To support urgent research to combat the ongoing outbreak of COVID-19, caused by the novel coronavirus SARS-CoV-2, the editorial teams at Nature Research have curated a collection of relevant articles. Our collection includes research into the basic biology of coronavirus infection, its detection, treatment and evolution, research into the epidemiology of emerging viral diseases, and our coverage of current events. The articles will remain free to access for as long as the outbreak remains a public health emergency of international concern.
Latest SARS-CoV-2/COVID-19 research
Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions
Estimating the effects of non-pharmaceutical interventions for COVID-19 is challenging, partly due to variations in testing. Here, the authors use viral sequence data as an alternative means of inferring intervention effects, and show that delays in implementation resulted in more severe epidemics.
Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19.
GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein
Coronavirus nucleocapsid (N) protein is important for viral genome packaging and virion assembly. Here the authors show that natural chemical (-)-gallocatechin gallate (GCG) disrupts the liquid–liquid phase separation of N and inhibits SARS-CoV-2 replication.
Seroprevalence and correlates of SARS-CoV-2 neutralizing antibodies from a population-based study in Bonn, Germany
Population-based studies of SARS-CoV-2 seroprevalence are needed to understand levels of immunity and antibody dynamics. Here, the authors show that the seroprevalence in Bonn, Germany was low (<1%) following the first epidemic wave, and that neutralising antibodies waned within a few months.
IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals
Our understanding of the immune response to SARS-CoV-2 infection is still incomplete. Here, the authors find that IL-33, produced during immune recall potentially by CD14+ monocytes, correlates with CD4+ T cell activation, anti-SARS-CoV-2 antibody titer, and disease severity in a cohort of convalescent individuals professionally exposed to the virus.
T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses
Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.
Virus-specific antibody levels after a single dose of the BNT162b2 vaccine in individuals previously infected with SARS-CoV-2 are similar to levels after two doses of the vaccine in infection-naive individuals.
Systems serology detects functionally distinct coronavirus antibody features in children and elderly
Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.
The essential SARS-CoV-2 3CL protease is of interest as a drug target. Here, the authors identify three 3CL inhibitors and characterize them both in vitro and with a cell-based assay, and they also present the inhibitor-bound 3CL crystal structures, which may allow for the design of improved compounds.
Breakthrough infections of SARS-CoV-2 occurring 12 or more days after the first dose of the BNT162b2 mRNA vaccine were associated with lower viral loads than those found in unvaccinated individuals, suggesting that the vaccine might reduce infectiousness.
Serological detection of antibodies against SARS-CoV-2 can help establish rates of seroconversion. Here the authors develop a red cell agglutination test to detect antibodies against the receptor binding domain for distribution free of charge to qualified research groups.
Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England
Many countries have closed schools as part of their COVID-19 response. Here, the authors model SARS-CoV-2 transmission on a network of schools and households in England, and find that risk of transmission between schools is lower if primary schools are open than if secondary schools are open.
Sera from convalescent individuals with coronavirus disease 2019 and from individuals vaccinated with BNT162b2 have reduced ability to neutralize SARS-CoV-2 variants B1.1.7 and B.1.351, but antibody potency against the variants increases after two vaccine doses.
COVID-19 has caused many healthcare systems to become overwhelmed, potentially impacting patient care. Here, the authors show that COVID-19-related in-hospital mortality rates in Israel increased in periods of moderate or high hospital load, independent of patient characteristics.
N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection
Here the authors develop a single molecule array (Simoa) immunoassay for detection of SARS-CoV-2 nucleocapsid protein in venous and dried capillary blood as well as saliva. The assay shows good performance in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals.
The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.
Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.
SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19
A better understanding of longitudinal changes in antibody responses in COVID-19 patients is needed. Here the authors analyze anti-spike and anti-nucleocapsid antibody responses to Sars-CoV-2 over a course of 6 months in a large cohort of patients with COVID-19, showing that IgM is mostly not detectable after 3 months, whereas IgG responses contract, yet remain at high levels at 6 months.
A homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies
Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.
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.
Here, via screening of a polypeptide library from bronchoalveolar lavage, the authors identify and characterize α1-antitrypsin (α1AT) as SARS-CoV-2 inhibitor and show that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion.
An engineered CRISPR-Cas12a variant and DNA-RNA hybrid guides enable robust and rapid COVID-19 testing
As the COVID-19 pandemic continues, variants of the virus are emerging. Here the authors present a diagnostic assay that can detect wildtype and known variants using engineered Cas12a.
A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies
Here, the authors report the isolation and characterization of two human monoclonal antibodies (mAbs) from immunized mice with trimeric spike ectodomains of three human betacoronaviruses HCoV-OC43, SARS-CoV and MERSCoV, and show that while exhibiting cross-reactivity, the mAbs only neutralize MERS-CoV but not SARS-CoV nor SARS-CoV-2, likely due to the subtle epitope differences in the spike S2 fusion subunit.
The anti-leprosy drug clofazimine inhibits coronavirus replication in several cell models and shows potent antiviral activity against SARS-CoV-2 infection in a hamster model, particularly when used in combination with remdesivir.
ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity
ISG15 conjugation is essential to activate the RIG-I-like receptor MDA5 and trigger antiviral responses. SARS-CoV-2 suppresses MDA5 activation by direct PLpro-mediated de-ISGylation to escape innate immunity.
