Two years of pandemic: A wealth of data and many remaining questions
Authors: Sara Hamilton, Isabel Goldman, Kristan van der Vos, Sha Yu
Journal: Cell Reports Medicine (2022)

This month marks 2 years since the World Health Organization declared COVID-19 a global pandemic on March 11, 2020. Few of us imagined what would follow. Over the past 2 years, SARS-CoV-2 has infected almost half a billion people, 5.9 million have died, and millions more are now dealing with the long-term impact of the virus and the pandemic. The ongoing waves of infection continue to overburden our healthcare systems. Despite ongoing lab closures and systemic healthcare disruptions, the global scientific community has made incredible advances in understanding the underlying biology of the virus, how the host immune system responds to the virus, as well as how COVID-19 manifests. We have also made rapid progress in treating COVID-19 patients and in developing effective vaccines and antiviral therapies: over 10 million vaccine doses have been administered in the last year. Despite this progress, the pandemic’s end is not in sight, and we continue to deal with emerging variants and the growing problems of long COVID. Additionally, COVID has illuminated longstanding health inequities that remain challenging to address. In this issue, we spotlight some of the scientists and clinicians who have been working tirelessly on or amid the ongoing pandemic, on the advances that have been made, and on the questions that have emerged as we reach this milestone. In a series of Q&A's, Kristen Noble (pp. 100567), Wendy Kennette (pp. 100565), Ken Pang (pp. 100568), Pamela Klein (pp. 100566), and Hugh Taylor (pp. 100569) each describe the challenges and changes that COVID-19 restrictions brought to their practices and discuss what changes are here to stay. In their minireview, Katherine Kedzierska and Paul Thomas (pp. 100562) outline what we have learned about T cell responses following SARS-CoV-2 infection and vaccination. We also feature a series of Commentaries focusing on many of the active and emerging questions around the virus and the pandemic. George Gao and colleagues (Wang et al., pp. 100524) describe a canine coronavirus isolated from human patients and discuss the implications of this for understanding the zoonotic potential of other emerging coronaviruses. Tiannan Guo and co-authors outline how multi-omics technologies have advanced our understanding of SARS-CoV-2 biology and the impact of infection on our health (Lu et al., pp. 100580). They also discuss some of the challenges that limit the application of these approaches to patient management and clinical decision-making. Edy Kim and colleagues (Lee et al., pp. 100533) walk us through the evolving care of COVID-19 patients and how clinicians adapted from the early absence of clear clinical guidance during a healthcare crisis to integrating new approaches and innovations as they have become available. Manmeet Singh and Emmie de Wit (pp. 100549) discuss the successes and challenges associated with the development and use of antiviral therapies to treat COVID-19. Nina Langeland and others (Blomberg et al., pp. 100552) describe the growing problem of long COVID and its impact on public health and healthcare services. They point to the urgent need for treatments and interventions. Paolo Palma and collaborators (Amodio et al., pp. 100558) look at pediatric infections and why children tend to experience a milder disease. Laura White and colleagues (White et al., pp. 100556) review the current data around the impact that children and schools have on driving the spread of SARS-CoV-2 variants, as well as the current evidence for safely operating schools to minimize transmission. In the face of the growing imbalance in the global distribution of COVID-19 vaccines, Amrish Baidjoe and colleagues (Van der Graaf et al., pp. 100551) discuss the concept of vaccine equity within the broader context of systemic health inequities. They ask us to consider the historical and socio-political contributions that have led to this imbalance and discuss the importance of using the momentum from this pandemic to correct these systemic inequities. We round off the focus issue with four Research Articles that further our understanding of SARS-CoV-2 and COVID-19. Giamarellos-Bourboulis et al. (pp. 100560) introduce and validate the SCOPE score, which can predict severe respiratory failure in COVID-19 pneumonia. Bolze et al. (pp. 100564) sequence 74,348 SARS-CoV-2 samples collected across the US to show that Delta rapidly became the dominant variant by displacing Alpha, Gamma, Iota, and Mu. Mahdad Noursadeghi and co-authors (Chandran et al., pp. 100557) find that rapid, synchronous type 1 IFN and virus-specific T cell responses characterize first-wave non-severe