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In this Collection, we bring you articles that highlight the latest research and insight into the immunology of SARS-CoV-2 and the associated disease COVID-19. They cover our emerging understanding of the immune response to this new coronavirus, prospects for vaccine development, immunopathology of COVID-19 and how it might be treated with immunomodulatory drugs.
You can also read the latest news and opinion from Nature on the novel coronavirus and COVID-19 here, and research papers from across the Nature journals here.
In this Perspective, Lok-Yin Roy Wong and Stanley Perlman consider how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related coronaviruses are able to drive immune dysregulation and immunopathology. They provide an overview of the coronavirus-derived molecules that interfere with key innate immune responses, including interferon pathways and complement, NF-κB signalling and inflammasome activation, as well as with the activation of host adaptive immunity.
Individuals with asymptomatic COVID-19 can transmit the virus and may be at risk of long-term disease. In this Progress article, Boyton and Altman present current insights into immune responses in asymptomatic SARS-CoV-2 infection and discuss the relevance of asymptomatic disease for public health strategies.
This Progress article provides an update on the COVID-19 vaccine effort in the light of ongoing vaccine efficacy studies and real-world data on vaccine effectiveness, including the impact of virus variants of concern and challenges for global deployment.
This Progress article brings us up to date on the role of inflammasomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19, describing how they may be activated during infection and contribute to the overexuberant inflammatory response in severe disease, and the efforts being taken to target them therapeutically.
This Progress article summarizes our current understanding of the immune mechanisms of protection induced by the available COVID-19 vaccines. The authors compare vaccine-induced antibody responses following one or two doses of different vaccines and consider the relative importance of neutralizing antibodies for vaccine-mediated protection against SARS-CoV-2.
Emerging diseases that affect humans often arise due to the crossover of infectious agents from animal reservoirs. In this Perspective, George Warimwe and colleagues discuss the concept of ‘One Health vaccinology’, an approach that aims to use key lessons from human and veterinary immunology to develop more effective vaccination strategies for emerging infectious diseases.
The duration of immunity to coronavirus disease 2019 (COVID-19) from prior infection and longer-term risk of reinfection are currently unclear. Cromer and colleagues discuss the immune control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the implications of this for the future control of the pandemic.
Peter Taylor and colleagues provide an overview of the neutralizing monoclonal antibody therapies that have been developed to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discuss the clinical utility of these antibodies.
Here, the authors propose that SARS-CoV-2 induces a prothrombotic state, with dysregulated immunothrombosis in lung microvessels and endothelial injury, which drive the clinical manifestations of severe COVID-19. They discuss potential antithrombotic and immunomodulating drugs that are being considered in the treatment of patients with COVID-19.
In this Perspective, Cobey, Larremore, Grad and Lipsitch argue that dose-sparing regimens of COVID-19 vaccines can reduce disease incidence, prevalence and burden and explain why they think that such strategies would also slow the rate of viral escape from vaccine or naturally induced immunity.
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, aimed at a broad scientific audience, provides an introductory guide to the history, development and immunological basis of vaccines, immunization and related issues to provide insight into the challenges facing immunologists who are designing the next generation of vaccines.
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.
In this Perspective, Alon and colleagues discuss how insights into immune cell trafficking during pneumotropic influenza virus infections may inform our understanding of immune cell recruitment to the respiratory tract in patients with coronavirus disease 2019 (COVID-19). Moreover, they examine the emerging knowledge of vascular pathologies beyond the lung caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Are you new to virus research and trying to interpret the ever-expanding literature on immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? Here, the authors compare the different assays and animal models used to measure immunity to SARS-CoV-2 infection and reconcile differences in apparent potency of antibodies assessed in different assays.
How does the discovery of SARS-CoV-2 cross-reactive T cells in unexposed individuals change our understanding of the COVID-19 pandemic? In this Perspective, the authors provide a thought experiment to explain why the discovery of cross-reactive T cells may affect disease severity in individuals, but is unlikely to change our estimate of the herd immunity threshold.
This Review outlines the guiding immunological principles for the design of coronavirus disease 2019 (COVID-19) vaccine strategies and analyses the current COVID-19 vaccine landscape and the challenges ahead.
Antibody-dependent enhancement (ADE) has been described as a mechanism that contributes to the pathogenesis of dengue virus infection. Limited evidence also suggests that it can also occur in other viral infections. Here, the authors explore the history of the ADE phenomenon, discuss the diversity of Fc effector functions and consider its potential relevance in the context of SARS-CoV-2 infection.
In this Progress article, Zeyu Chen and E. John Wherry summarize early reports of the T cell responses observed in patients with COVID-19, emphasizing how different immune response characteristics in different patients may reflect a spectrum of disease phenotypes.
Recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) as well as antibodies targeted at GM-CSF or its receptor are being tested in clinical trials for coronavirus disease 2019 (COVID-19). This Perspective introduces the pleiotropic functions of GM-CSF and explores the rationale behind these different approaches.
This Progress article from Merad and Martin examines our current understanding of the excessive inflammatory responses seen in patients with severe COVID-19. The authors focus on the emerging pathological roles of monocytes and macrophages and discuss the inflammatory pathways that are currently being targeted in the clinic.
In the short time since SARS-CoV-2 infections emerged in humans, much has been learned about the immunological processes that underlie the clinical manifestation of COVID-19. Here, the authors provide an overview of the pathophysiology of SARS-CoV-2 infection and discuss potential therapeutic approaches.
