COVID-19

In this Review, Chan et al. explore major drug discovery approaches, preclinical antiviral evaluation models, virus-targeting and host-targeting therapeutic strategies, and key treatments currently used in clinical settings for COVID-19.

In this Review, Thiel and colleagues summarize our emerging knowledge of the SARS-CoV-2 intracellular life cycle and the molecular functions of the viral proteins, as well as their interaction with the host cell.

In this Review, Meyerowitz et al. examine the clinical presentations of COVID-19 in the era of widespread population immunity and explore current approaches to managing COVID-19 across different patient groups.

In this Review, Markov, Katzourakis and colleagues explore the evolution of SARS-CoV-2 at different scales, the phases of the COVID-19 pandemic, factors that drive the evolution of the virus, theories for the emergence of epidemiologically important variants and potential future evolutionary scenarios and their likely health repercussions.

In this Review, the authors summarize the mutations harboured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. They describe the impact of mutations on virus infectivity and transmissibility, and discuss SARS-CoV-2 evolution in the context of T cells, innate immunity and population immunity.

Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care.

In this Review, Minkoff and tenOever examine the relationship between SARS-CoV-2 biology and innate immunity, and they explore how antagonism and dysregulation of host innate immune defences contribute to COVID-19 disease severity.

A better understanding of the transmission of SARS-CoV-2 is essential to inform public health measures. In this Review, Puhach, Meyer and Eckerle explore insights into what influences SARS-CoV-2 shedding, how this drives transmission and the tools available to measure this and determine infectiousness.

The COVID-19 pandemic has had a considerable impact on respiratory virus infections worldwide. In this Review, Chu and colleagues discuss the changes in community spread and consequent infections by respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the course of the pandemic, and describe the impact on the evolution and genetic diversity of these viruses.

In this Review, Carabelli, Robertson and colleagues explore data on the neutralization of globally circulating variants of concern by monoclonal antibodies (mAbs) and discuss how knowledge of the dynamics of viral evasion of mAbs can contribute to viral surveillance and the development of novel mAb treatments, as well as inform predictions of resistance that may arise in the future.

In this Review, Lamers and Haagmans explore recent clinical and experimental advances in understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis, interactions with host cells and the involvement of the immune system in the development of severe disease. Specifically, they focus on mechanisms underlying the development of COVID-19-associated acute respiratory distress syndrome.

Bats harbour a multitude of coronaviruses and owing to their diversity and wide distribution are prime reservoir hosts of emerging viruses. Ruiz-Aravena, McKee and colleagues analyse the currently available information on bat coronaviruses and discuss their role in recent and potential future spillovers.

Global change, including climate change, urbanization and global travel and trade, has affected the emergence and spread of infectious diseases. In the Review, Baker, Metcalf and colleagues examine how global change affects infectious diseases, highlighting examples ranging from COVID-19 to Zika virus disease.

Elucidating the structure and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins is vital for understanding the molecular mechanisms of viral replication and COVID-19 pathogenesis, and could lead to the development of novel therapeutics. In this Review, Yang and Rao delineate the structural features of SARS-CoV-2 from the whole viral particle to the individual viral proteins and discuss their functions as well as their potential as targets for therapeutic interventions.

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.

In this Review, Schultz-Cherry, Thomas and colleagues discuss the pathogenesis of influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the human respiratory tract, the contribution of the host response to severe disease, epithelial repair mechanisms following infection, and current and potential future therapies for influenza virus and SARS-CoV-2 infections.

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.

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, Vandenberg et al. explore the crucial role of diagnostic tests during the first global wave of coronavirus disease 2019 (COVID-19) and the technical and implementation problems encountered during the early phase of the pandemic, and they define future directions for the progressive and better use of diagnostics during a possible resurgence of COVID-19 in future global waves or regional outbreaks.

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.

