over conventional vaccines in terms of production, since they can be manufactured easily and do not have to be cultured, as a virus would need to be. Alternative conventional approaches to making a vaccine against SARS-CoV-2 would include the use of live attenuated virus as well as using the isolated spike proteins of the virus. Both of these approaches are in progress for vaccine development ( 97 ). Governments across the world have poured in resources and made changes in their legislation to ensure rapid development, testing, and deployment of a vaccine.

Barriers to Treatment

Lack of transparency and poor media relations.

The lack of government transparency and poor reporting by the media have hampered the measures that could have been taken by healthcare systems globally to deal with the COVID-19 threat. The CDC, as well as the US administration, downplayed the threat and thus failed to stock up on essential supplies, ventilators, and test kits. An early warning system, if implemented, would have caused borders to be shut and early lockdowns. The WHO also delayed its response in sounding the alarm regarding the severity of the outbreak to allow nations globally to prepare for a pandemic. Singapore is a prime example where, despite the WHO not raising concerns and banning travel to and from China, a country banned travelers and took early measures, thus managing the outbreak quite well. South Korea is another example of how things may have played out had those measures by agencies been taken with transparency. Increased transparency would have allowed the healthcare sector to better prepare and reduced the load of patients they had to deal with, helping flatten the curve. The increased patient load and confusion among citizens arising from not following these practices has proved to be a barrier to providing effective treatments to patients with the disease elsewhere in the world.

Lack of Preparedness and Protocols

Despite the previous SARS outbreak teaching us important lessons and providing us with data on a potential outbreak, many nations did not take the important measures needed for a future outbreak. There was no allocation of sufficient funds for such an event. Many countries experienced severe lack of PPE, and the lockdown precautions hampered the logistics of supply and manufacturing of such essential equipment. Singapore and South Korea had protocols in place and were able to implement them at a moment's notice. The spurt of cases that Korea experienced was managed well, providing evidence to this effect. The lack of preparedness and lack of protocol in other nations has resulted in confusion as to how the treatment may be administered safely to the large volume of patients while dealing with diagnostics. Both of these factors have limited the accessibility to healthcare services due to sheer volume.

Socio-Economic Impact

During the SARS epidemic, China faced an economic setback, and experts were unsure if any recovery would be made. However, the global and domestic situation was then in China's favor, as it had a lower debt, allowing it to make a speedy recovery. This is not the case now. Global experts have a pessimistic outlook on the outcome of this outbreak ( 98 ). The fear of COVID-19 disease, lack of proper understanding of the dangers of the virus, and the misinformation spread on the social media ( 99 ) have caused a breakdown of the economic flow globally ( 100 ). An example of this is Indonesia, where a great amount of fear was expressed in responses to a survey when the nation was still free of COVID-19 ( 101 ). The pandemic has resulted in over 2.6 billion people being put under lockdown. This lockdown and the cancellation of the lunar year celebration has affected business at the local level. Hundreds of flights have been canceled, and tourism globally has been affected. Japan and Indonesia are estimated to lose over 2.44 billion dollars due to this ( 102 , 103 ). Workers are not able to work in factories, transportation in all forms is restricted, and goods are not produced or moved. The transport of finished products and raw materials out of China is low. The Economist has published US stock market details indicating that companies in the US that have Chinese roots fell, on average, 5 points on the stock market as compared to the S&P 500 index ( 104 ). Companies such as Starbucks have had to close over 4,000 outlets due to the outbreak as a precaution. Tech and pharma companies are at higher risk since they rely on China for the supply of raw materials and active pharmaceutical ingredients. Paracetamol, for one, has reported a price increase of over 40% in India ( 104 – 106 ). Mass hysteria in the market has caused selling of shares of these companies, causing a tumble in the Indian stock market. Though long-term investors will not be significantly affected, short-term traders will find themselves in soup. Politically, however, this has further bolstered support for world leaders in countries such as India, Germany, and the UK, who are achieving good approval ratings, with citizens being satisfied with the government's approach. In contrast, the ratings of US President Donald Trump have dropped due to the manner in which the COVID-19 pandemic was handled. These minor impacts may be of temporary significance, and the worst and direct impact will be on China itself ( 107 – 109 ), as the looming trade war with the USA had a negative impact on the Chinese and Asian markets. The longer production of goods continues to remain suspended, the more adversely it will affect the Chinese economy and the global markets dependent on it ( 110 ). If this disease is not contained, more and more lockdowns by multiple nations will severely affect the economy and lead to many social complications.

The appearance of the 2019 Novel Coronavirus has added and will continue to add to our understanding of viruses. The pandemic has once again tested the world's preparedness for dealing with such outbreaks. It has provided an outlook on how a massive-scale biological event can cause a socio-economic disturbance through misinformation and social media. In the coming months and years, we can expect to gain further insights into SARS-CoV-2 and COVID-19.

Author Contributions

KN: conceptualization. RK, AA, JM, and KN: investigation. RK and AA: writing—original draft preparation. KN, PN, and JM: writing—review and editing. KN: supervision.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

The authors would like to acknowledge the contributions made by Dr. Piya Paul Mudgal, Assistant Professor, Manipal Institute of Virology, Manipal Academy of Higher Education towards inputs provided by her during the drafting of the manuscript.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2020.00216/full#supplementary-material

Supplementary Data 1, 2. List of all studies registered for COVID-19 on clinicaltrials.gov .

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Keywords: 2019-nCoV, COVID-19, SARS-CoV-2, coronavirus, pandemic, SARS

Citation: Keni R, Alexander A, Nayak PG, Mudgal J and Nandakumar K (2020) COVID-19: Emergence, Spread, Possible Treatments, and Global Burden. Front. Public Health 8:216. doi: 10.3389/fpubh.2020.00216

Received: 21 February 2020; Accepted: 11 May 2020; Published: 28 May 2020.

Reviewed by:

Copyright © 2020 Keni, Alexander, Nayak, Mudgal and Nandakumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Krishnadas Nandakumar, mailnandakumar77@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Read these 12 moving essays about life during coronavirus

Artists, novelists, critics, and essayists are writing the first draft of history.

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The world is grappling with an invisible, deadly enemy, trying to understand how to live with the threat posed by a virus . For some writers, the only way forward is to put pen to paper, trying to conceptualize and document what it feels like to continue living as countries are under lockdown and regular life seems to have ground to a halt.

So as the coronavirus pandemic has stretched around the world, it’s sparked a crop of diary entries and essays that describe how life has changed. Novelists, critics, artists, and journalists have put words to the feelings many are experiencing. The result is a first draft of how we’ll someday remember this time, filled with uncertainty and pain and fear as well as small moments of hope and humanity.

At the New York Review of Books, Ali Bhutto writes that in Karachi, Pakistan, the government-imposed curfew due to the virus is “eerily reminiscent of past military clampdowns”:

Beneath the quiet calm lies a sense that society has been unhinged and that the usual rules no longer apply. Small groups of pedestrians look on from the shadows, like an audience watching a spectacle slowly unfolding. People pause on street corners and in the shade of trees, under the watchful gaze of the paramilitary forces and the police.

His essay concludes with the sobering note that “in the minds of many, Covid-19 is just another life-threatening hazard in a city that stumbles from one crisis to another.”

Writing from Chattanooga, novelist Jamie Quatro documents the mixed ways her neighbors have been responding to the threat, and the frustration of conflicting direction, or no direction at all, from local, state, and federal leaders:

Whiplash, trying to keep up with who’s ordering what. We’re already experiencing enough chaos without this back-and-forth. Why didn’t the federal government issue a nationwide shelter-in-place at the get-go, the way other countries did? What happens when one state’s shelter-in-place ends, while others continue? Do states still under quarantine close their borders? We are still one nation, not fifty individual countries. Right?

Award-winning photojournalist Alessio Mamo, quarantined with his partner Marta in Sicily after she tested positive for the virus, accompanies his photographs in the Guardian of their confinement with a reflection on being confined :

The doctors asked me to take a second test, but again I tested negative. Perhaps I’m immune? The days dragged on in my apartment, in black and white, like my photos. Sometimes we tried to smile, imagining that I was asymptomatic, because I was the virus. Our smiles seemed to bring good news. My mother left hospital, but I won’t be able to see her for weeks. Marta started breathing well again, and so did I. I would have liked to photograph my country in the midst of this emergency, the battles that the doctors wage on the frontline, the hospitals pushed to their limits, Italy on its knees fighting an invisible enemy. That enemy, a day in March, knocked on my door instead.

In the New York Times Magazine, deputy editor Jessica Lustig writes with devastating clarity about her family’s life in Brooklyn while her husband battled the virus, weeks before most people began taking the threat seriously:

At the door of the clinic, we stand looking out at two older women chatting outside the doorway, oblivious. Do I wave them away? Call out that they should get far away, go home, wash their hands, stay inside? Instead we just stand there, awkwardly, until they move on. Only then do we step outside to begin the long three-block walk home. I point out the early magnolia, the forsythia. T says he is cold. The untrimmed hairs on his neck, under his beard, are white. The few people walking past us on the sidewalk don’t know that we are visitors from the future. A vision, a premonition, a walking visitation. This will be them: Either T, in the mask, or — if they’re lucky — me, tending to him.

