Vaccines for SARS-CoV-2 are needed to fight the pandemic. Here the authors show immunogenicity of an adjuvanted subunit vaccine, SARS-CoV-2 spike protein trimerized with trimer-tag technology, in small animal models and protection from SARS-CoV-2 challenge in non-human primates.
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
Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19
Statins, which have anti-inflammatory and antithrombotic properties, could have effects in COVID-19 patients. Here, the authors find in a retrospective analysis of patients hospitalized with COVID-19 that antecedent statin use is associated with lower inpatient mortality.
A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
A variant of the OAS1 gene, which encodes an enzyme that is critical for the innate immune response to viral infections, is associated with decreased risk of death in patients with COVID-19.
Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.
Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients
SARS-CoV2 infection has been linked to a wide range of clinical severities and the immunopathology is still under intense scrutiny. Here, the authors uncover an association of antibody affinity maturation and plasma IgA levels with clinical outcome in patients with COVID-19 disease.
Exploring beyond clinical routine SARS-CoV-2 serology using MultiCoV-Ab to evaluate endemic coronavirus cross-reactivity
Serology is an important way to monitor SARS-CoV-2 infection in the population and support vaccine development. Here the authors develop a multiplex immunoassay including spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses with high specificity and sensitivity.
Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.
Harnessing peak transmission around symptom onset for non-pharmaceutical intervention and containment of the COVID-19 pandemic
Transmission by pre-symptomatic and asymptomatic viral carriers makes intervention and containment of the COVID-19 extremely challenging. Here, the authors construct an epidemiological model that focuses on transmission around the symptom onset, exploring specific transmission control measures.
Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.
Childhood infection with SARS CoV2 is associated with a milder course of infection but the immunopathogenesis of this remains unclear. Here the authors explore immunological differences in the innate immune system during acute and convalescent SARS CoV2 infection in the young.
The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.
Social distancing policies aiming to reduce COVID-19 transmission have been reflected in reductions in human mobility. Here, the authors show that reduced mobility is correlated with decreased transmission, but that this relationship weakened over time as social distancing measures were relaxed.
The role of children in the spread of COVID-19 is not fully understood, and the circumstances under which schools should be opened are therefore debated. Here, the authors demonstrate protocols by which schools in France can be safely opened without overwhelming the healthcare system.
A study of multisystem inflammatory syndrome in children (MIS-C) shows maintenance of elevated levels of monocyte-activating pathogen-specific IgG not seen in children infected with SARS-CoV-2 who do not develop MIS-C.
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.
Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody
Here, using the K18-hACE2 transgenic mice model, the authors report the in vivo efficacy of a fully human neutralizing antibody against SARS-CoV-2 and show that when administered before or up to 3 days post infection, treated mice do not exhibit disease symptoms while 80% of control animals succumb to the infection.
The SARS-CoV-2 spike protein contains a multi-basic cleavage site. Here, the authors show how this multi-basic cleavage site affects entry of SARS-CoV-2 into cells and transmission in the hamster model and identify host factors affecting entry of SARS-CoV-2 in a genome-wide CRISPR screen.
During the early phase of the COVID-19 pandemic there was a need for rapid dissemination of clinical findings. Here, Jung, Di Santo et al. perform a systematic review and cohort study providing evidence for lower methodological quality scores and faster time to publication of clinical studies related to COVID-19 than comparable studies.
Dexamethasone has been shown to have survival benefits for critically ill patients hospitalised with COVID-19 in the UK. Here, the authors estimated the number of lives that could be saved through a UK and global roll out of the drug and demonstrate that it is a cost-effective option.
REACT-2 is a large-scale community study of SARS-CoV-2 seroprevalence in England. Here, the authors estimate that 6% of adults in England had been infected by mid-July 2020, with health and long-term care workers and those of Black or South Asian ethnicity disproportionately affected.
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.
Physical distancing measures have been widely adopted to reduce the spread of COVID-19. This study quantifies changes in interpersonal contact patterns in the US and finds an 82% reduction in contacts during early lockdowns in March and steady increases thereafter.
Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera
Human sera from recipients of the BNT162b2 vaccine can neutralize SARS-CoV-2 viruses containing spike mutations present in globally circulating variants of concern.
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.
Spread of SARS-CoV-2 in the early phase of the pandemic has been driven by high population susceptibility, but virus sensitivity to climate may play a role in future outbreaks. Here, the authors simulate SARS-CoV-2 dynamics in winter assuming climate dependence is similar to an endemic coronavirus strain.
The societal response to the pandemic has reduced global power demand, disproportionally affecting coal power generation and thus leading to a strong CO2 emissions decline. Policy should apply 2020’s lessons to ensure that power sector emissions have peaked in 2018 and go into structural decline.
SARS-CoV-2 D614G spike protein mutation is one of the predominant circulating vital mutants. Here, Ozono et al. demonstrate that D614G mutation increases in vitro cell entry by acquiring higher affinity to ACE2.
Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide
Enzalutamide, an approved drug for prostate cancer, acts on TMPRSS2 expression, a key mediator for SARS-CoV-2 infection. Here, the authors characterize the anti-SARS-CoV-2 effects of Enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and in hACE2-transduced Tmprss2 knockout mice and show lack antiviral action in human lung cells and human lung organoids, likely due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells.
The authors describe a reverse genetic system that enables rapid synthesis of wild-type, mutant and reporter SARS-CoV-2 strains to study viral infection, transmission, pathogenesis, therapeutics and vaccines.
