• Fernando S Velayos, Jennifer R Dusendang, and Julie A Schmittdiel.
• Division of Gastroenterology and Hepatology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA. Fernando.Velayos@kp.org.
• J Gen Intern Med. 2021 Dec 1; 36 (12): 3794-3801.

BackgroundAn estimated 10 million people in the USA are immunocompromised, a risk factor for severe COVID-19. Data informing whether immune-mediated medications lead to more severe infection are sparse.ObjectiveDetermine whether outpatient immunosuppressive therapies that treat autoimmune inflammatory disease or prevent solid organ transplant rejection are associated with severe illness after diagnosis with SARS-CoV-2 DESIGN: Retrospective cohort study PARTICIPANTS: Adults with a positive PCR nasal swab for SARS-CoV-2 from February 25 to September 9, 2020, cared for within a large integrated health care organization MAIN MEASURES: Exposure was defined as an outpatient fill of prednisone, immunomodulator, small-molecule, or biologic therapy in the 105 days prior to a positive SARS-CoV-2 PCR test. The main outcome was either hospitalization, ICU admission, or death within 45 days after diagnosis of SARS-CoV-2. Multivariable logistic regression models were adjusted for age, race, gender, body mass index, comorbidities, and autoimmune disease.Key ResultsA total of 39,686 adults had a positive PCR test. In the primary analysis, prior prednisone use was associated with severe illness after diagnosis with SARS-CoV-2 (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.08-1.60); however, immunomodulator (OR 0.88; 95% CI 0.57-1.34) and biologic/small-molecule therapy (OR 1.26; 95% CI 0.79-2.00) were not. Secondary analyses showed variable risk among therapies: Janus-kinase inhibitors had an increased odds of severe illness (OR 3.35; 95% CI 1.16-9.67), thiopurines/conventionaldisease-modifying antirheumatic drugs had a reduced odds (OR 0.53; 95% CI 0.32-0.88), and tumor necrosis factor inhibitors were not associated (OR 0.45; 95% CI 0.18-1.08).Conclusions And RelevanceOutpatient use of prednisone is associated with severe illness after diagnosis of SARS-CoV-2. Immunomodulator and biologic/small-molecule therapy were not associated, but different risk subgroups were identified. Our findings can inform risk-benefit discussions in the clinic and risk-based recommendations for patients on these therapies.© 2021. Society of General Internal Medicine.

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