Essayist Leslie Jamison writes in the New York Review of Books about being shut away alone in her New York City apartment with her 2-year-old daughter since she became sick:

The virus. Its sinewy, intimate name. What does it feel like in my body today? Shivering under blankets. A hot itch behind the eyes. Three sweatshirts in the middle of the day. My daughter trying to pull another blanket over my body with her tiny arms. An ache in the muscles that somehow makes it hard to lie still. This loss of taste has become a kind of sensory quarantine. It’s as if the quarantine keeps inching closer and closer to my insides. First I lost the touch of other bodies; then I lost the air; now I’ve lost the taste of bananas. Nothing about any of these losses is particularly unique. I’ve made a schedule so I won’t go insane with the toddler. Five days ago, I wrote Walk/Adventure! on it, next to a cut-out illustration of a tiger—as if we’d see tigers on our walks. It was good to keep possibility alive.

At Literary Hub, novelist Heidi Pitlor writes about the elastic nature of time during her family’s quarantine in Massachusetts:

During a shutdown, the things that mark our days—commuting to work, sending our kids to school, having a drink with friends—vanish and time takes on a flat, seamless quality. Without some self-imposed structure, it’s easy to feel a little untethered. A friend recently posted on Facebook: “For those who have lost track, today is Blursday the fortyteenth of Maprilay.” ... Giving shape to time is especially important now, when the future is so shapeless. We do not know whether the virus will continue to rage for weeks or months or, lord help us, on and off for years. We do not know when we will feel safe again. And so many of us, minus those who are gifted at compartmentalization or denial, remain largely captive to fear. We may stay this way if we do not create at least the illusion of movement in our lives, our long days spent with ourselves or partners or families.

Novelist Lauren Groff writes at the New York Review of Books about trying to escape the prison of her fears while sequestered at home in Gainesville, Florida:

Some people have imaginations sparked only by what they can see; I blame this blinkered empiricism for the parks overwhelmed with people, the bars, until a few nights ago, thickly thronged. My imagination is the opposite. I fear everything invisible to me. From the enclosure of my house, I am afraid of the suffering that isn’t present before me, the people running out of money and food or drowning in the fluid in their lungs, the deaths of health-care workers now growing ill while performing their duties. I fear the federal government, which the right wing has so—intentionally—weakened that not only is it insufficient to help its people, it is actively standing in help’s way. I fear we won’t sufficiently punish the right. I fear leaving the house and spreading the disease. I fear what this time of fear is doing to my children, their imaginations, and their souls.

At ArtForum , Berlin-based critic and writer Kristian Vistrup Madsen reflects on martinis, melancholia, and Finnish artist Jaakko Pallasvuo’s 2018 graphic novel Retreat , in which three young people exile themselves in the woods:

In melancholia, the shape of what is ending, and its temporality, is sprawling and incomprehensible. The ambivalence makes it hard to bear. The world of Retreat is rendered in lush pink and purple watercolors, which dissolve into wild and messy abstractions. In apocalypse, the divisions established in genesis bleed back out. My own Corona-retreat is similarly soft, color-field like, each day a blurred succession of quarantinis, YouTube–yoga, and televized press conferences. As restrictions mount, so does abstraction. For now, I’m still rooting for love to save the world.

At the Paris Review , Matt Levin writes about reading Virginia Woolf’s novel The Waves during quarantine:

A retreat, a quarantine, a sickness—they simultaneously distort and clarify, curtail and expand. It is an ideal state in which to read literature with a reputation for difficulty and inaccessibility, those hermetic books shorn of the handholds of conventional plot or characterization or description. A novel like Virginia Woolf’s The Waves is perfect for the state of interiority induced by quarantine—a story of three men and three women, meeting after the death of a mutual friend, told entirely in the overlapping internal monologues of the six, interspersed only with sections of pure, achingly beautiful descriptions of the natural world, a day’s procession and recession of light and waves. The novel is, in my mind’s eye, a perfectly spherical object. It is translucent and shimmering and infinitely fragile, prone to shatter at the slightest disturbance. It is not a book that can be read in snatches on the subway—it demands total absorption. Though it revels in a stark emotional nakedness, the book remains aloof, remote in its own deep self-absorption.

In an essay for the Financial Times, novelist Arundhati Roy writes with anger about Indian Prime Minister Narendra Modi’s anemic response to the threat, but also offers a glimmer of hope for the future:

Historically, pandemics have forced humans to break with the past and imagine their world anew. This one is no different. It is a portal, a gateway between one world and the next. We can choose to walk through it, dragging the carcasses of our prejudice and hatred, our avarice, our data banks and dead ideas, our dead rivers and smoky skies behind us. Or we can walk through lightly, with little luggage, ready to imagine another world. And ready to fight for it.

From Boston, Nora Caplan-Bricker writes in The Point about the strange contraction of space under quarantine, in which a friend in Beirut is as close as the one around the corner in the same city:

It’s a nice illusion—nice to feel like we’re in it together, even if my real world has shrunk to one person, my husband, who sits with his laptop in the other room. It’s nice in the same way as reading those essays that reframe social distancing as solidarity. “We must begin to see the negative space as clearly as the positive, to know what we don’t do is also brilliant and full of love,” the poet Anne Boyer wrote on March 10th, the day that Massachusetts declared a state of emergency. If you squint, you could almost make sense of this quarantine as an effort to flatten, along with the curve, the distinctions we make between our bonds with others. Right now, I care for my neighbor in the same way I demonstrate love for my mother: in all instances, I stay away. And in moments this month, I have loved strangers with an intensity that is new to me. On March 14th, the Saturday night after the end of life as we knew it, I went out with my dog and found the street silent: no lines for restaurants, no children on bicycles, no couples strolling with little cups of ice cream. It had taken the combined will of thousands of people to deliver such a sudden and complete emptiness. I felt so grateful, and so bereft.

And on his own website, musician and artist David Byrne writes about rediscovering the value of working for collective good , saying that “what is happening now is an opportunity to learn how to change our behavior”:

In emergencies, citizens can suddenly cooperate and collaborate. Change can happen. We’re going to need to work together as the effects of climate change ramp up. In order for capitalism to survive in any form, we will have to be a little more socialist. Here is an opportunity for us to see things differently — to see that we really are all connected — and adjust our behavior accordingly. Are we willing to do this? Is this moment an opportunity to see how truly interdependent we all are? To live in a world that is different and better than the one we live in now? We might be too far down the road to test every asymptomatic person, but a change in our mindsets, in how we view our neighbors, could lay the groundwork for the collective action we’ll need to deal with other global crises. The time to see how connected we all are is now.

The portrait these writers paint of a world under quarantine is multifaceted. Our worlds have contracted to the confines of our homes, and yet in some ways we’re more connected than ever to one another. We feel fear and boredom, anger and gratitude, frustration and strange peace. Uncertainty drives us to find metaphors and images that will let us wrap our minds around what is happening.

Yet there’s no single “what” that is happening. Everyone is contending with the pandemic and its effects from different places and in different ways. Reading others’ experiences — even the most frightening ones — can help alleviate the loneliness and dread, a little, and remind us that what we’re going through is both unique and shared by all.

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Collection  29 March 2022

2021 Top 25 COVID-19 Articles

The 25 most downloaded  Nature Communications  articles* on COVID-19 published in 2021 illustrate the collaborative efforts of the international community to combat the ongoing pandemic. These papers highlight valuable research into the biology of coronavirus infection, its detection, treatment as well as into vaccine development and the epidemiology of the disease.

Browse all Top 25 subject area collections  here .

*Data obtained from SN Insights (based on Digital Science's Dimensions) and normalised to account for articles published later in the year.

Research highlights

Anti-spike antibody response to natural SARS-CoV-2 infection in the general population

Most people who are infected with SARS-CoV-2 seroconvert within a few weeks, but the determinants and duration of the antibody response are not known. Here, the authors characterise these features of the immune response using data from a large representative community sample of the UK population.

• Philippa C. Matthews
• the COVID-19 Infection Survey team

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.

• Cathrine Axfors
• Andreas M. Schmitt
• Lars G. Hemkens

Malignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia

Vaccination is an effective strategy in suppressing COVID-19 pandemic, but rare adverse effects have been reported, including cerebral venous thrombosis. Here the authors report two cases of middle cerebral artery infarct within 9-10 days following ChAdOx1 nCov-19 vaccination that also manifest pulmonary and portal vein thrombosis.

• M. De Michele
• M. Iacobucci

Correlation of SARS-CoV-2-breakthrough infections to time-from-vaccine

The duration of effectiveness of SARS-CoV-2 vaccination is not yet known. Here, the authors present preliminary evidence of BNT162b2 vaccine waning across all age groups above 16, with a higher incidence of infection in people who received their second dose early in 2021 compared to later in the year.

• Barak Mizrahi
• Tal Patalon

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al . show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.

• Pinja Jalkanen
• Pekka Kolehmainen
• Ilkka Julkunen

Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection

T cells compose a critical component of the immune response to coronavirus infection with SARS-CoV-2. Here the authors characterise the T cell response to SARS CoV-2 in patients and their close contacts, and show the presence of SARS-CoV-2 specific T cells in the absence of detectable virus infection.

• Zhongfang Wang
• Xiaoyun Yang

Rapid decline of neutralizing antibodies against SARS-CoV-2 among infected healthcare workers

The humoral immune response to SARS-CoV-2 infection is not yet fully understood. Here, Marot et al. monitor the longitudinal profile and neutralizing activity of IgG, IgA, and IgM among 26 healthcare workers and provide evidence for a short-lasting humoral immune protection due to a decrease of neutralizing antibody titers within 3 months.