Analysis of community-tested cases of SARS-CoV-2 indicates that the B.1.1.7 variant is not only more transmissible than pre-existing variants, but may also cause more severe illness, and is associated with a higher risk of death.
Viruses rely on host metabolism for replication. Here, the authors perform transcriptional and metabolomic analyses at 8 hours after SARS-CoV-2 infection and find that the virus alters host folate and one-carbon metabolism at a post-transcriptional level.
News and Comment
Letter to the Editor
Climate change can both facilitate zoonotic spillovers and have an effect on transmission chains. These effects, alongside human behavior and awareness, need to be integrated in pandemic forecasting models.
Taiwan has leveraged its experience in containing the 2003 SARS outbreak by responding to the COVID-19 crisis with rapid measures, early deployment, prudent actions and transparency. Collectively, these actions have created the ‘Taiwan model’ for combating COVID-19.
Policymakers need insight from humanities and social sciences to tackle the pandemic.
The COVID-19 pandemic has reasserted the central role of effective diagnostics in the response to outbreaks. But a lack of coordination still hampers widespread access to these critical tools. A diagnostics agenda for global health is urgently needed for the promotion of diagnostics as a global good and to ensure their delivery.
The COVID-19 pandemic should revive a shared understanding of humanitarian emergencies and crisis resolution, opening the door to transformative change in humanitarian responses. But it has also revealed political opportunism and poor data-reporting structures.
Investigations show that those spreading misinformation that undermines the rollout of vaccines against COVID-19 are well financed, determined and disciplined. To counter their activities, we need to understand them as an industry actively working to sow doubts about the deadliness of COVID-19, vaccines and medical professionals’ integrity.
In the midst of resurging COVID-19 cases, the second NIH/FDA virtual COVID-19 and Cytokines symposium was held on 1 December 2020, focusing on longitudinal studies of COVID-19 immunity, including long-term consequences, potential associations with autoimmunity and the multisystem inflammatory syndrome in children (MIS-C).
Reviews and Perspectives
Examination of the vaccine strategies and technical platforms used for the COVID-19 pandemic in the context of those used for previous emerging and reemerging infectious diseases and pandemics can offer critical lessons to prepare for future public health emergencies.
A comprehensive review of the current literature on post-acute COVID-19, also referred to as long COVID, its pathophysiology and its organ-specific sequelae highlights the need for multidisciplinary follow-up and care of COVID-19 survivors.
In this Review, Leung provides an overview of the transmissibility and modes of transmission of respiratory viruses, the viral, host and environmental determinants of transmission, and common non-pharmaceutical interventions for mitigating respiratory virus transmission. She also discusses the recent controversies over aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.
Global coordination of public health efforts will be needed to defeat the COVID-19 pandemic and to prepare for future public health emergencies.
All countries worldwide have signed up to the United Nations Sustainable Development Goals and committed to the objective of achieving universal health coverage. Getting there will require understanding how packages of essential health services can be developed in resource-constrained settings and how experts and the public can make decisions about which health services should be provided free of charge.
Recent advances in computational and laboratory sciences are helping researchers to address large-scale sustained emergencies, such as the COVID-19 pandemic, and constantly adapt to the emergence of new questions, data and findings in order to synthesize real-time evidence that will inform policy decisions.
A timeline of the major scientific discoveries during the first year of the COVID-19 pandemic showcases the collaborative efforts that enabled the key aspects of the immune response to SARS-CoV-2 to be reported at unprecedented speed.
This Review provides mechanistic and clinical insights into COVID-19 in the context of liver disease, discussing the potential underlying biology and clinical features of SARS-CoV-2 infection in patients with pre-existing liver conditions. The management of these patients is also discussed, including SARS-CoV-2 vaccination strategies.
This Review highlights how obesity and impaired metabolic health increase complications and mortality in coronavirus disease 2019 (COVID-19) and summarizes the consequences of infection with severe acute respiratory syndrome coronavirus 2 for organ function. In addition, there is a discussion on the implications of the COVID-19 pandemic for the obesity pandemic.
Although COVID-19 is a respiratory disease and its causative agent, SARS-CoV-2, principally infects the respiratory tract, extrapulmonary manifestations are observed. This Perspective explores the gastrointestinal symptoms associated with COVID-19 and the putative underlying mechanisms, discussing experimental evidence on SARS-COV-2 gastrointestinal infection and the potential for faecal–oral transmission.
Unique biological traits of bats and adaptive evolution associated with flight confer immunotolerance of viral infection that may help to make bats special reservoir hosts for viruses.
A comprehensive strategy for the next steps to ensure vaccination of the global population against SARS-CoV-2 is now required, and key steps and challenges are detailed in this Perspective.
Computational approaches for drug repurposing can accelerate the identification of treatments during a pandemic. In this Review, the authors discuss this topic in the context of COVID-19 and propose a strategy to make computational drug repurposing more effective in future pandemics.
The severity of COVID-19 varies by sex and age, and is linked to comorbidities. Differences in immune reactions may go some way to explain this.
Advances made in synthesis and analytical techniques has allowed the exploration and mimicry of natural materials. Resilin-mimetics have emerged from this advance as a biomaterial with a range of potential applications. Here, the authors review the history and current research on resilin-mimetics, providing a future perspective.