{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:36:49Z","timestamp":1790311009131,"version":"4.1.0"},"posted":{"date-parts":[[2023,6,6]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":15,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The systemic inflammatory response seen in patients with severe COVID-19 shares many similarities with the changes observed in hemophagocytic lymphohistiocytosis (HLH); a disease characterized by excessive immune activation. Many patients with severe COVID qualify for a diagnosis of HLH. Etoposide, an inhibitor of topoisomerase II is used to control inflammation in HLH. This randomized, open-label, single center phase II trial attempted to determine whether etoposide can be used to blunt the inflammatory response in severe COVID. This trial was closed early after eight patients were randomized. This underpowered trial did not meet its primary endpoint of improvement in pulmonary status by two categories on an 8 point ordinal scale of respiratory function. There were not significant differences in secondary outcomes including overall survival at 30 days, cumulative incidence of grade 2 through 4 adverse events during hospitalization, duration of hospitalization, duration of ventilation and improvement in oxygenation or paO2\/FIO2 ratio or improvement in inflammatory markers associated with cytokine storm. A high rate of grade 3 myelosuppression was noted in this critically ill population despite dose reduction, a toxicity which will limit future attempts to explore the utility of etoposide for virally-driven cytokine storm or HLH.<\/jats:p>","DOI":"10.1101\/2023.06.05.23290969","type":"posted-content","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T17:12:06Z","timestamp":1686071526000},"source":"Crossref","is-referenced-by-count":1,"title":["A prospective, single-center, randomized phase 2 trial of etoposide in severe COVID-19"],"prefix":"10.64898","author":[{"given":"Meredith","family":"Halpin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Lerner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Sagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Govender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavesh","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Weinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayna","family":"Sarosiek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-4528","authenticated-orcid":false,"given":"J. Mark","family":"Sloan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023060921000577000_2023.06.05.23290969v1.1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13102"},{"key":"2023060921000577000_2023.06.05.23290969v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116846"},{"key":"2023060921000577000_2023.06.05.23290969v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68232-9"},{"key":"2023060921000577000_2023.06.05.23290969v1.4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0172"},{"key":"2023060921000577000_2023.06.05.23290969v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"2023060921000577000_2023.06.05.23290969v1.6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302282"},{"key":"2023060921000577000_2023.06.05.23290969v1.7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12916-020-01682-y","article-title":"Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases?","volume":"18","year":"2020","journal-title":"BMC Med"},{"key":"2023060921000577000_2023.06.05.23290969v1.8","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1016\/j.chest.2020.09.077","article-title":"Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019","volume":"159","year":"2021","journal-title":"Chest"},{"key":"2023060921000577000_2023.06.05.23290969v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/AJCP\/AQAA124"},{"key":"2023060921000577000_2023.06.05.23290969v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436"},{"key":"2023060921000577000_2023.06.05.23290969v1.11","doi-asserted-by":"crossref","unstructured":"REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, E.C. , Bradbury, C.A. , McVerry, B.J. ,et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med 385, 777\u2013789. https:\/\/doi.org\/10.1056\/NEJMoa2103417","DOI":"10.1056\/NEJMoa2103417"},{"key":"2023060921000577000_2023.06.05.23290969v1.12","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.6775"},{"key":"2023060921000577000_2023.06.05.23290969v1.13","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1056\/NEJMoa2028700","article-title":"Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia","volume":"384","year":"2021","journal-title":"New England Journal of Medicine"},{"key":"2023060921000577000_2023.06.05.23290969v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-05991-x"},{"key":"2023060921000577000_2023.06.05.23290969v1.15","unstructured":"Staff, F.J.F.G., April 8, 2020, nside Boston Medical Center: The heart of the coronavirus storm - The Boston Globe [WWW Document]. BostonGlobe.com. URL https:\/\/www.bostonglobe.com\/2020\/04\/18\/metro\/inside-boston-medical-center-heart-coronavirus-storm\/ (accessed 4.10.23)."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.06.05.23290969","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:35:01Z","timestamp":1768505701000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.06.05.23290969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,6]]},"references-count":15,"URL":"https:\/\/doi.org\/10.1101\/2023.06.05.23290969","relation":{},"subject":[],"published":{"date-parts":[[2023,6,6]]},"subtype":"preprint"}}