• Stéphane Marot
• Isabelle Malet
• Anne-Geneviève Marcelin

Efficacy and tolerability of bevacizumab in patients with severe Covid-19

In this single-arm clinical trial, the authors show that treatment of COVID-19 patients with bevacizumab, an anti-vascular endothelial growth factor drug, can improve PaO 2 /FiO 2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.

• Jiaojiao Pang

Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia

A bat origin for SARS-CoV-2 has been proposed. Here, by sampling wild Rhinolophus acuminatus bats from Thailand, the authors identified a SARS-CoV-2-related coronavirus (SC2r-CoV), designated as RacCS203, with 91.5% genome similarity to SARS-CoV-2, and show that sera obtained from bats and Malayan pangolin neutralize SARS-CoV-2.

• Supaporn Wacharapluesadee
• Chee Wah Tan
• Lin-Fa Wang

SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes

The SARS-CoV-2 gene set remains unresolved, hindering dissection of COVID-19 biology. Comparing 44 Sarbecovirus genomes provides a high-confidence protein-coding gene set. The study characterizes protein-level and nucleotide-level evolutionary constraints, and prioritizes functional mutations from the ongoing COVID-19 pandemic.

• Irwin Jungreis
• Rachel Sealfon
• Manolis Kellis

Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival

Antibody responses are critical for protection from developing severe COVID-19 following SARS-CoV-2 infection. Here the authors show that antibody responses against SARS-CoV-2 spike protein correlate with neutralizing capacity and protection, are not affected by heterologous boosting of influenza or common cold immunity, and can last up to 8 months.

• Stefania Dispinseri
• Massimiliano Secchi
• Gabriella Scarlatti

New-onset IgG autoantibodies in hospitalized patients with COVID-19

Infection with SARS-CoV2 and the development of Coronavirus disease 2019 (COVID-19) has been linked to induction of autoimmunity and autoantibody production. Here the authors characterise the new-onset IgG autoantibody response in hospitalised patients with COVID-19 which they correlate to the magnitude of the SARS-CoV2 response.

• Sarah Esther Chang
• Paul J. Utz

SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers

Several COVID-19 vaccines have shown good efficacy in clinical trials. Here, the authors provide real world effectiveness data in a group of BNT162b2 vaccinated health care workers and find that breakthrough infections are asymptomatic or mild.

• Francesca Rovida
• Irene Cassaniti
• Fausto Baldanti

Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Duration of infectious SARS-CoV-2 shedding is an important measure for improved disease control. Here, the authors use virus cultures of respiratory tract samples from COVID-19 patients and observe a median shedding duration of 8 days and a drop below 5% after 15,2 days post onset of symptoms.

• Jeroen J. A. van Kampen
• David A. M. C. van de Vijver
• Annemiek A. van der Eijk

A novel SARS-CoV-2 related coronavirus in bats from Cambodia

In this study, Delaune et al., isolate and characterise a SARS-CoV-2-related coronavirus from two bats sampled in Cambodia. Their findings suggest that the geographic distribution of SARS-CoV-2-related viruses is wider than previously reported.

• Deborah Delaune
• Veasna Duong

Neutralizing antibody titres in SARS-CoV-2 infections

Here, the authors perform plaque reduction neutralization (PRNT) assays quantitating SARS-CoV-2 specific neutralizing antibodies from 195 patients in different disease states and find that patients with severe disease exhibit higher peaks of neutralizing antibody titres than patients with mild or asymptomatic infections and that serum neutralizing antibody persists for over 6 months in most people.

• Eric H. Y. Lau
• Owen T. Y. Tsang
• Malik Peiris

SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

Vo’, Italy, is a unique setting for studying SARS-CoV-2 antibody dynamics because mass testing was conducted there early in the pandemic. Here, the authors perform two follow-up serological surveys and estimate seroprevalence, the extent of within-household transmission, and the impact of contact tracing.

• Ilaria Dorigatti
• Enrico Lavezzo
• Andrea Crisanti

Discrete SARS-CoV-2 antibody titers track with functional humoral stability

The extent of antibody protection against SARS-CoV-2 remains unclear. Here, using a cohort of 120 seroconverted individuals, the authors longitudinally characterize neutralization, Fc-function, and SARS-CoV-2 specific T cell responses, which they show to be prominent only in those subjects that elicited receptor-binding domain (RBD)-specific antibody titers above a certain threshold, suggesting that development of T cell responses to be related to anti-RBD Ab production.

• Yannic C. Bartsch
• Stephanie Fischinger
• Galit Alter

Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography

Shark antibodies (Variable New Antigen Receptors, VNARs) are the smallest naturally occurring antibody fragments. Here, the authors screen a VNAR phage display library against the SARS-CoV2 receptor binding domain (RBD) and identify VNARs that neutralize the SARSCoV-2 virus and discuss their mechanisms of viral neutralization.

• Obinna C. Ubah
• Eric W. Lake
• Caroline J. Barelle

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand

New Zealand has been relatively successful in controlling COVID-19 due to implementation of strict non-pharmaceutical interventions. Here, the authors demonstrate a striking decline in reports of influenza and other non-influenza respiratory pathogens over winter months in which the interventions have been in place.

• Q. Sue Huang
• Richard J. Webby

A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19

Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.

• Jiandong Huo
• Halina Mikolajek
• Raymond J. Owens

Reprogrammed CRISPR-Cas13b suppresses SARS-CoV-2 replication and circumvents its mutational escape through mismatch tolerance

Cas13b can be harnessed to target and degrade RNA transcripts inside a cellular environment. Here the authors reprogram Cas13b to target SARSCoV-2 transcripts in infected mammalian cells and reveal its resilience to variants thanks to single mismatch tolerance.

• Mohamed Fareh
• Joseph A. Trapani

SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells

T cells are instrumental to protective immune responses against SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Here the authors show that, in convalescent COVID-19 patients, memory T cell responses are detectable up to 317 days post-symptom onset, in which the presence of stem cell-like memory T cells further hints long-lasting immunity.

• Jae Hyung Jung
• Min-Seok Rha
• Eui-Cheol Shin

Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses

Long-term characterisation of SARS-CoV-2 antibody kinetics is needed to understand the protective role of the immune response. Here the authors describe antibody levels and neutralisation activity in healthcare workers over seven months and investigate the role of immunity to endemic human coronaviruses.

• Natalia Ortega
• Marta Ribes
• Carlota Dobaño

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir

Remdesivir is a nucleoside analog that inhibits the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and is used as a drug to treat COVID19 patients. Here, the authors provide insights into the mechanism of remdesivir-induced RdRp stalling by determining the cryo-EM structures of SARS-CoV-2 RdRp with bound RNA molecules that contain remdesivir at defined positions and observe that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation.

• Goran Kokic
• Hauke S. Hillen
• Patrick Cramer

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Covid 19 Essay in English

Essay on Covid -19: In a very short amount of time, coronavirus has spread globally. It has had an enormous impact on people's lives, economy, and societies all around the world, affecting every country. Governments have had to take severe measures to try and contain the pandemic. The virus has altered our way of life in many ways, including its effects on our health and our economy. Here are a few sample essays on ‘CoronaVirus’.

100 Words Essay on Covid 19

200 words essay on covid 19, 500 words essay on covid 19.

COVID-19 or Corona Virus is a novel coronavirus that was first identified in 2019. It is similar to other coronaviruses, such as SARS-CoV and MERS-CoV, but it is more contagious and has caused more severe respiratory illness in people who have been infected. The novel coronavirus became a global pandemic in a very short period of time. It has affected lives, economies and societies across the world, leaving no country untouched. The virus has caused governments to take drastic measures to try and contain it. From health implications to economic and social ramifications, COVID-19 impacted every part of our lives. It has been more than 2 years since the pandemic hit and the world is still recovering from its effects.

Since the outbreak of COVID-19, the world has been impacted in a number of ways. For one, the global economy has taken a hit as businesses have been forced to close their doors. This has led to widespread job losses and an increase in poverty levels around the world. Additionally, countries have had to impose strict travel restrictions in an attempt to contain the virus, which has resulted in a decrease in tourism and international trade. Furthermore, the pandemic has put immense pressure on healthcare systems globally, as hospitals have been overwhelmed with patients suffering from the virus. Lastly, the outbreak has led to a general feeling of anxiety and uncertainty, as people are fearful of contracting the disease.

My Experience of COVID-19

I still remember how abruptly colleges and schools shut down in March 2020. I was a college student at that time and I was under the impression that everything would go back to normal in a few weeks. I could not have been more wrong. The situation only got worse every week and the government had to impose a lockdown. There were so many restrictions in place. For example, we had to wear face masks whenever we left the house, and we could only go out for essential errands. Restaurants and shops were only allowed to operate at take-out capacity, and many businesses were shut down.

In the current scenario, coronavirus is dominating all aspects of our lives. The coronavirus pandemic has wreaked havoc upon people’s lives, altering the way we live and work in a very short amount of time. It has revolutionised how we think about health care, education, and even social interaction. This virus has had long-term implications on our society, including its impact on mental health, economic stability, and global politics. But we as individuals can help to mitigate these effects by taking personal responsibility to protect themselves and those around them from infection.

