Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohorts

SARS-CoV-2 infection has been associated with increased autoimmune disease risk. Past studies have not aligned regarding the most prevalent autoimmune diseases after infection, however. Furthermore, the relationship between infection severity and new autoimmune disease risk has not been well examined. We used RECOVER's electronic health record (EHR) networks, N3C, PCORnet, and PEDSnet, to estimate types and frequency of autoimmune diseases arising after SARS-CoV-2 infection and assessed how infection severity related to autoimmune disease risk. We identified patients of any age with SARS-CoV-2 infection between April 1, 2020 and April 1, 2021, and assigned them to a World Health Organization COVID-19 severity category for adults or the PEDSnet acute COVID-19 illness severity classification system for children (<age 21). We collected baseline covariates from the EHR in the year pre-index infection date and followed patients for 2 years for new autoimmune disease, defined as ≥ 2 new ICD-9, ICD-10, or SNOMED codes in the same concept set, starting >30 days after SARS-CoV-2 infection index date and occurring ≥1 day apart. We calculated overall and infection severity-stratified incidence ratesper 1000 person-years for all autoimmune diseases. With least severe COVID-19 severity as reference, survival analyses examined incident autoimmune disease risk. The most common new-onset autoimmune diseases in all networks were thyroid disease, psoriasis/psoriatic arthritis, and inflammatory bowel disease. Among adults, inflammatory arthritis was the most common, and Sjögren's disease also had high incidence. Incident type 1 diabetes and hematological autoimmune diseases were specifically found in children. Across networks, after adjustment, patients with highest COVID-19 severity had highest risk for new autoimmune disease vs. those with least severe disease (N3C: adjusted Hazard Ratio, (aHR) 1.47 (95%CI 1.33-1.66); PCORnet aHR 1.14 (95%CI 1.02-1.26); PEDSnet: aHR 3.14 (95%CI 2.42-4.07)]. Overall, severe acute COVID-19 was most strongly associated with autoimmune disease risk in three EHR networks.