The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Highlights • In December 2019, a novel coronavirus of SARS-CoV-2hit Wuhan, Hubei, China, and then spread globally. • SARS-CoV-2 generally causes a mild lower respiratory infection in humans, however, in some severe cases, multiple organ dysfunction occurs. • Overproduction of cytokines, termed cytokine storm, may involve in disease progression and even be responsible for deaths. • Application of immune-modulators might become a complement to support treatment and flip on the light switch for severe patients.
【저자키워드】 Cytokine storm, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ACE2, angiotensin-converting enzyme 2, Coronavirus disease 2019 (COVID-19), Inflammatory cytokines, JAK, Janus kinase, ARDS, acute respiratory distress syndrome, IL, interleukin, MCP, monocyte chemoattractant protein, SARS, Severe acute respiratory syndrome, MERS, Middle East respiratory syndrome, WHO, World Health Organization, CRP, C-reactive protein, CNS, Central Nervous System, CoV, coronavirus, TNF, Tumor Necrosis Factor, IFN, Interferons, PRRs, Pattern Recognition Receptors, DC, dendritic cell, PBMC, peripheral blood mononuclear cell, CCL, chemokine ligand, PAMPs, pathogen-associated molecular patterns, ALI, Acute Lung Injury, NLR, neutrophil-to-lymphocyte ratio, CXCL, Chemokine (C-X-C motif) ligand, GMCSF, Granulocyte-macrophage colony-stimulating factor, STAT, Signal transducer and activator of transcription, Multiple organ dysfunctions, IL-1RA, IL-1 receptor antagonist, IP-10, IFN-γ-inducible protein-10, Th, helper T cell, NK, natural killer cell, B, B lymphocyte, Th2, T-helper-2 cell, BMSC, bone marrow stromal cell, Th1, T-helper-1 cell, GCSF, granulocyte colony stimulating factor, FGF, fibroblast growth factor, PDGF, platelet derived growth factor, VEGF, vascular endothelial cell growth factor, MIP1A, macrophage Inflammatory Protein 1 Alpha, MIP1B, macrophage Inflammatory Protein 1 beta, TLRs, Toll-like receptors, COVID-CSS, COVID-19 related cytokine storm syndrome, NF-κB, nuclear factor κB, IRF3, IFN regulatory factor-3,