Effects of CoronaVirus on Education

The outbreak of coronavirus has had a significant impact on education systems around the world. In China, where the virus originated, all schools and universities were closed for several weeks in an effort to contain the spread of the disease. Many other countries have followed suit, either closing schools altogether or suspending classes for a period of time.

This has resulted in a major disruption to the education of millions of students. Some have been able to continue their studies online, but many have not had access to the internet or have not been able to afford the costs associated with it. This has led to a widening of the digital divide between those who can afford to continue their education online and those who cannot.

The closure of schools has also had a negative impact on the mental health of many students. With no face-to-face contact with friends and teachers, some students have felt isolated and anxious. This has been compounded by the worry and uncertainty surrounding the virus itself.

The situation with coronavirus has improved and schools have been reopened but students are still catching up with the gap of 2 years that the pandemic created. In the meantime, governments and educational institutions are working together to find ways to support students and ensure that they are able to continue their education despite these difficult circumstances.

Effects of CoronaVirus on Economy

The outbreak of the coronavirus has had a significant impact on the global economy. The virus, which originated in China, has spread to over two hundred countries, resulting in widespread panic and a decrease in global trade. As a result of the outbreak, many businesses have been forced to close their doors, leading to a rise in unemployment. In addition, the stock market has taken a severe hit.

Effects of CoronaVirus on Health

The effects that coronavirus has on one's health are still being studied and researched as the virus continues to spread throughout the world. However, some of the potential effects on health that have been observed thus far include respiratory problems, fever, and coughing. In severe cases, pneumonia, kidney failure, and death can occur. It is important for people who think they may have been exposed to the virus to seek medical attention immediately so that they can be treated properly and avoid any serious complications. There is no specific cure or treatment for coronavirus at this time, but there are ways to help ease symptoms and prevent the virus from spreading.

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Thousands Believe Covid Vaccines Harmed Them. Is Anyone Listening?

All vaccines have at least occasional side effects. But people who say they were injured by Covid vaccines believe their cases have been ignored.

Shaun Barcavage, 54, a nurse practitioner in New York City, said that ever since his first Covid shot, standing up has sent his heart racing. Credit... Hannah Yoon for The New York Times

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By Apoorva Mandavilli

Apoorva Mandavilli spent more than a year talking to dozens of experts in vaccine science, policymakers and people who said they had experienced serious side effects after receiving a Covid-19 vaccine.

• Published May 3, 2024 Updated May 4, 2024

Within minutes of getting the Johnson & Johnson Covid-19 vaccine, Michelle Zimmerman felt pain racing from her left arm up to her ear and down to her fingertips. Within days, she was unbearably sensitive to light and struggled to remember simple facts.

She was 37, with a Ph.D. in neuroscience, and until then could ride her bicycle 20 miles, teach a dance class and give a lecture on artificial intelligence, all in the same day. Now, more than three years later, she lives with her parents. Eventually diagnosed with brain damage, she cannot work, drive or even stand for long periods of time.

“When I let myself think about the devastation of what this has done to my life, and how much I’ve lost, sometimes it feels even too hard to comprehend,” said Dr. Zimmerman, who believes her injury is due to a contaminated vaccine batch .

The Covid vaccines, a triumph of science and public health, are estimated to have prevented millions of hospitalizations and deaths . Yet even the best vaccines produce rare but serious side effects . And the Covid vaccines have been given to more than 270 million people in the United States, in nearly 677 million doses .

Dr. Zimmerman’s account is among the more harrowing, but thousands of Americans believe they suffered serious side effects following Covid vaccination. As of April, just over 13,000 vaccine-injury compensation claims have been filed with the federal government — but to little avail. Only 19 percent have been reviewed. Only 47 of those were deemed eligible for compensation, and only 12 have been paid out, at an average of about $3,600 .

Some scientists fear that patients with real injuries are being denied help and believe that more needs to be done to clarify the possible risks.

“At least long Covid has been somewhat recognized,” said Akiko Iwasaki, an immunologist and vaccine expert at Yale University. But people who say they have post-vaccination injuries are “just completely ignored and dismissed and gaslighted,” she added.

In interviews and email exchanges conducted over several months, federal health officials insisted that serious side effects were extremely rare and that their surveillance efforts were more than sufficient to detect patterns of adverse events.

“Hundreds of millions of people in the United States have safely received Covid vaccines under the most intense safety monitoring in U.S. history,” Jeff Nesbit, a spokesman for the Department of Health and Human Services, said in an emailed statement.

But in a recent interview, Dr. Janet Woodcock, a longtime leader of the Food and Drug Administration, who retired in February, said she believed that some recipients had experienced uncommon but “serious” and “life-changing” reactions beyond those described by federal agencies.

“I feel bad for those people,” said Dr. Woodcock, who became the F.D.A.’s acting commissioner in January 2021 as the vaccines were rolling out. “I believe their suffering should be acknowledged, that they have real problems, and they should be taken seriously.”

“I’m disappointed in myself,” she added. “I did a lot of things I feel very good about, but this is one of the few things I feel I just didn’t bring it home.”

Federal officials and independent scientists face a number of challenges in identifying potential vaccine side effects.

The nation’s fragmented health care system complicates detection of very rare side effects, a process that depends on an analysis of huge amounts of data. That’s a difficult task when a patient may be tested for Covid at Walgreens, get vaccinated at CVS, go to a local clinic for minor ailments and seek care at a hospital for serious conditions. Each place may rely on different health record systems.

There is no central repository of vaccine recipients, nor of medical records, and no easy to way to pool these data. Reports to the largest federal database of so-called adverse events can be made by anyone, about anything. It’s not even clear what officials should be looking for.

“I mean, you’re not going to find ‘brain fog’ in the medical record or claims data, and so then you’re not going to find” a signal that it may be linked to vaccination, Dr. Woodcock said. If such a side effect is not acknowledged by federal officials, “it’s because it doesn’t have a good research definition,” she added. “It isn’t, like, malevolence on their part.”

The government’s understaffed compensation fund has paid so little because it officially recognizes few side effects for Covid vaccines. And vaccine supporters, including federal officials, worry that even a whisper of possible side effects feeds into misinformation spread by a vitriolic anti-vaccine movement.

‘I’m Not Real’

Patients who believe they experienced serious side effects say they have received little support or acknowledgment.

Shaun Barcavage, 54, a nurse practitioner in New York City who has worked on clinical trials for H.I.V. and Covid, said that ever since his first Covid shot, merely standing up sent his heart racing — a symptom suggestive of postural orthostatic tachycardia syndrome , a neurological disorder that some studies have linked to both Covid and, much less often, vaccination .

He also experienced stinging pain in his eyes, mouth and genitals, which has abated, and tinnitus, which has not.

“I can’t get the government to help me,” Mr. Barcavage said of his fruitless pleas to federal agencies and elected representatives. “I am told I’m not real. I’m told I’m rare. I’m told I’m coincidence.”

Renee France, 49, a physical therapist in Seattle, developed Bell’s palsy — a form of facial paralysis, usually temporary — and a dramatic rash that neatly bisected her face. Bell’s palsy is a known side effect of other vaccines, and it has been linked to Covid vaccination in some studies.

But Dr. France said doctors were dismissive of any connection to the Covid vaccines. The rash, a bout of shingles, debilitated her for three weeks, so Dr. France reported it to federal databases twice.

“I thought for sure someone would reach out, but no one ever did,” she said.

Similar sentiments were echoed in interviews, conducted over more than a year, with 30 people who said they had been harmed by Covid shots. They described a variety of symptoms following vaccination, some neurological, some autoimmune, some cardiovascular.

All said they had been turned away by physicians, told their symptoms were psychosomatic, or labeled anti-vaccine by family and friends — despite the fact that they supported vaccines.

Even leading experts in vaccine science have run up against disbelief and ambivalence.

Dr. Gregory Poland, 68, editor in chief of the journal Vaccine, said that a loud whooshing sound in his ears had accompanied every moment since his first shot, but that his entreaties to colleagues at the Centers for Disease Control and Prevention to explore the phenomenon, tinnitus, had led nowhere.

He received polite responses to his many emails, but “I just don’t get any sense of movement,” he said.

“If they have done studies, those studies should be published,” Dr. Poland added. In despair that he might “never hear silence again,” he has sought solace in meditation and his religious faith.

Dr. Buddy Creech, 50, who led several Covid vaccine trials at Vanderbilt University, said his tinnitus and racing heart lasted about a week after each shot. “It’s very similar to what I experienced during acute Covid, back in March of 2020,” Dr. Creech said.

Research may ultimately find that most reported side effects are unrelated to the vaccine, he acknowledged. Many can be caused by Covid itself.

“Regardless, when our patients experience a side effect that may or may not be related to the vaccine, we owe it to them to investigate that as completely as we can,” Dr. Creech said.

Federal health officials say they do not believe that the Covid vaccines caused the illnesses described by patients like Mr. Barcavage, Dr. Zimmerman and Dr. France. The vaccines may cause transient reactions, such as swelling, fatigue and fever, according to the C.D.C., but the agency has documented only four serious but rare side effects .

Two are associated with the Johnson & Johnson vaccine, which is no longer available in the United States: Guillain-Barré syndrome , a known side effect of other vaccines , including the flu shot; and a blood-clotting disorder.

