{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:20:49Z","timestamp":1772644849640,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,2]]},"group-title":"Epidemiology","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Interleukin-6 (IL-6) is a cytokine that plays a key role in systemic hyperinflammation and may mediate the relationship between acute COVID-19 and severe long-term outcomes such as Long COVID or death. IL-6 modulating drugs may reduce patients\u2019 risk of severe post-COVID-19 outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted an emulated target trial in a retrospective cohort of patients with moderate-to-severe rheumatoid arthritis who were prescribed IL-6 receptor antagonists (sarilumab or tocilizumab, pooled treatment) or other biologic agents (anakinra or baricitinib, pooled comparator) in 2022. We compared the 12\u2013month cumulative incidence of mortality and Long COVID (diagnosed and probable) between groups using Super Learner and targeted maximum likelihood estimation, adjusting for covariates of interest.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In our cohort of 3,553 patients, we found that prescription of IL-6 receptor antagonists was associated with a lower 12-month cumulative mortality (adjusted relative risk (aRR) 0.40, 95% CI 0.27, 0.59), diagnosed Long COVID aRR 0.42, 95% CI 0.23, 0.78), and probable Long COVID (aRR 0.71, 95% CI 0.61, 0.83), compared to prescription of other biologic agents, among rheumatoid arthritis patients.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IL-6 receptor antagonists may prevent the incidence of severe post-COVID-19 outcomes, such as Long COVID or mortality. This supports the hypothesis that IL-6 may be a mechanistic biomarker of COVID-19 sequelae and that acute COVID-19 severity may mediate this relationship.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.27.26347274","type":"posted-content","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T15:00:21Z","timestamp":1772463621000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-6 Receptor Antagonists and Severe Post-COVID-19 Outcomes: An Emulated Target Trial"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-0008","authenticated-orcid":false,"given":"Zachary","family":"Butzin-Dozier","sequence":"first","affiliation":[{"name":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manav","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunwen","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin-Chiun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Jerrod","family":"Anzalone","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha, NE, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-7754","authenticated-orcid":false,"given":"Eric","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rena C.","family":"Patel","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Wong","sequence":"additional","affiliation":[{"name":"Renaissance School of Medicine, Stony Brook University, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-2080","authenticated-orcid":false,"given":"Carolyn","family":"Bramante","sequence":"additional","affiliation":[{"name":"University of Minnesota, Minneapolis, MN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Sines","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026030405402153000_2026.02.27.26347274v1.1","doi-asserted-by":"crossref","unstructured":"Low, R. 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