SARS-CoV-2 infections, suggesting the importance of targeting early T cell mediated heterologous protection in next-generation vaccines. And finally, Penny Moore and colleagues (Kitchin et al., pp. 100535) find that breakthrough infection after vaccination with the Janssen (Johnson & Johnson) Ad26.COV2.S vaccine boosts neutralizing antibody titers against Omicron. This collection makes clear a few common themes. First, the incredible scientific achievements our communities have made toward ending the pandemic and the speed at which data and information have been generated, shared, and acted on to address this global crisis are truly unprecedented. Secondly, COVID-19 is a disease that has disproportionally impacted marginalized communities and for which we have witnessed uneven vaccine distribution. These twin realities have laid bare longstanding healthcare inequities across the globe. Collectively addressing the structural imbalances that allow these inequities to continue is of paramount importance. And, finally, this collection explores how we can apply the lessons we have learned to better address the lasting impact of COVID-19 as well as to thwart future pandemics. We have yet to realize the full impact of the pandemic on our health and society, but the collective focus on this shared problem presents us with an opportunity that we must not waste. Pamela Klein (she/her) et al.Cell Reports MedicineMarch 15, 2022In BriefPamela Klein, Nurse Manager of Transgender Services at Boston Health Care for the Homeless Program (BHCHP) and Nurse Liaison for Boston Medical Center (BMC)’s Center for Transgender Medicine and Surgery (CTMS), shares how the COVID-19 pandemic has affected her practice and her patients and reflects on which changes in care she believes will become permanent. Full-Text PDF Open AccessCount on us: T cells in SARS-CoV-2 infection and vaccinationKedzierska et al.Cell Reports MedicineFebruary 24, 2022In BriefKedzierska and Thomas review CD8+ and CD4+ T cell responses following SARS-CoV-2 infection and vaccination. They discuss epitope-specific T cell responses during acute disease, persistence into long-term memory, and cross-reactivity toward variants of concern. Full-Text PDF Open AccessLong COVID: A growing problem in need of interventionBlomberg et al.Cell Reports MedicineFebruary 13, 2022In BriefThe number of people who have survived COVID-19 is overwhelming—official figures approach half a billion ( https://covid19.who.int ). Thus, any long-term consequences in COVID-19 survivors could have a huge impact on public health and on healthcare services in the coming months and years, with potentially 100 million individuals affected. Full-Text PDF Open AccessThe role of schools in driving SARS-CoV-2 transmission: Not just an open-and-shut caseWhite et al.Cell Reports MedicineFebruary 18, 2022In BriefKeeping schools open without permitting COVID-19 spread has been complicated by conflicting messages around the role of children and schools in fueling the pandemic. Here, we describe methodological limitations of research minimizing SARS-CoV-2 transmission in schools, and we review evidence for safely operating schools while reducing overall SARS-CoV-2 transmission. Full-Text PDF Open AccessAd26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concernKitchin et al.Cell Reports MedicineFebruary 9, 2022In BriefKitchin, Richardson et al. show that responses to Ad26.COV2.S persist for 6 months after vaccination. Furthermore, mild breakthrough infection after Ad26.COV2.S vaccination results in dramatic boosts in binding and neutralizing antibody titers and Fc effector function. This includes high titers of neutralizing antibodies against the highly resistant Omicron variant. Full-Text PDF Open AccessVaccine equity: Past, present, and futurevan der Graaf et al.Cell Reports MedicineFebruary 10, 2022In BriefThe term “vaccine equity” primarily points to the enormous imbalance in global COVID-19 vaccine distribution. Vaccine equity should adopt a normative approach toward “health equity,” and various stakeholders across the vaccine life cycle must practice it. The momentum gathered during this pandemic must be used to correct these structural imbalances. Full-Text PDF Open AccessKristen Noble et al.Cell Reports MedicineMarch 15, 2022In BriefEven in the NICU, the COVID pandemic has changed our clinical practices and impacted our ability to care for patients and their families. From increased premature births to new challenges engaging parents in the care of their children, we have employed major adaptations to the way we care for patients. Full-Text PDF Open AccessMore efforts are needed for background surveys of zoonotic coronaviruses in animalsWang et al.Cell Reports MedicineMarch 15, 2022In BriefRecently, a novel dog-origin coronavirus has