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Int Rev Immunol . Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality

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  • Int Rev Immunol . Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality


    Int Rev Immunol


    . 2021 Feb 22;1-14.
    doi: 10.1080/08830185.2021.1884248. Online ahead of print.
    Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality


    Yifan Que 1 , Chao Hu 2 , Kun Wan 3 , Peng Hu 1 , Runsheng Wang 1 , Jiang Luo 2 , Tianzhi Li 2 , Rongyu Ping 4 , Qinyong Hu 5 , Yu Sun 6 , Xudong Wu 7 , Lei Tu 8 , Yingzhen Du 1 , Christopher Chang 9 10 , Guogang Xu 2



    Affiliations

    Abstract

    The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1β and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.

    Keywords: COVID-19; IL-6; Kawasaki disease; NF-κB; SARS-CoV-2; cytokine release syndrome; hemophagocytic lymphohistiocytosis (HLH); multisystem inflammatory syndrome in children (MIS-C).

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