ABSTRACT
A unique feature of the cytokine storm in coronavirus disease 2019 (COVID-19) is the dramatic elevation of interleukin 10 (IL-10). This was thought to be a negative feedback mechanism to suppress inflammation. However, several lines of clinical evidence suggest that dramatic early proinflammatory IL-10 elevation may play a pathological role in COVID-19 severity.
Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Interleukin-10/immunology , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/virology , Cytokine Release Syndrome/metabolism , Epidemics , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-10/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , Models, Immunological , SARS-CoV-2/physiology , Severity of Illness IndexABSTRACT
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients' outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.
Subject(s)
Antibodies, Viral/biosynthesis , COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/therapeutic use , Asymptomatic Infections , COVID-19/prevention & control , COVID-19 Vaccines/isolation & purification , China , Drug Development/trends , Host Microbial Interactions/immunology , Humans , Immunity, Humoral , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Models, Immunological , Pandemics , Reinfection/immunology , Reinfection/prevention & control , Seroconversion , COVID-19 SerotherapyABSTRACT
Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.