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.
【저자키워드】 COVID-19, Inflammation, Cytokine storm, Mortality, IL-6, immunopathology, chemokine, IL-1, 【초록키워드】 Treatment, SARS-CoV-2, Coronavirus disease 2019, Efficacy, coronavirus, clinical trial, Infection, Interpretation, Therapeutic strategies, death, pathway, morbidity and mortality, targets, Critical, clinical feature, COVID-19 patients, Combination, Clinical efficacy, Inflammatory, COVID-19 mortality, COVID-19 patient, IL-6 blockade, acute respiratory syndrome, Factor, Stage, blockade, Prevent, inflammatory mediator, hyperinflammatory cytokine storm, can be used, notable, immunopathological, ill patients, 【제목키워드】 target, Preventing,