Here a group of leaders in the field define our current understanding of ‘trained immunity’, which refers to the memory-type responses that occur in the innate immune system. The authors discuss our current understanding of the key epigenetic and metabolic processes involved in trained immunity and consider its relevance in immune-mediated diseases and cancer.
Here, John Kelton and colleagues provide an overview of vaccine-induced immune thrombotic thrombocytopenia (VITT), a very rare complication that has been observed following vaccination with adenoviral vector-based COVID-19 vaccines.
Muhammad Suleman Rana and colleagues from the National Institute of Health in Pakistan discuss the urgent need to implement catch-up vaccination programmes for measles and polio to prevent resurgence of these deadly diseases.
This Comment article proposes that T cell-oriented vaccine strategies should be considered to control the COVID-19 pandemic in the longer term, given declining levels of neutralizing antibodies with time after vaccination or infection and the emergence of viral escape variants.
It took roughly 1 year for a COVID-19 vaccine to become available, yet, four decades after the first patient with HIV was described, we do not yet have a vaccine for HIV. Here, Barton Haynes examines the biological reasons why vaccine development for HIV is so exceptionally challenging.
In this Comment article, Sofonias Tessema and John Nkengasong provide an overview of the current state of the COVID-19 pandemic in Africa and the challenges posed by the triple burden of emerging, endemic and non-communicable diseases.
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.
The identification of elevated IL-6 levels in patients with severe COVID-19 led to the rapid development of clinical trials targeting this cytokine. Overall, these trials do not support the widespread use of IL-6 antagonists in hospitalized patients with mild-to-moderate disease, but IL-6 antagonists may be beneficial when rapidly deployed in patients with severe COVID-19, as we discuss here.
This Comment outlines how the recently licensed vaccines for COVID-19 activate innate immune mechanisms to promote immune memory to SARS-CoV-2. The authors also consider future challenges that could limit vaccine efficacy.
Reassuring data from accidental pregnancies that have occurred in the clinical trials of approved COVID-19 vaccines indicate that vaccination does not harm fertility or increase the rate of miscarriage.
Neurological symptoms are increasingly being observed in patients with COVID-19; this Comment article considers whether cross-reactive antibodies might contribute to the pathology associated with SARS-CoV-2 infection.
This Web Watch introduces the VaC tracker, a web resource that features an overview of the COVID-19 ‘vaccine landscape’, a clinical trials database and a ‘living review’ that distils the results of vaccine trials as they become available.
For this Viewpoint, Nature Reviews Immunology asked the presidents of 16 immunology societies from around the world to discuss how their society and its members responded to the COVID-19 pandemic. Their answers highlight the incredible contributions that immunologists around the globe have made following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
During the current COVID-19 pandemic, the concept of herd immunity has become a topic of much debate. This Comment examines the factors that determine it, discusses how far we have come and considers what it will take to reach herd immunity safely.
In this Comment, Jeong Seok Lee and Eui-Cheol Shin discuss contradictory results regarding the downregulation or upregulation of type I interferon responses in patients with COVID-19 and the implications for therapies that target this pathway.
The corticosteroid dexamethasome has been shown to reduce mortality in patients hospitalized with COVID-19 who require mechanical ventilation. Here, the authors describe how this immunosuppressive drug might work.
In this Comment article, Becker and colleagues consider how the excessive release of reactive oxygen species by neutrophils may perpetuate red blood cell dysfunction, thrombosis and tissue damage in severe cases of COVID-19.
Recent studies have shown T cell reactivity to SARS-CoV-2 in 20–50% of unexposed individuals; it is speculated that this is due to T cell memory to common cold coronaviruses. Here, Crotty and Sette discuss the potential implications of these findings for disease severity, herd immunity and vaccine development.
Why do some young and previously healthy individuals develop severe COVID-19? In this Comment, Casanova and colleagues suggest that monogenic inborn errors of immunity may be responsible based on lessons from other viral infections.
In this Comment, Anne Rowley discusses what we know so far about the recently described multisystem inflammatory syndrome in older children associated with SARS-CoV-2 infection and how it differs from Kawasaki disease.
Beyond neutralization, antibodies have immune-modulating functions that can be protective but, in some cases, can enhance pathology. Understanding these functions is critical for the development of safe vaccines and antibody therapies for COVID-19.
In this Comment, Greg Lemke and Gregg Silverman propose that the excessive blood clotting and immune activation seen in severe COVID-19 may be mechanistically linked through protein S, a ligand for the immunosuppressive TAM receptor family.
In this Viewpoint article, members of the Optimmunize consortium discuss the evidence for non-specific and sex-differential effects of vaccines and how this information might inform vaccine design and policy, including in relation to the COVID-19 pandemic.
Levels of the cytokine IL-17 positively correlate with disease severity in COVID-19. Here, the authors argue that existing anti-IL-17 therapies should be considered for the treatment of severe COVID-19.
This Comment article from the Precision Immunology Institute at the Icahn School of Medicine (PrIISM), New York, describes their efforts to provide critical reviews of COVID-19 articles posted daily on the preprint servers bioRxiv and medRxiv.
Immune-mediated inflammatory diseases are often treated with cytokine blocking therapy. This comment discusses whether such therapies may pose a risk — or even a benefit — in the context of the current COVID-19 pandemic.
In the short time since SARS-CoV2 emerged, much has been learned about the immunopathology of the infection. Here, Xuetao Cao discusses what these early insights imply for drug discovery and clinical management.