Coronavirus

Multivalent nanobodies against SARS-CoV-2 from mice engineered to produce camelid nanobodies recognize conserved epitopes that are inaccessible to human antibodies and show promise as a strategy for dealing with viral escape mutations.

Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

Here the authors use RT-qPCR and mass spectrometry to analyze longitudinal blood samples from intensive care unit (ICU) COVID-19 patients and controls. They find that viral RNA and pentraxin-3 predict 28-day ICU mortality and that galectin-3-binding protein is an interaction partner of SARS-CoV-2 spike glycoprotein with antiviral properties.

An engineered IgM antibody administered intranasally in mice shows high prophylactic efficacy and therapeutic efficacy against SARS-CoV-2, and is also effective against multiple variants of concern that are resistant to IgG-based therapeutics.

A sustainable and biodegradable antiviral filtration membrane composed of amyloid nanofibrils made from food-grade milk proteins and iron oxyhydroxide nanoparticles can be used to trap a number of enveloped and non-enveloped viruses in water.

Here, the authors perform repurposing screens of the ReFRAME drug library in two cell lines and identify inhibitors of SARS-CoV-2 infection. Antiviral activity of prodrug MK-4482 is confirmed in hamsters.

Non-pharmaceutical interventions (NPIs) implemented to interrupt COVID-19 transmission may also impact the spread of other infectious diseases. Here, the authors estimate that influenza activity in China and the United States reduced by up to 80% when NPIs were in place in the 2019–2020 season.

The urgency of the developing COVID-19 epidemic has led to a large number of novel diagnostic approaches, many of which use machine learning. DeGrave and colleagues use explainable AI techniques to analyse a selection of these approaches and find that the methods frequently learn to identify features unrelated to the actual disease.

There are currently no drugs available to treat SARS-CoV-2 infection. A promising alternative treatment for COVID-19 patients is convalescent plasma. Here, Gharbharan et al. collect covalescent plasma and report no overall clinical benefit for 86 patients hospitalized for COVID-19 and treated with 300 mL convalescent plasma.

Analysis of circulating SARS-CoV-2 viruses during the first and second waves of COVID-19 in Amazonas, Brazil, shows successive lineage replacements led to predominance of the variant of concern P.1 and are associated with variable levels of social distancing.

Fiorina and colleagues document alterations in glucose metabolism in patients with COVID-19 and use continuous glucose monitoring to show that glycaemic abnormalities could still be detected 2 months after disease onset in patients who had recovered.

Here, the authors characterize the antibody response from vaccinated (Pfizer BNT-162b2), infected and uninfected individuals against emerging variants of concern of SARS-CoV-2, finding reduced neutralization of a South African isolate. High IgG titers in the saliva of vaccinees suggest that transmission may be reduced.

SARS-CoV-2 infection induces long-lived bone marrow plasma cells that correlate with anti-SARS-CoV-2 spike protein antibody titres in individuals who have recovered from COVID-19.

Perturbed T cell responses and disturbed cytokine secretion have been shown during SARS-CoV2 infection in patients. Here the authors show reduced polyclonal T cell activity in COVID-19 patients that is caused by plasma factors and linked to poor prognosis and viral persistence.

A study of hospitalized patients infected with SARS-CoV-2 and who have liquid or solid cancer suggests that hematologic malignancy is an independent risk factor for mortality and that CD8⁺ T cells might limit infection in this setting irrespective of humoral immunity.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

Pre-existing immune responses between antigenically related viruses can influence responses in viral infections or vaccinations. Here the authors assess and characterize the presence of antibody and memory B cell populations specific to SARS-CoV2 and endemic human coronaviruses.

An analysis of COVID-19 vaccine allocation frameworks in the United States across 64 Centers for Disease Control and Prevention jurisdictions reveals that, as of 31 March 2021, 37 jurisdictions had adopted disadvantage indices to reduce health disparities. The analysis also highlights the importance of vaccine prioritization based on health and place.

Safety and immunogenicity results in humans of a two-dose SARS-CoV-2 vaccine made from plants support further assessment of potential efficacy.

Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

Heterologous vaccination regimens for COVID-19 could be useful for example if there is a shortage of one vaccine type. Here, Spencer et al. show that heterologous vaccination with a self-amplifying RNA vaccine and an adenoviral vectored vaccine performs at least as well as the homologous vaccinations in mice.

