ArticlemedRxiv : the preprint server for health sciences2026
IL-6 Receptor Antagonists and Severe Post-COVID-19 Outcomes: An Emulated Target Trial.
Zachary Butzin-Dozier, Manav Kumar, Yunwen Ji, Lin-Chiun Wang, A Jerrod Anzalone, Eric Hurwitz, Rena C Patel, Rachel Wong, Carolyn Bramante, Benjamin Sines
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
10 authors.
Manav KumarSchool of Public Health, University of California, Berkeley, Berkeley, CA USA.
Yunwen JiSchool of Public Health, University of California, Berkeley, Berkeley, CA USA.
Lin-Chiun WangSchool of Public Health, University of California, Berkeley, Berkeley, CA USA.
A Jerrod AnzaloneUniversity of Nebraska Medical Center, Omaha, NE, USA.
Rena C PatelUniversity of Alabama at Birmingham, Birmingham, AL, USA.
Rachel WongRenaissance School of Medicine, Stony Brook University, New York, NY, USA.
Benjamin SinesUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Funding
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MUCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MClinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1MProject-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MPhenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4MTransform Dissemination and Implementation Science in CTSA ProgramsUL1TR002319 · NCATS · UNIVERSITY OF WASHINGTON · PI John K. Amory · 2017 to 2026
$100.0MClinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MWU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8MThe Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0MImplementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1MUC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3MBill & Melinda Gates Foundation INV-018455NCATS NIH HHS U24 TR002306NCATS NIH HHS UL1 TR001409NCATS NIH HHS UL1 TR001412NCATS NIH HHS UL1 TR001414NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001422NCATS NIH HHS UL1 TR001425NCATS NIH HHS UL1 TR001427NCATS NIH HHS UL1 TR001430NCATS NIH HHS UL1 TR001433NCATS NIH HHS UL1 TR001436NCATS NIH HHS UL1 TR001439NCATS NIH HHS UL1 TR001442NCATS NIH HHS UL1 TR001445NCATS NIH HHS UL1 TR001449NCATS NIH HHS UL1 TR001450NCATS NIH HHS UL1 TR001453NCATS NIH HHS UL1 TR001855NCATS NIH HHS UL1 TR001860NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR001866NCATS NIH HHS UL1 TR001872NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR001876NCATS NIH HHS UL1 TR001878NCATS NIH HHS UL1 TR001881NCATS NIH HHS UL1 TR001998NCATS NIH HHS UL1 TR002001NCATS NIH HHS UL1 TR002003NCATS NIH HHS UL1 TR002014NCATS NIH HHS UL1 TR002240NCATS NIH HHS UL1 TR002243NCATS NIH HHS UL1 TR002319NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002366NCATS NIH HHS UL1 TR002369NCATS NIH HHS UL1 TR002373NCATS NIH HHS UL1 TR002377NCATS NIH HHS UL1 TR002378NCATS NIH HHS UL1 TR002384NCATS NIH HHS UL1 TR002389NCATS NIH HHS UL1 TR002489NCATS NIH HHS UL1 TR002494NCATS NIH HHS UL1 TR002529NCATS NIH HHS UL1 TR002535NCATS NIH HHS UL1 TR002537NCATS NIH HHS UL1 TR002538NCATS NIH HHS UL1 TR002541NCATS NIH HHS UL1 TR002544NCATS NIH HHS UL1 TR002550NCATS NIH HHS UL1 TR002553NCATS NIH HHS UL1 TR002556NCATS NIH HHS UL1 TR002645NCATS NIH HHS UL1 TR002649NCATS NIH HHS UL1 TR002733NCATS NIH HHS UL1 TR002736NCATS NIH HHS UL1 TR003015NCATS NIH HHS UL1 TR003017NCATS NIH HHS UL1 TR003096NCATS NIH HHS UL1 TR003098NCATS NIH HHS UL1 TR003107NCATS NIH HHS UL1 TR003142NCATS NIH HHS UL1 TR003167NIAID NIH HHS K01 AI182501NIGMS NIH HHS U54 GM104938NIGMS NIH HHS U54 GM104940NIGMS NIH HHS U54 GM104941NIGMS NIH HHS U54 GM104942NIGMS NIH HHS U54 GM115371NIGMS NIH HHS U54 GM115428NIGMS NIH HHS U54 GM115458NIGMS NIH HHS U54 GM115516NIGMS NIH HHS U54 GM115677NIMH NIH HHS R01 MH131542
6 · The paper itselfAbstract
Background: 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' risk of severe post-COVID-19 outcomes. Methods: 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-month 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. Results: 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. Conclusions: 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.
Identifiers
PMID41822694
PMCPMC12976917
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