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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.
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.
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.
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.
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.
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.
It has been suggested that pangolin coronaviruses may be the origin of SARS-CoV-2. Here the authors show that the Pangolin-CoV spike is structurally closely related to the closed form of SARS-CoV-2 spike and exhibits similar binding properties to human and pangolin ACE2; although neither spike binds bat ACE2.
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 PaO2/FiO2 ratios and oxygen-support status. Relative to an external control group, bevacizumab shows clinical efficacy by improving oxygenation.
Several mRNA-based vaccines for SARS-CoV-2 are in late phase clinical development. Here, the authors show that a single immunization with a mRNA vaccine expressing SARS-CoV-2 spike RBD induces neutralizing antibodies that are maintained for at least 6.5 months and confer protection in a sera transfer study in mice.
Establishing the natural history of COVID-19 requires longitudinal data from population-based cohorts. Here, the authors use linked primary care, testing, and hospital data to describe the disease in ~100,000 individuals with a COVID-19 diagnosis among a population of ~5.5 million in Catalonia, Spain.
New analysis tracking the course of the COVID-19 epidemic in sub-Saharan Africa shows high country-to-country variation in disease and mortality burdens, as well as demonstrating a minimal role for climate in the spread of SARS-CoV-2 when compared with other factors, such as human mobility.
Interrogation of 1,365 near whole-genome sequences of SARS-CoV-2 variants isolated in South Africa during the first 6 months of the global pandemic reveals three major monophyletic lineages responsible for more than half of the infections in the country and underscores the value of integrating genomic surveillance methods to inform the national pandemic response.
Severe COVID-19 is characterized by hyperinflammation, and there is a need for accurate predictive biomarkers of progression. Lehuen et al. demonstrate that patients with severe COVID-19 show a dramatic loss of MAIT cells, and those that do remain are in a highly activated state.
BNT162b1 and BNT162b2 are two candidate mRNA vaccines against COVID-19 that elicit high virus-entry inhibition titres in mice, elicit high virus-neutralizing titres in rhesus macaques and protect macaques from SARS-CoV-2 challenge.
It is a challenging task for any research field to screen the literature and determine what needs to be included in a systematic review in a transparent way. A new open source machine learning framework called ASReview, which employs active learning and offers a range of machine learning models, can check the literature efficiently and systemically.
In drug discovery and repurposing, systematic analysis of genome-wide gene expression of chemical perturbations on human cell lines is a useful approach, but is limited due to a relatively low experimental throughput. Computational, deep learning methods can help. In this work a graph neural network called Deep Chemical Expression is developed that can predict chemical-induced gene expression profiles. It is applied to identify drug repurposing candidates for COVID-19 treatments.
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.
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.
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 (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.
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.
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.
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.
Unexpected direct and indirect risks of participating in clinical trials have emerged during COVID-19 that investigators and institutional review boards may not be sure how to investigate. How should existing guidance and ethical frameworks for clinical trials be applied in a pandemic setting?
Data on the efficacy and safety of SARS-CoV-2 vaccines are now available, but evidence for these vaccines in those who are immunocompromised (including patients with inflammatory bowel diseases) are lacking. As vaccination begins, questions on advantages and disadvantages can be partially addressed using the experience from other vaccines or immune-mediated inflammatory disorders.
As a physician scientist caring for older adults in New York City during the peak of the COVID-19 pandemic, I reflect on my experiences, the stark contrast in resource availability between hospitals and nursing homes, and the scientific opportunities and challenges for aging research.
COVID-19 models have been extensively used to inform public health officials about potential interventions. Nevertheless, careful attention must be taken when extrapolating projections and parameters across different regions, as there is no one-size-fits-all model for the pandemic.
Detailed, accurate data related to a disease outbreak enable informed public health decision making. Given the variety of data types available across different regions, global data curation and standardization efforts are essential to guarantee rapid data integration and dissemination in times of a pandemic.
Stakeholders in public health must lobby policy makers to make decisions based on evidence, not political expediency, particularly when the studies that hang in the balance are critical to understanding the origins of epidemics.
The pandemic has thrust many mainstream journalists into unfamiliar grounds, including coverage of expert opinion that is not backed up by peer-reviewed content, reporting on preprints, and assessing high-complexity instant-response science. How did they manage? We asked five journalists from mainstream media about their experience.
The prevalence of COVID-19-associated diabetes is not the result of a single event but of a combination of disease susceptibility associated with chronic illness and COVID-19-specific mechanisms affecting metabolism. Whether a separate entity of post-COVID-19 diabetes, possibly associated with lasting β-cell damage, also exists is not yet clear.
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.
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.
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.