The C.D.C. also links mRNA vaccines made by Pfizer-BioNTech and Moderna to heart inflammation, or myocarditis, especially in boys and young men. And the agency warns of anaphylaxis, or severe allergic reaction, which can occur after any vaccination.

Listening for Signals

Agency scientists are monitoring large databases containing medical information on millions of Americans for patterns that might suggest a hitherto unknown side effect of vaccination, said Dr. Demetre Daskalakis, director of the C.D.C.’s National Center for Immunization and Respiratory Diseases.

“We toe the line by reporting the signals that we think are real signals and reporting them as soon as we identify them as signals,” he said. The agency’s systems for monitoring vaccine safety are “pretty close” to ideal, he said.

Those national surveillance efforts include the Vaccine Adverse Event Reporting System (VAERS). It is the largest database, but also the least reliable: Reports of side effects can be submitted by anyone and are not vetted, so they may be subject to bias or manipulation.

The system contains roughly one million reports regarding Covid vaccination, the vast majority for mild events, according to the C.D.C.

Federal researchers also comb through databases that combine electronic health records and insurance claims on tens of millions of Americans. The scientists monitor the data for 23 conditions that may occur following Covid vaccination. Officials remain alert to others that may pop up, Dr. Daskalakis said.

But there are gaps, some experts noted. The Covid shots administered at mass vaccination sites were not recorded in insurance claims databases, for example, and medical records in the United States are not centralized.

“It’s harder to see signals when you have so many people, and things are happening in different parts of the country, and they’re not all collected in the same system,” said Rebecca Chandler, a vaccine safety expert at the Coalition for Epidemic Preparedness Innovations.

An expert panel convened by the National Academies concluded in April that for the vast majority of side effects, there was not enough data to accept or reject a link.

Asked at a recent congressional hearing whether the nation’s vaccine-safety surveillance was sufficient, Dr. Peter Marks, director of the F.D.A.’s Center for Biologics Evaluation and Research, said, “I do believe we could do better.”

In some countries with centralized health care systems, officials have actively sought out reports of serious side effects of Covid vaccines and reached conclusions that U.S. health authorities have not.

In Hong Kong, the government analyzed centralized medical records of patients after vaccination and paid people to come forward with problems. The strategy identified “a lot of mild cases that other countries would not otherwise pick up,” said Ian Wong, a researcher at the University of Hong Kong who led the nation’s vaccine safety efforts.

That included the finding that in rare instances — about seven per million doses — the Pfizer-BioNTech vaccine triggered a bout of shingles serious enough to require hospitalization.

The European Medicines Agency has linked the Pfizer and Moderna vaccines to facial paralysis, tingling sensations and numbness. The E.M.A. also counts tinnitus as a side effect of the Johnson & Johnson vaccine, although the American health agencies do not. There are more than 17,000 reports of tinnitus following Covid vaccination in VAERS.

Are the two linked? It’s not clear. As many as one in four adults has some form of tinnitus. Stress, anxiety, grief and aging can lead to the condition, as can infections like Covid itself and the flu.

There is no test or scan for tinnitus, and scientists cannot easily study it because the inner ear is tiny, delicate and encased in bone, said Dr. Konstantina Stankovic, an otolaryngologist at Stanford University.

Still, an analysis of health records from nearly 2.6 million people in the United States found that about 0.04 percent , or about 1,000, were diagnosed with tinnitus within three weeks of their first mRNA shot. In March, researchers in Australia published a study linking tinnitus and vertigo to the vaccines .

The F.D.A. is monitoring reports of tinnitus, but “at this time, the available evidence does not suggest a causal association with the Covid-19 vaccines,” the agency said in a statement.

Despite surveillance efforts, U.S. officials were not the first to identify a significant Covid vaccine side effect: myocarditis in young people receiving mRNA vaccines. It was Israeli authorities who first raised the alarm in April 2021. Officials in the United States said at the time that they had not seen a link.

On May 22, 2021, news broke that the C.D.C. was investigating a “relatively few” cases of myocarditis. By June 23, the number of myocarditis reports in VAERS had risen to more than 1,200 — a hint that it is important to tell doctors and patients what to look for.

Later analyses showed that the risk for myocarditis and pericarditis, a related condition, is highest after a second dose of an mRNA Covid vaccine in adolescent males aged 12 to 17 years.

In many people, vaccine-related myocarditis is transient. But some patients continue to experience pain, breathlessness and depression, and some show persistent changes on heart scans . The C.D.C. has said there were no confirmed deaths related to myocarditis, but in fact there have been several accounts of deaths reported post-vaccination .

Pervasive Misinformation

The rise of the anti-vaccine movement has made it difficult for scientists, in and out of government, to candidly address potential side effects, some experts said. Much of the narrative on the purported dangers of Covid vaccines is patently false, or at least exaggerated, cooked up by savvy anti-vaccine campaigns.

Questions about Covid vaccine safety are core to Robert F. Kennedy Jr.’s presidential campaign. Citing debunked theories about altered DNA, Florida’s surgeon general has called for a halt to Covid vaccination in the state.

“The sheer nature of misinformation, the scale of misinformation, is staggering, and anything will be twisted to make it seem like it’s not just a devastating side effect but proof of a massive cover-up,” said Dr. Joshua Sharfstein, a vice dean at Johns Hopkins University.

Among the hundreds of millions of Americans who were immunized for Covid, some number would have had heart attacks or strokes anyway. Some women would have miscarried. How to distinguish those caused by the vaccine from those that are coincidences? The only way to resolve the question is intense research .

But the National Institutes of Health is conducting virtually no studies on Covid vaccine safety, several experts noted. William Murphy, a cancer researcher who worked at the N.I.H. for 12 years, has been prodding federal health officials to initiate these studies since 2021.

The officials each responded with “that very tired mantra: ‘But the virus is worse,’” Dr. Murphy recalled. “Yes, the virus is worse, but that doesn’t obviate doing research to make sure that there may be other options.”

A deeper understanding of possible side effects, and who is at risk for them, could have implications for the design of future vaccines, or may indicate that for some young and healthy people, the benefit of Covid shots may no longer outweigh the risks — as some European countries have determined.

Thorough research might also speed assistance to thousands of Americans who say they were injured.

The federal government has long run the National Vaccine Injury Compensation Program , designed to compensate people who suffer injuries after vaccination. Established more than three decades ago, the program sets no limit on the amounts awarded to people found to have been harmed.

But Covid vaccines are not covered by that fund because Congress has not made them subject to the excise tax that pays for it. Some lawmakers have introduced bills to make the change.

Instead, claims regarding Covid vaccines go to the Countermeasures Injury Compensation Program . Intended for public health emergencies, this program has narrow criteria to pay out and sets a limit of $50,000, with stringent standards of proof.

It requires applicants to prove within a year of the injury that it was “the direct result” of getting the Covid vaccine, based on “compelling, reliable, valid, medical, and scientific evidence.”

The program had only four staff members at the beginning of the pandemic, and now has 35 people evaluating claims. Still, it has reviewed only a fraction of the 13,000 claims filed, and has paid out only a dozen.

Dr. Ilka Warshawsky, a 58-year-old pathologist, said she lost all hearing in her right ear after a Covid booster shot. But hearing loss is not a recognized side effect of Covid vaccination.

The compensation program for Covid vaccines sets a high bar for proof, she said, yet offers little information on how to meet it: “These adverse events can be debilitating and life-altering, and so it’s very upsetting that they’re not acknowledged or addressed.”

Dr. Zimmerman, the neuroscientist, submitted her application in October 2021 and provided dozens of supporting medical documents. She received a claim number only in January 2023.

In adjudicating her claim for workers’ compensation, Washington State officials accepted that Covid vaccination caused her injury, but she has yet to get a decision from the federal program.

One of her therapists recently told her she might never be able to live independently again.

“That felt like a devastating blow,” Dr. Zimmerman said. “But I’m trying not to lose hope there will someday be a treatment and a way to cover it.”

Apoorva Mandavilli is a reporter focused on science and global health. She was a part of the team that won the 2021 Pulitzer Prize for Public Service for coverage of the pandemic. More about Apoorva Mandavilli

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A and B, Histologic findings in an adult man with severe cardiac magnetic resonance imaging abnormalities 67 days after COVID-19 diagnosis. High-sensitivity troponin T level on the day of cardiac magnetic resonance imaging was 16.7 pg/mL. The patient recovered at home from COVID-19 illness with minimal symptoms, which included loss of smell and taste and only mildly increased temperature lasting 2 days. There were no known previous conditions or regular medication use. Histology revealed intracellular edema as enlarged cardiomyocytes with no evidence of interstitial or replacement fibrosis. Panels A and B show immunohistochemical staining, which revealed acute lymphocytic infiltration (lymphocyte function–associated antigen 1 and activated lymphocyte T antigen CD45R0) as well as activated intercellular adhesion molecule 1. C to F, Representative cardiac magnetic resonance images of an adult woman with COVID-19–related perimyocarditis. Panels C and D show significantly raised native T1 and native T2 in myocardial mapping acquisitions. Panels E and F show pericardial effusion and enhancement (yellow arrowheads) and epicardial and intramyocardial enhancement (white arrowheads) in late gadolinium enhancement (LGE) acquisition.

