The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

• Published in: Journal for immunotherapy of cancer 2020-05, Vol.8 (1), p.e000930
• Main Authors: Arnaldez, Fernanda I, O'Day, Steven J, Drake, Charles G, Fox, Bernard A, Fu, Bingqing, Urba, Walter J, Montesarchio, Vincenzo, Weber, Jeffrey S, Wei, Haiming, Wigginton, Jon M, Ascierto, Paolo Antonio
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Cancer; Coronavirus Infections - complications; Coronavirus Infections - drug therapy; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronaviruses; COVID-19; Cytokine Release Syndrome - complications; Cytokine Release Syndrome - drug therapy; Cytokine Release Syndrome - immunology; Cytokine Release Syndrome - pathology; Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Humans; Immunotherapy; Inflammation - complications; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Interferon-gamma - antagonists & inhibitors; Interleukin-1 - antagonists & inhibitors; Interleukin-17 - antagonists & inhibitors; Interleukin-23 - antagonists & inhibitors; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - genetics; Interleukin-6 - immunology; Interleukin-6 - metabolism; Janus Kinases - antagonists & inhibitors; Neoplasms - immunology; Neoplasms - therapy; Pandemics; Pneumonia, Viral - complications; Pneumonia, Viral - drug therapy; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Position and Guidelines; Respiratory diseases; Respiratory Distress Syndrome - complications; Respiratory Distress Syndrome - drug therapy; Respiratory Distress Syndrome - immunology; Respiratory Distress Syndrome - pathology; Severe Acute Respiratory Syndrome - pathology; Signal Transduction - drug effects; Societies, Medical; STAT Transcription Factors - antagonists & inhibitors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Ventilators
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-000930

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.