A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication
Here, using in vitro assays and structural analysis, the authors characterize the anti-SARS-CoV-2 properties of two small molcules, showing these to bind and target the virus main protease (Mpro), and to exhibit a synergistic antiviral effect when combined with remdesivir in vitro.
The COVID-19 epidemic began later in Russia than many European countries, possibly due to restrictions on travel from China. Here, the authors analyze whole genome sequences sampled early in the epidemic in Russia, and find that most strains were not linked to China.
Patients with mild COVID-19 show a pattern of interferon-stimulated gene (ISG) expression across all major cell types, but in patients with severe disease, antibodies block the production of these ISG-expressing cells.
Experimental deletion of the furin cleavage site of the SARS-CoV-2 spike protein highlights an important role for this site in infection and the need to consider this site when evaluating the neutralization activities of antibodies.
Induction of CD4 T follicular helper (Tfh) cells is important for antibody responses to viral infections. Here, the authors show in a rhesus macaque model of mild COVID-19 that SARS-CoV-2 infection results in transient accumulation of proliferating Tfh cells with a Th1 profile in peripheral blood and generation of germinal center Tfh cells specific for viral proteins.
A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Vaccines for SARS-COV-2 are needed in the ongoing pandemic. Here the authors characterize a vaccine candidate that presents the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on a synthetic VLP platform using SpyTag/SpyCatcher technology and show immunogenicity of a prime-boost regimen in mice and pigs.
The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein
The SARS-CoV-2 nucleocapsid (N) protein binds the viral RNA genome and contains two ordered domains flanked by three intrinsically-disordered regions. Here, the authors show that RNA binding induces liquid-liquid phase separation of N, which is driven by its central intrinsically-disordered region and is modulated by phosphorylation. The SARS-CoV-2 Membrane (M) protein also phase-separates with N, and three-component mixtures of N + M + RNA form mutually exclusive compartments containing N + M or N + RNA.
Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. Here, Ku et al., identify SARS-CoV-2 neutralizing antibodies from a phage library and identify an antibody combination that prevents viral escape and protects mice from viral challenge.
Genomic epidemiology of SARS-CoV-2 reveals multiple lineages and early spread of SARS-CoV-2 infections in Lombardy, Italy
The Lombardy region of Italy was heavily affected early in the SARS-CoV-2 pandemic. Here, the authors use whole genome sequencing and show that there were multiple introductions into the region, with transmission occurring before the first case was detected.
In a cohort of 87 individuals with COVID-19, the memory B cell response at 6.2 months after the onset of disease evolves in a manner that is consistent with the persistence of SARS-CoV-2 antigen.
Incidence of COVID-19 has been high in parts of South America including Brazil, and information on effective intervention strategies is needed. Here, the authors use mathematical modelling to show that reductions in social distancing should be made gradually to avoid a severe second peak of cases.
News and Comment
Somewhat surprisingly, individuals with asthma do not seem to have a greater risk of developing severe COVID-19. Here, the authors offer mechanistic insights to explain the epidemiological data.
Studies to promote uptake are as essential as research to develop vaccines.
Patients with kidney diseases should be prioritized for COVID-19 vaccination and the available data suggest that replication-defective viral-vectored vaccines and mRNA vaccines are safe to use. As vaccine responses are likely to be lower in patients with kidney diseases than in the general population, highly potent vaccines should be preferred.
Diverging from tested vaccination regimens without scientific evidence could undermine public confidence in vaccines against COVID-19 and the success of a global vaccination strategy to curtail the pandemic.
Barber shops, churches, libraries — that’s where researchers must go to tackle inequity.
The COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, poses a clear and present danger to the health and well-being of populations. Here we discuss its indirect impact on global cancer prevention and control efforts, particularly for cervical cancer. We suggest some comparisons between the COVID-19 pandemic and the human papillomavirus–induced cancer burden, as well as opportunities for translating pandemic-control strategies into effective cancer control.
Reviews and Perspectives
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.
As the world races to develop vaccines against SARS-CoV-2, Dai and Gao highlight which viral targets are best to include in a vaccine and how this impacts the induced immune response and, ultimately, the safety and efficacy of a vaccine.
Since the outset of the COVID-19 pandemic, numerous risk factors for severe disease have been identified. Whether patients with rheumatic diseases, especially those receiving DMARDs, are at an increased risk of SARS-CoV-2 infection or severe COVID-19 disease remains unclear, although epidemiological studies are providing some insight.
The pathophysiology of coronavirus disease 19 (COVID-19) and diabetes mellitus are interlinked, and diabetes mellitus is associated with severe COVID-19 outcomes. This Review highlights new advances in diabetes mellitus and COVID-19, considering disease mechanisms and clinical management of patients with diabetes mellitus in the ongoing pandemic.
In this Review, Thiel and colleagues discuss the key aspects of coronavirus biology and their implications for SARS-CoV-2 infections as well as for treatment and prevention strategies.
In this Perspective, Su, Du and Jiang discuss lessons from previous vaccine development efforts for other viruses and how the mechanisms of vaccine-associated disease enhancement seen in some viral infections can inform the development of a safe and efficacious COVID-19 vaccine.
In this Review, Shi and colleagues summarize the exceptional amount of research that has characterized acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) since this virus has swept around the globe. They discuss what we know so far about the emergence and virology of SARS-CoV-2 and the pathogenesis and treatment of COVID-19.
Zitvogel and colleagues discuss the interplay between cancer and COVID-19 with respect to patient risk and prognosis, immune responses and potential therapies.