been found in humans. The low similarity between the receptor-binding domain from this novel virus and other human-infecting coronaviruses in genus Alphacoronavirus suggests it might use a novel receptor or mechanism to enter human cells and also might trigger a novel immune response. Full-Text PDF Open AccessCOVID-19 in children: From afterthought to unknownAmodio et al.Cell Reports MedicineMarch 15, 2022In BriefChildren were initially considered unsusceptible to severe COVID-19. Our knowledge after two years has changed dramatically, but there are still many unknowns. Here, we report the current knowledge about why children generally experience a milder COVID-19 course and highlight research questions about pediatric infection that require answers. Full-Text PDF Open AccessRapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infectionsChandran et al.Cell Reports MedicineMarch 4, 2022In BriefNon-severe SARS-CoV-2 infection in unvaccinated virus-naive individuals may reveal correlates of protection against future variants. In this context, Chandran et al. show rapid type 1 interferon and virus-specific T cell responses 1–2 weeks before virus-specific antibodies, supporting a role for T cell-mediated heterologous protection in next-generation vaccines. Full-Text PDF Open AccessDevelopment and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failureGiamarellos-Bourboulis et al.Cell Reports MedicineFebruary 24, 2022In BriefGiamarellos-Bourboulis et al. introduce the SCOPE score for early prognostication of the risk for severe respiratory failure or death within the next 14 days in COVID-19 pneumonia. This is composed of C-reactive protein, D dimers, ferritin, and interleukin-6 concentrations. Anakinra treatment administered when SCOPE is 6 or more provides lower odds of a poor outcome. Full-Text PDF Open AccessAntiviral agents for the treatment of COVID-19: Progress and challengesSingh et al.Cell Reports MedicineFebruary 10, 2022In BriefThe COVID-19 pandemic has seen clinical development and use of antiviral therapies at an unprecedented speed. Antiviral therapies have greatly improved the clinical outcome in COVID-19 patients, especially when administered early after diagnosis. Here, we discuss the successes and challenges of COVID-19 antiviral therapies and lessons for future pandemics. Full-Text PDF Open AccessTreating COVID-19: Evolving approaches to evidence in a pandemicLee et al.Cell Reports MedicineFebruary 8, 2022In BriefThe rapid pace of the COVID-19 pandemic precluded traditional approaches to evaluating clinical research and guidelines. We highlight notable successes and pitfalls of clinicians’ new approaches to managing evidence amidst an unprecedented crisis. In “Era 1 (early 2020),” clinicians relied on anecdote and social media, which democratized conversations on guidelines, but also led clinicians astray. “Era 2 (approximately late 2020 to early 2021)” saw preprints that accelerated new interventions but suffered from a surfeit of poor-quality data. In the current era, clinicians consolidate the evidentiary gains of Era 2 with living, online clinical guidelines, but the public suffers from misinformation. The COVID-19 pandemic is a laboratory on how clinicians adapt to an absence of clinical guidance amidst an informational and healthcare crisis. Challenges remain as we integrate new approaches to innovations made in the traditional guideline process to confront both the long tail of COVID-19 and future pandemics. Full-Text PDF Open AccessHugh Taylor et al.Cell Reports MedicineMarch 15, 2022In BriefHugh Taylor shares some of his experiences as a Family Medicine physician through the COVID-19 pandemic and how these have impacted his life and practice over time. Full-Text PDF Open AccessKen C. Pang et al.Cell Reports MedicineMarch 15, 2022In BriefKen C. Pang is an Australian physician scientist whose pediatric practice focuses on the care of transgender children and adolescents. During the pandemic, his clinical practice has largely shifted to telehealth-based consultations, which have brought both positive and negative changes. Full-Text PDF Open AccessSARS-CoV-2 variant Delta rapidly displaced variant Alpha in the United States and led to higher viral loadsBolze et al.Cell Reports MedicineMarch 15, 2022In BriefBolze et al. show that the Delta variant of SARS-CoV-2 rapidly grew to become the dominant variant by July 2021 in the United States. Delta displaced variants of concern Alpha and Gamma and the variants of interest Iota and Mu. Full-Text PDF Open AccessWendy Kennette et al.Cell Reports MedicineMarch 15, 2022In BriefWendy Kennette shares some of her experiences practicing as a palliative medicine physician through the COVID-19 pandemic and how her practice and personal life have adapted over time. Full-Text PDF Open Access