There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 (median [interquartile range], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P  = .008) and high-sensitivity troponin T (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P  = .002) but not for native T2 or N-terminal pro–b-type natriuretic peptide. For the coronavirus disease 2019 (COVID-19) home recovery group, dark circles indicate symptomatic illness and light circles indicate asymptomatic illness. Boxes indicate overlays of box-whisker plots, midlines indicate medians, and whiskers indicate the farthest data point not regarded as an outlier (ie, within 1.5-fold the interquartile range).

There was no significant correlation with duration between the positive test for COVID-19 and the measures (native T1: r  = 0.07; P  = .47; native T2: r  = 0.14; P  = .15; high-sensitivity troponin T: r  = −0.07; P  = .50). The trend line indicates the linear regression trend, and the shaded area indicates 95% CIs of the mean.

eFigure. STROBE diagram

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• Coronavirus Disease 2019 (COVID-19) and the Heart JAMA Cardiology Editorial November 1, 2020 Clyde W. Yancy, MD, MSc; Gregg C. Fonarow, MD
• Errors in Statistical Numbers and Data in Study of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From COVID-19 JAMA Cardiology Comment & Response November 1, 2020 Eike Nagel, MD; Valentina O. Puntmann, MD, PhD
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Puntmann VO , Carerj ML , Wieters I, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265–1273. doi:10.1001/jamacardio.2020.3557

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Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

• 1 Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, University Hospital Frankfurt, Frankfurt am Main, Germany
• 2 Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy
• 3 Department of Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany
• 4 Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt am Main, Germany
• 5 Department of Cardiology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
• 6 Department of Hospital Therapy No. 1, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
• 7 Institute for Cardiac Diagnostic and Therapy, Berlin, Germany
• Editorial Coronavirus Disease 2019 (COVID-19) and the Heart Clyde W. Yancy, MD, MSc; Gregg C. Fonarow, MD JAMA Cardiology
• Medical News & Perspectives Younger Adults Cautioned to Take COVID-19 Seriously as Demographics Shift Jennifer Abbasi JAMA
• Medical News & Perspectives JAMA Network Articles of the Year 2020 Jennifer Abbasi JAMA
• Medical News & Perspectives Researchers Investigate What COVID-19 Does to the Heart Jennifer Abbasi JAMA
• Comment & Response Errors in Statistical Numbers and Data in Study of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From COVID-19 Eike Nagel, MD; Valentina O. Puntmann, MD, PhD JAMA Cardiology
• Correction Errors in Statistical Numbers and Data JAMA Cardiology
• Comment & Response Cardiac Involvement After Recovering From COVID-19 Łukasz A. Małek, MD, PhD JAMA Cardiology
• Comment & Response Cardiac Involvement After Recovering From COVID-19 Laura Filippetti, MD; Nathalie Pace, MD; Pierre-Yves Marie, MD, PhD JAMA Cardiology

Question   What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?

Findings   In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.

Meaning   These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Importance   Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.

Objective   To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.

Design, Setting, and Participants   In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.

Exposure   Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract.

Main Outcomes and Measures   Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57).

Results   Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P  = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P  = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r  = 0.07; P  = .47; native T2: r  = 0.14; P  = .15; hsTnT: r  = −0.07; P  = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping ( r  = 0.33; P  < .001) and native T2 mapping ( r  = 0.18; P  = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology.

Conclusions and Relevance   In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

The global pandemic of coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. 1 Thus far, the main emphasis of the research communication has been on acute respiratory complications, especially in critically ill patients. A number of case reports and small series suggested that COVID-19 prominently affects the cardiovascular system by exacerbating heart failure in patients with preexisting cardiac conditions 1 - 3 and troponin elevation in critically ill patients. 4 Fulminant myocarditis was suspected in 7% of patients with lethal outcome. 5 Quiz Ref ID The proposed pathophysiological mechanisms of cardiac injury include inflammatory plaque rupture, stent thrombosis, cardiac stress due to high cardiac output, and infection via the angiotensin-converting enzyme 2 receptors causing systemic endothelitis. 6 , 7 A small number of autopsy cases suggest infiltration by interstitial mononuclear inflammatory cells, 8 suggesting myocardial inflammation as the underlying mechanism, and some severe cases of myocarditis have been reported. 3 , 9 In a small study of recovered patients with ongoing cardiac symptoms, cardiovascular magnetic resonance (CMR) imaging revealed cardiac involvement in 58% of patients consisting of myocardial edema and scar by late gadolinium enhancement (LGE). 10 There remains poor insight into the cardiovascular sequelae in unselected patients, including those with no preexisting conditions, who were not hospitalized, or had no or only mild symptoms. To better understand the prevalence, extent, and type of cardiovascular sequelae, we proactively examined patients with a documented recent COVID-19 infection using serological markers of cardiac injury and highly standardized in-depth imaging with CMR.

This is a prospective observational cohort study of 100 patients diagnosed with severe acute respiratory syndrome coronavirus 2 by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract who fulfilled inclusion criteria for this CMR investigation. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline (eFigure in the Supplement ). Participants were identified from the University Hospital Frankfurt COVID-19 Registry via the Department of Infectious Diseases and the Institute for Experimental and Translational Cardiovascular Imaging, Hesse, Germany, and were recruited between April and June 2020. All participants were considered eligible after a minimum of 2 weeks from the original diagnosis if they had resolution of respiratory symptoms and negative results on a swab test at the end of the isolation period. Patients recently recovered from COVID-19 referred for a clinical CMR due to active cardiac symptoms were not included in this analysis. Exclusion criteria were unwillingness to participate or provide informed consent or absolute contraindications for a contrast-enhanced magnetic resonance study. The study protocol was approved by the institutional ethics committee of the University Hospital Frankfurt (Improving Cardiovascular Risk Stratification Using T1 Mapping in General Population study 11 ). Comparisons were made with age-matched and sex-matched control groups of normotensive adults who were taking no cardiac medications, had normal cardiac volumes and function, and had no evidence of scar (healthy controls; n = 50). Comparisons were also made with risk factor–matched patients (n = 57) for age, sex, hypertension, diabetes, smoking, known coronary artery disease, or comorbidities, sourced from the International T1 Multicenter Outcome Study. 12 All procedures were performed in concordance with the Declaration of Helsinki and International Conference on Harmonization of Good Clinical Practice. All patients provided written informed consent.

Clinical demographic characteristics, medications, blood test results, endomyocardial biopsy results, and imaging measurements on the day of CMR examination were recorded using REDCap electronic data capture tools. 13 All participants underwent venous blood sampling immediately prior to the CMR study. Blood samples were processed using standardized commercially available test kits for analysis of high-sensitivity troponin T (hsTnT) and N-terminal pro–b-type natriuretic peptide (Elecsys 2010; Roche). The local laboratory cutoff value for detectable hsTnT was greater than 3 pg/mL, whereas values above the 99th percentile (13.9 pg/mL) counted as a significant increase. 14

Cardiac magnetic resonance imaging was performed on clinical 3-T scanners (Magnetom Skyra; Siemens Healthineers), using standardized and unified imaging protocols (Goethe CVI Approaches). Conventional sequences were used for acquisition of cardiac function, volumes, mass, and scar imaging. Myocardial T1 and T2 mapping were acquired in a single midventricular short-axis slice using a validated variant of a modified Look-Locker Imaging sequence (Goethe CVI MOLLI), whereas for T2 mapping, a validated sequence for measurement of myocardial edema was used (T2-FLASH). 15 - 17 Due to the proven sensitivity of Goethe CVI MOLLI for abnormal myocardium and evidence of superior diagnostic and prognostic performance, 18 postcontrast T1 mapping was not part of the standardized protocol. Late gadolinium enhancement imaging was performed approximately 10 minutes after administration of 0.1 mmol/kg of body weight of gadobutrol (Gadovist; Bayer).

Cardiac volumes, function, and mass were measured using an artificial intelligence–based automated contour detection with manual correction if required (SuiteHeart; Neosoft). Myocardial T1 and T2 relaxation times were measured conservatively within the septal myocardium of the midventricular SAX slice using motion-corrected images, as per internal standardized operating procedures 19 and with quality control by the core laboratory staff, blinded to the underlying clinical information using pseudonymized data sets. Areas of LGE were excluded from the measurements to avoid confounding diffuse fibrosis with replacement scar. Interpretation of LGE images followed standardized postprocessing recommendations; myocardial LGE was visually defined by 2 observers based on the presence and predominant pattern as ischemic or nonischemic. 20 Pericardial LGE was considered present when enhancement involved both pericardial layers, irrespective of the presence of pericardial effusion. The distinction from the pericardial fat was ascertained using T1 mapping images.

Normality of distributions were tested using Shapiro-Wilk test. Categorical data are presented as counts (percentages) and continuous variables as means (standard deviation) and medians (interquartile ranges [IQRs]). Comparisons between patients’ groups were conducted using one-way analysis of variance for normally distributed parameters and Kruskal-Wallis for nonnormally distributed data with post hoc tests for significance between groups. Fischer exact and χ 2 tests were used for proportions. Receiver operating characteristic curve analyses were used to examine discrimination (expressed as area under the receiver operating characteristic curve) between patients recently recovered from COVID-19 and control groups. Associations were explored using Pearson or Spearman correlation analyses, as appropriate for the type of data. Abnormal native T1 and T2 values were defined as greater than 1105 ms and greater than 37.4 ms, respectively, based on previously derived sequence-specific cutoffs of 2 SDs above the respective means in a healthy population. 18 , 21 , 22 Significant abnormalities were defined as greater than 1136 ms for T1 and greater than 40 ms for T2, using 4 SDs above those means. Classification into abnormal and significantly abnormal served to distinguish the patients with a potential high risk of adverse events. 23 , 24 All tests were 2-tailed, and P values less than .05 were considered statistically significant. Analysis was performed using SPSS software version 25.0 (IBM) and RStudio version 1.2.5001 (RStudio).

