A matched-cohort study of treatment-requiring autoimmune rheumatic diseases after COVID-19

Post-coronavirus disease-2019 (COVID-19) symptoms can resemble autoimmune and inflammatory rheumatic diseases (AIIRDs), and claims-based studies using diagnosis codes alone may misclassify transient or uncertain diagnoses. The combination of an AIIRD diagnosis and initiated disease-relevant therapy may more accurately identify patients requiring treatment. We aimed to determine whether a history of COVID-19 was associated with a higher 1-year incidence of treatment-requiring AIIRDs compared to matched individuals without COVID-19. We conducted a matched cohort study using the nationwide JMDC Claims Database in Japan, including inpatient, outpatient, and pharmacy data, from July 1, 2019, to August 31, 2023, with 12 months of observation after the index month. Individuals with confirmed COVID-19 and at least 12 months of claims data after the index month were matched 1:1 to individuals without COVID-19 on age, sex, severe-disease risk factors, and Charlson Comorbidity Index; individuals with COVID-19 or AIIRDs in the previous 6 months were excluded. The matched cohorts included 770,498 participants each, and the matched analysis population included 764,454 participants per group. The primary outcome was incident treatment-requiring AIIRD within 12 months, defined by an AIIRD diagnosis code plus initiation of immunosuppressants and/or disease-specific medications. The secondary outcome was AIIRD-related hospitalization. Risk differences and risk ratios with 95% confidence intervals were estimated. Among 1,528,908 participants, incident treatment-requiring AIIRDs occurred in 1,591 individuals (0.21%) with COVID-19 vs. 817 (0.11%) in those without COVID-19 (risk difference, 0.101% points [95% CI, 0.089–0.114]; risk ratio [RR], 1.95 [95% CI, 1.79–2.12]). AIIRD-related hospitalization occurred in 283 individuals (0.037%) with COVID-19 vs. 15 (0.002%) in those without COVID-19 (risk difference, 0.035% points [95% CI, 0.031–0.039]; RR, 18.87 [95% CI, 11.22–31.71]). In diagnosis-specific analyses, notably, risks were higher for rheumatoid arthritis (RR, 1.92 [95% CI, 1.71–2.15]), Sjögren’s syndrome (RR, 1.49 [95% CI, 1.24–1.79]), and antineutrophil cytoplasmic antibody-associated vasculitis (RR, 4.90 [95% CI, 2.48–9.67]). This study revealed a higher 1-year incidence of treatment-requiring AIIRDs and markedly higher AIIRD-related hospitalization associated with COVID-19. These findings support clinical vigilance for inflammatory rheumatic disease requiring treatment after COVID-19.