Prior Immunosuppressive Therapy and Severe Illness Among Patients Diagnosed with SARS-CoV-2: a Community-Based Study

Velayos, Fernando S.; Dusendang, Jennifer R.; Schmittdiel, Julie A.

BACKGROUND: An 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. OBJECTIVE: Determine 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 RESULTS: A 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 RELEVANCE: Outpatient 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07152-2.