An unselected cohort of 100 patients who recently recovered from COVID-19 infection were included, of which 53 (53%) were male, and the mean (SD) age was 49 (14) years. Baseline characteristics are provided in Table 1 . Most patients recovered at home (n = 67), with severity of the acute COVID-19 illness ranging from asymptomatic (n = 18) to minor to moderate symptoms (n = 49). A total of 33 severely unwell patients (33%) required hospitalization. In this group, 2 patients (2%) underwent mechanical ventilation, and 17 (17%) underwent noninvasive ventilation with positive airway pressure. Oxygen supplementation was required in 28 patients. In addition to respiratory support, patients received antiviral (n = 1), antibiotic (n = 15), and steroid (n = 8) therapy. Treatment with hydrochloroquine was initiated in a single patient but discontinued within days due to severe leukopenia. During hospitalization, a significant rise (greater than 13.9 pg/mL) in hsTnT values was documented in 15 patients (15%). Preexisting cardiovascular conditions included hypertension, diabetes, and known coronary artery disease but no previously known heart failure or cardiomyopathy. Other significant conditions included asthma (n = 10) and chronic obstructive pulmonary disease (n = 11). All preexisting conditions were similarly distributed between patients who recovered at home vs hospitalized.

Patient characteristics and the results of the imaging parameters and blood markers on the day of CMR are shown in Table 1 . Body mass index, hypertension, diabetes, hypercholesterolemia, known coronary artery disease, and chronic obstructive pulmonary disease or asthma were associated with COVID-19 diagnosis compared with the healthy controls, but there were no differences between those with COVID-19 and the risk factor–matched patients. The median (IQR) duration between the positive COVID-19 testing and the CMR examination was 71 (64-92) days. On the day of CMR examination, direct questioning about symptoms revealed atypical chest pain (n = 17) and palpitations (n = 20). Compared with pre–COVID-19 status, 36 patients (36%) reported ongoing shortness of breath and general exhaustion, of whom 25 noted symptoms during less-than-ordinary daily activities, such as a household chore. Only 4 of these 25 patients (16%) were previously hospitalized. No patient reported typical angina symptoms or a recent syncope. High-sensitivity troponin T values were detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular and right ventricular ejection fraction, higher left ventricular volume, and raised native T1 and T2 measures. A total of 78 patients recently recovered from COVID-19 had abnormal CMR findings, including at least one of the following: raised myocardial native T1 (n = 73), 21 raised myocardial native T2 (n = 60), 22 myocardial LGE (n = 32), or pericardial enhancement (n = 22) ( Figure 1 ). A total of 12 patients recently recovered from COVID-19 had an ischemic-type pattern of myocardial LGE. Three patients with severe abnormalities (significantly higher hsTnT, native T1, and native T2 measures, LGE, and left ventricular ejection fraction less than 50%) were referred to endomyocardial biopsy, revealing active lymphocytic inflammation with no evidence of any viral genome. Figure 2 and Figure 3 show the findings for native T1 and T2 mapping and hsTnT values based on the COVID-19 illness presentation (home-based recovery vs hospitalization) and in relation to the time from the original COVID-19 diagnosis. There was a significant difference between patients who recovered at home vs in the hospital for native T1 measures (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P  = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P  = .002) but not for native T2 or N-terminal pro–b-type natriuretic peptide. There was no significant correlation with duration between the positive test for COVID-19 and the measures (native T1: r  = 0.07; P  = .47; native T2: r  = 0.14; P  = .15; hsTnT: r  = −0.07; P  = .50) ( Figure 3 ). High-sensitivity troponin T was significantly correlated with native T1 ( r  = 0.33; P  < .001), native T2 ( r  = 0.18; P  = .01), and left ventricle mass ( r  = 0.25; P  = .01). There was also a cross-correlation between native T1 and T2 ( r  = 0.40; P  < .001). The associations of hsTnT with mapping measures remained significant despite controlling for the presence of comorbidities (overall or separately) or treatment received during the COVID-19 illness.

Table 2 shows the results of the receiver operating characteristic curve analyses for discrimination between the control groups and patients recently recovered from COVID-19 using imaging measures and blood biomarkers. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology.

A total of 78 patients who recovered from COVID-19 infection (78%) had cardiovascular involvement as detected by standardized CMR, irrespective of preexisting conditions, the severity and overall course of the COVID-19 presentation, the time from the original diagnosis, or the presence of cardiac symptoms. Quiz Ref ID The most prevalent abnormality was myocardial inflammation (defined as abnormal native T1 and T2 measures), detected in 60 patients recently recovered from COVID-19 (60%), followed by regional scar and pericardial enhancement. Findings on classic parameters, such as volumes and ejection fractions, were mildly abnormal. Myocardial measures, native T1 measures, and native T2 measures provided the best discriminatory value against healthy controls and risk factor–matched controls for exclusion of any myocardial disease or confirmation of COVID-19–related involvement, respectively.

To our knowledge, this is the first prospective report on a cohort of unselected patients with a recent COVID-19 infection identified from a local testing center who voluntarily underwent evaluation for cardiac involvement with CMR. The results of our study provide important insights into the prevalence of cardiovascular involvement in the early convalescent stage. Our findings demonstrate that participants with a relative paucity of preexisting cardiovascular condition and with mostly home-based recovery had frequent cardiac inflammatory involvement, which was similar to the hospitalized subgroup with regards to severity and extent. Our observations are concordant with early case reports in hospitalized patients showing a frequent presence of LGE, 3 , 25 diffuse inflammatory involvement, 10 , 26 and significant rise of troponin T levels. 4 Unlike these previous studies, our findings reveal that significant cardiac involvement occurs independently of the severity of original presentation and persists beyond the period of acute presentation, with no significant trend toward reduction of imaging or serological findings during the recovery period. Our findings may provide an indication of potentially considerable burden of inflammatory disease in large and growing parts of the population and urgently require confirmation in a larger cohort. Although the long-term health effects of these findings cannot yet be determined, several of the abnormalities described have been previously related to worse outcome in inflammatory cardiomyopathies. 27 - 29 Quiz Ref ID Most imaging findings point toward ongoing perimyocarditis after COVID-19 infection. This is further confirmed by the cross-correlation between the T1 and T2 measures and hsTnT as well as histological verification of inflammatory changes in more severe cases.

Each of the abnormal imaging parameters can be linked to an underlying pathophysiological process and worse outcome. The peri-epicardial LGE in the areas with increased contrast agent uptake represents regional damage due to myocardial inflammation. Especially in combination with pericardial effusion, these observations can be attributed to fibrosis and/or edema due to an ongoing active pericarditis. Nonischemic patterns of myocardial LGE are mainly observed in patients with acute or healed myocarditis and have been strongly linked to reduced outcome. 23 , 24 , 30 , 31 Quiz Ref ID Increased native T1 measures represent diffuse myocardial fibrosis and/or edema, whereas native T2 is specific for edema. 18 Thus, patients with increased native T1 and T2 measures have an active inflammatory process, while those with increased native T1 and normal native T2 measures have healed with some residual diffuse myocardial damage (although native T1 measures can be increased in a variety of pathophysiology, as many different pathways lead to diffuse fibrosis, including hypertension or genetic cardiomyopathies). Yet the combination with histological findings as well as the increase relative to age-matched, sex-matched, and risk factor–matched controls makes a COVID-19–related inflammatory process as the underlying pathophysiology highly likely. Increased native T1 measures have been strongly related to worse outcome in patients with ischemic heart disease and nonischemic cardiomyopathies. 23 , 24 , 30 , 31 Increased troponin T and C-reactive protein levels similarly indicate inflammatory and partially ongoing myocardial damage and have been related to worse outcome, even if only minimally increased. 32 Quiz Ref ID While left and right ventricular ejection fraction were significantly reduced, there was a large overlap between patients recently recovered from COVID-19 and both control groups, demonstrating that volumes and function are inferior markers of disease detection compared with direct tissue characterization with mapping measures. Importantly, volumes and function have consistently been demonstrated to be less relevant for predicting outcome than LGE and mapping, highlighting the relevance of the more sensitive markers of early cardiac damage. 23 , 24 , 30 , 31

Our study has limitations. The findings are not validated for the use in pediatric patients 18 years and younger. They also do not represent patients during acute COVID-19 infection or those who are completely asymptomatic with COVID-19. Several patients within our cohort had new or persistent symptoms, thus increasing the likelihood of positive CMR findings. Outcome data remain outstanding. The imaging sequences used in this study have been well validated, standardized, and locked for the use in multicenter settings. The use of other imaging protocols, sequence parameters, or postprocessing approaches may yield different results.

Taken together, we demonstrate cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%) with recent COVID-19 illness, independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Accepted for Publication: July 6, 2020.