The COVID-19 pandemic has prompted unparalleled progress in the development of vaccines and therapeutics in many countries, but it has also highlighted the vulnerability of resource-limited countries in Africa. Margolin and colleagues review global efforts to develop SARS-CoV-2 diagnostics, therapeutics and vaccines, with a focus on the opportunities and challenges in Africa.

Bats harbour a large number of different viruses, some of which have spilled over to cause human disease. In this Review, Letko, Munster and colleagues discuss the diversity of bat viruses and the factors that determine the emergence of zoonotic viruses from bats.

Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.

Decades of coronavirus research and intense studies of SARS-CoV-2 since the beginning of the COVID-19 pandemic have led to an unprecedented level of knowledge of coronavirus biology and pathogenesis, yet many outstanding questions remain. Here, we discuss knowledge gaps and research priorities in the field.

Global COVID-19 vaccine equity remains aspirational for much of the world. But the emergence of rapidly evolving SARS-CoV-2 variants provides new opportunities to correct past public policies, support local vaccine production and combat rising anti-vaccine aggression.

The comparatively milder infections with the Omicron variant and higher levels of population immunity have raised hopes for a weakening of the pandemic. We argue that the lower severity of Omicron is a coincidence and that ongoing rapid antigenic evolution is likely to produce new variants that may escape immunity and be more severe.

The magnitude of immune evasion of Omicron raises the question whether it should be considered as a distinct SARS-CoV-2 serotype. Here, we discuss lines of evidence in support or against the concept of SARS-CoV-2 serotypes, and the implications of this classification.

This month’s Under the Lens discusses a few of the growing number of recent molecular simulation studies that have made substantial contributions towards our mechanistic understanding of the spike protein of SARS-CoV-2.

This Genome Watch highlights how the SARS-CoV-2 pandemic laid the groundwork for continued use of real-time genomic epidemiology for public health responses in low-and-middle-income countries.

The SARS-CoV-2 pandemic has seen a notable global reduction in influenza cases of both influenza A and B viruses. In particular, the B/Yamagata lineage has not been isolated from April 2020 to August 2021, suggesting that this influenza lineage may have become extinct, which may provide opportunities for improving availability and effectiveness of influenza vaccines.

In settings with limited resources and a wide range of possible etiologies, molecular technologies offer an effective solution for infectious disease diagnostics, because they are agile, fast and flexible. Health systems that routinely use molecular diagnostics will achieve economies of scale, maximize limited expertize and rapidly respond to new threats.

This month’s Genome Watch highlights how metagenomics could link the gut microbiota and COVID-19 disease outcomes and track emerging SARS-CoV-2 variants, with the potential to inform clinical practice and public health policy.

The integrative environment-health sciences including One Health, Conservation Medicine, EcoHealth and Planetary Health embody the transdisciplinary synthesis needed to understand the multitude of factors that underpin emerging infections and their management. Future successes in confronting and resolving the complex causal basis of disease emergence to generate robust, systems-oriented risk reduction strategies that preserve both human health as well as promoting sustainable futures represent the ‘Moon Shot’ for the integrative environment-health sciences.

Scientists around the world have risen to the challenges posed by COVID-19 by rapidly transforming their laboratories and refocusing their research efforts.

This month’s Genome Watch highlights how the search for the origins of SARS-CoV-2 emphasizes the need for integrated phylogenetic methods.

Scientists around the world have risen to the challenges posed by COVID-19 by rapidly transforming their laboratories and refocusing their research efforts. In the first of a new series of Feature articles to highlight these efforts, we interviewed three researchers at the Icahn School of Medicine at Mount Sinai.

This month’s Genome Watch highlights how genomic surveillance can provide important information for identifying and tracking emerging pathogens such as SARS-CoV-2.

Coronavirus disease 2019 may have a complex long-term impact on antimicrobial resistance (AMR). Coordinated strategies at the individual, health-care and policy levels are urgently required to inform necessary actions to reduce the potential longer-term impact on AMR and on access to effective antimicrobials.

This month’s Under the Lens discusses how structural studies of the SARS-CoV-2 spike glycoprotein might guide a path towards a vaccine.