SARS-CoV-2 orf9b binds to the mitochondrial outer membrane protein TOM70 and has been linked to the suppression of interferon responses. Here, the authors characterize the interactions of SARS-CoV-2 orf9b and human TOM70 biochemically, and they determine the 2.2 Å crystal structure of the TOM70 cytosolic domain with a bound SARS-CoV-2 orf9b peptide.

The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.

RNA sequencing, ribosome profiling and metabolic labelling of newly synthesized RNA reveal the strategy used by SARS-CoV-2 to shut off cellular protein synthesis in the host and allow the translation of viral transcripts.

Statistical analysis of COVID-19 transmission among users of a smartphone-based digital contact-tracing app suggests that such apps can be an effective measure for reducing disease spread.

Estimates of COVID-19-related mortality are limited by incomplete testing. Here, the authors perform counterfactual analyses and estimate that there were 59,000–62,000 deaths from COVID-19 in Italy until 9^th September 2020, approximately 1.5 times higher than official statistics.

RIG-I is a cytosolic nucleic acid sensor triggering type I IFN production. Takaoka and colleagues find that RIG-I recognizes SARS-CoV-2 RNA in a noncanonical manner and fails to activate type I IFN, but it directly restricts viral replication.

Antibodies against SARS-CoV-2 S protein can provide a treatment strategy for COVID-19. Here, Guo et al. provide the crystal structure of a SARS-CoV2 neutralizing antibody isolated from a convalescent patient and highlight the therapeutic efficacy in a rhesus monkey model of an engineered version with optimized pharmacokinetic and safety profile.

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.

While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.

Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.

The rise of more-transmissible viral mutants demands new ways to prevent, detect, track and treat SARS-CoV-2 infections.

Focusing only on cases and deaths hides the pandemic’s lasting health burden on people, societies and economies.

Wealthier countries must join the United States, Russia and China in recognizing that everyone benefits if vaccine manufacturing is distributed evenly around the world.

It could take years to reveal the true impact of closed borders, cancelled travel plans and vaccine delays.

Researchers have spoken out against policies that have exacerbated the country’s coronavirus crisis. Policymakers must listen.

This Comment discusses how the emerging SARS-CoV-2 variants of concern could impact on the hopes of long-term pandemic control through vaccination and the mutations that might be relevant to the design of modified vaccines.

In this article, Niemi, Daly and Ganna discuss how large-scale genomics studies are providing a rapidly maturing understanding of the influence of host genetics on coronavirus disease 2019 (COVID-19) susceptibility and severity. They also describe the implications for identifying causal mechanisms of pathology and potential therapeutic opportunities.

In this Review, the authors describe how phylogenetic and phylodynamic methods provide insight into viral evolution, focusing on the SARS-CoV-2 pandemic. The approaches reveal routes and timings of transmission events, and they can assess the effectiveness of various intervention measures aimed at controlling the virus.

In this Review, the authors describe our latest understanding of the emergence and properties of SARS-CoV-2 genetic variants, particularly those designated as WHO (World Health Organization) ‘variants of concern’. They focus on the consequences of these variants for antibody-mediated virus neutralization, with important implications for reinfection risk and for vaccine effectiveness.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

Population-scale testing is an essential component of responses to the COVID-19 pandemic and is likely to become increasingly important in public health. Here, Mercer and Salit describe the roles of testing during the COVID-19 pandemic, including in genomic surveillance, contact tracing and environmental testing.

A review of COVID-19 responses in 28 selected countries identifies elements of highly effective public health responses and offers recommendations toward strengthening health systems resilience.

Immune-related disorders in patients with COVID-19 are increasingly being reported worldwide, with thousands of cases recorded of manifestations that can mimic a broad range of systemic and organ-specific inflammatory and autoimmune diseases.

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.

Infectious diseases are an ever-present global threat. In this Review, Kwok, Mentzer and Knight discuss our latest understanding of how human genetics influence susceptibility to disease. Furthermore, they discuss emerging progress in the interplay between host and pathogen genetics, molecular responses to infection and vaccination, and opportunities to bring these aspects together for rapid responses to emerging diseases such as COVID-19.