Published Online: July 27, 2020. doi:10.1001/jamacardio.2020.3557

Correction: This article was corrected on August 25, 2020, to fix pervasive errors in statistical numbers and data in the Abstract, Methods and Results sections, Tables, and Figures 1 and 2.

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2020 Puntmann VO et al. JAMA Cardiology .

Corresponding Author: Eike Nagel, MD, Institute for Experimental and Translational Cardiovascular Imaging, DZHK Centre for Cardiovascular Imaging, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany ( [email protected] ).

Author Contributions: Drs Puntmann and Nagel had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design : Puntmann, Shchendrygina, Vasa-Nicotera, Zeiher, Nagel.

Acquisition, analysis, or interpretation of data : Puntmann, Carerj, Wieters, Fahim, Arendt, Hoffmann, Escher, Vehreschild, Nagel.

Drafting of the manuscript : Puntmann, Shchendrygina, Nagel.

Critical revision of the manuscript for important intellectual content : Puntmann, Carerj, Wieters, Fahim, Arendt, Hoffmann, Escher, Vasa-Nicotera, Zeiher, Vehreschild, Nagel.

Statistical analysis : Puntmann, Nagel.

Obtained funding : Puntmann, Zeiher, Nagel.

Administrative, technical, or material support : Puntmann, Carerj, Wieters, Fahim, Arendt, Escher, Vehreschild, Nagel.

Study supervision : Puntmann, Wieters, Arendt, Vasa-Nicotera, Vehreschild, Nagel.

Conflict of Interest Disclosures: Dr Escher has received personal fees from Institut Kardiale Diagnostik und Therapie outside the submitted work. Dr Zeiher has received grants from the German Centre for Cardiovascular Research during the conduct of the study and personal fees from Sanofi, Amgen, Boehringer Ingelheim, and Novo Nordisk outside the submitted work. Dr Vehreschild has received grants from BioNTech and Takeda outside the submitted work. Dr Nagel has received grants from Bayer, the German Ministry for Education and Research, Deutsche Herzstiftung e.V., Neosoft Technologies, and Cardio-Pulmonary Institute and personal fees from Bayer. No other disclosures were reported.

Funding/Support: Drs Puntmann, Arendt, Escher, Vasa-Nicotera, Zeiher, and Nagel were supported by grants from the German Ministry of Education and Research via the German Centre for Cardiovascular Research (DZHK) partner site RheinMain, Deutsche Herzstiftung e.V., Bayer, and Cardio-Pulmonary Institute

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We acknowledge the dedicated support of clinical research support staff of the Institute of Experimental and Translational Cardiovascular Imaging, including Tammy Wolf, Thourier Azdad, Franziska Weis, Deniz Desik, BA, and Layla Laghchioua, MSc, as well as of the Department of Infectious Diseases, University Hospital Frankfurt. We are very grateful to our colleagues of the Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany, for treating all critically ill patients with COVID-19. Contributors were not compensated for their work.

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Ivan Specht decided to employ his love of math during pandemic, which led to contact-tracing app, papers, future path

Part of the commencement 2024 series.

A collection of stories covering Harvard University’s 373rd Commencement.

Ivan Specht started at Harvard on track to study pure mathematics. But when COVID-19 sent everyone home, he began wishing the math he was doing had more relevance to what was happening in the world.

Specht, a New York City native, expanded his coursework, arming himself with statistical modeling classes, and began to “fiddle around” with simulating ways diseases spread through populations. He got hooked. During the pandemic, he became one of only two undergraduates to serve on Harvard’s testing and tracing committee, eventually developing a prototype contact-tracing app called CrimsonShield.

Specht took his curiosity for understanding disease propagation to the lab of computational geneticist Pardis Sabeti , professor in Organismic and Evolutionary Biology at Harvard and member of the Broad Institute, known for her work sequencing the Ebola virus in 2014 . Specht, now a senior, has since co-authored several studies around new statistical methods for analyzing the spread of infectious diseases, with plans to continue that work in graduate school.

“Ivan is absolutely brilliant and a joy to work with, and his research accomplishments already as an undergraduate are simply astounding,” Sabeti said. “He is operating at the level of a seasoned postdoc.”

His senior thesis, “Reconstructing Viral Epidemics: A Random Tree Approach,” described a statistical model aimed at tackling one of the most intractable problems that plague infectious disease researchers: determining who transmitted a given pathogen to whom during a viral outbreak. Specht was co-advised by computer science Professor Michael Mitzenmacher, who guided the statistical and computational sections of his thesis, particularly in deriving genomic frequencies within a host using probabilistic methods.

Specht said the pandemic made clear that testing technology could provide valuable information about who got sick, and even what genetic variant of a pathogen made them sick. But mapping paths of transmission was much more challenging because that process was completely invisible. Such information, however, could provide crucial new details into how and where transmission occurred and be used to test things such as vaccine efficacy or the effects of closing schools. 

Specht’s work exploited the fact that viruses leave clues about their transmission path in their phylogenetic trees, or lines of evolutionary descent from a common ancestor. “It turns out that genome sequences of viruses provide key insight into that underlying network,” said the joint mathematics and statistics concentrator.

Uncovering this transmission network goes to the heart of how single-stranded RNA pathogens survive: Once they infect their host, they mutate, producing variants that are marked by slightly different genetic barcodes. Specht’s statistical model determines how the virus spreads by tracking the frequencies of different viral variants observed within a host.  

As the centerpiece of his thesis, he reconstructed a dataset of about 45,000 SARS-CoV-2 genomes across Massachusetts, providing insights into how outbreaks unfolded across the state.

Specht will take his passion for epidemiological modeling to graduate school at Stanford University, with an eye toward helping both researchers and communities understand and respond to public health crises.

A graphic designer with experience in scientific data visualization, Specht is focused not only on understanding outbreaks, but also creating clear illustrations of them. For example, his thesis contains a creative visual representation of those 45,000 Massachusetts genomes, with colored dots representing cases, positioned nearby other “dots” they are likely to have infected.

Specht’s interest in graphics began in middle school when, as an enthusiast of trains and mass transit, he started designing imagined subway maps for cities that lack actual subways, like Austin, Texas . At Harvard, he designed an interactive “subway map” depicting a viral outbreak.

As a member of the Sabeti lab, Specht taught an infectious disease modeling course to master’s and Ph.D. students at University of Sierra Leone last summer. His outbreak analysis tool is also now being used in an ongoing study of Lassa fever in that region. And he co-authored two chapters of a textbook on outbreak science in collaboration with the Moore Foundation.

Over the past three years, Specht has been lead author of a paper in Scientific Reports and another in Cell Patterns , and co-author on two others, including a cover story in Cell . His first lead-author paper, “The case for altruism in institutional diagnostic testing,” showed that organizations like Harvard should allocate COVID-19 testing capacity to their surrounding communities, rather than monopolize it for themselves. That work was featured in The New York Times .

During his time at Harvard, Specht lived in Quincy House and was design editor of the Harvard Advocate, the University’s undergraduate literary magazine. In his free time he also composes music, and he still considers himself a mass transit enthusiast.

In the acknowledgements section of his thesis, he credited Sabeti with opening his eyes to the “many fascinating problems at the intersection of math, statistics, and computational biology.”

“I could fill this entire thesis with reasons I am grateful for Professor Sabeti, but I think they can be summarized by the sense of wonder and inspiration I feel every time I set foot in her lab.”

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AstraZeneca pulls its COVID-19 vaccine from the European market

FILE - Medical staff prepares an AstraZeneca coronavirus vaccine during preparations at the vaccine center in Ebersberg near Munich, Germany, Monday, March 22, 2021. The pharma giant AstraZeneca has requested that its European authorization for its COVID vaccine be pulled, according to the EU medicines regulator on Wednesday, May 8, 2024. (AP Photo/Matthias Schrader, FILE)

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LONDON (AP) — The pharma giant AstraZeneca has requested that the European authorization for its COVID-19 vaccine be pulled, according to the EU medicines regulator.

In an update on the European Medicines Agency’s website Wednesday, the regulator said that the approval for AstraZeneca’s Vaxzevria had been withdrawn “at the request of the marketing authorization holder.”

AstraZeneca’s COVID-19 vaccine was first given the nod by the EMA in January 2021 . Within weeks, however, concerns grew about the vaccine’s safety, when dozens of countries suspended the vaccine’s use after unusual but rare blood clots were detected in a small number of immunized people. The EU regulator concluded AstraZeneca’s shot didn’t raise the overall risk of clots, but doubts remained.

Partial results from its first major trial — which Britain used to authorize the vaccine — were clouded by a manufacturing mistake that researchers didn’t immediately acknowledge. Insufficient data about how well the vaccine protected older people led some countries to initially restrict its use to younger populations before reversing course.

Billions of doses of the AstraZeneca vaccine were distributed to poorer countries through a U.N.-coordinated program, as it was cheaper and easier to produce and distribute. But studies later suggested that the pricier messenger RNA vaccines made by Pfizer-BioNTech and Moderna provided better protection against COVID-19 and its many variants, and most countries switched to those shots.

The U.K.'s national coronavirus immunization program in 2021 heavily relied on AstraZeneca’s vaccine, which was largely developed by scientists at Oxford University with significant financial government support. But even Britain later resorted to buying the mRNA vaccines for its COVID booster vaccination programs and the AstraZeneca vaccine is now rarely used globally.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.