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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.<\/jats:p>","DOI":"10.1136\/jitc-2020-000930","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T08:09:31Z","timestamp":1588925371000},"page":"e000930","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct04320615","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04315298","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04324021","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Fernanda I","family":"Arnaldez","sequence":"first","affiliation":[{"name":"MacroGenics Inc, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J","family":"O\"Day","sequence":"additional","affiliation":[{"name":"John Wayne Cancer Institute and Cancer Clinic, Providence Saint John\u2019s Health Center, Santa Monica, California, United States"},{"name":"Providence Los Angeles Metro Hospitals, Santa Monica, California, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G","family":"Drake","sequence":"additional","affiliation":[{"name":"Herbert Irving Cancer Center, Columbia University Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard A","family":"Fox","sequence":"additional","affiliation":[{"name":"Earle A Chiles Research Institute, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Fu","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J","family":"Urba","sequence":"additional","affiliation":[{"name":"Earle A Chiles Research Institute, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Montesarchio","sequence":"additional","affiliation":[{"name":"A.O.R.N. dei Colli Monaldi-Cotugno-CTO Hospitals, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S","family":"Weber","sequence":"additional","affiliation":[{"name":"Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Wei","sequence":"additional","affiliation":[{"name":"University of Science and Technology of China, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon M","family":"Wigginton","sequence":"additional","affiliation":[{"name":"Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo Antonio","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori IRCCS Fondazione \"G. 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