Immunopathogenesis and treatment of cytokine storm in COVID-19

• Published in: Theranostics Vol. 11; no. 1; pp. 316 - 329
• Main Authors: Kim, Jae Seok, Lee, Jun Young, Yang, Jae Won, Lee, Keum Hwa, Effenberger, Maria, Szpirt, Wladimir, Kronbichler, Andreas, Shin, Jae Il
• Format: Journal Article Book Review
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2021; Ivyspring International Publisher
• Subjects: Adaptive immunity; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Autoimmune diseases; Azetidines - pharmacology; Azetidines - therapeutic use; Clinical Trials as Topic; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - immunology; COVID-19 - virology; COVID-19 Drug Treatment; Cytokine Release Syndrome - drug therapy; Cytokine Release Syndrome - immunology; Cytokine storm; Cytokines - antagonists & inhibitors; Cytokines - immunology; Cytokines - metabolism; Disease; Humans; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Infections; Inflammation; Interleukin 1 Receptor Antagonist Protein - pharmacology; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Janus Kinases - antagonists & inhibitors; Janus Kinases - metabolism; Lymphocytes; Mortality; Proteins; Purines - pharmacology; Purines - therapeutic use; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Review; SARS-CoV-2 - immunology; Sepsis; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Signal Transduction - drug effects; Signal Transduction - immunology; STAT Transcription Factors - antagonists & inhibitors; STAT Transcription Factors - metabolism; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; Treatment Outcome; Tumor necrosis factor-TNF; Viral infections; COVID-19; cytokine blockades; Coronavirus; cytokine storm; plasma exchange
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.49713

Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.