Factors Associated with Severity and Mortality of COVID-19 in Patients with Connective Tissue Diseases and Rheumatoid Arthritis: A Nation-wide, Population-based Analysis of the French National Medico-administrative SNDS Database

Objectives: To investigate the risk and predictors of severity and mortality of COVID-19 infection in patients with Connective Tissue Diseases (CTDs).

Methods: Using the French nationwide claims and hospitalization database, we assembled a nation-wide exhaustive cohort of adult CTD patients with rheumatoid arthritis, systemic lupus, Sjögren's disease, inflammatory myopathies, systemic sclerosis. We analyzed the rates of hospitalization, severe inpatient stays (intensive care unit [ICU] admissions or in-hospital mortality), and in-hospital mortality with COVID-19 from January 1st to December 31st, 2020.

Results: The study included 329,276 CTD patients (75.5% female, mean age 65.2±15.3 years). Among these, 3,389 (1.03%) were hospitalized, with COVID-19 infection, 973 (0.29%) required admission to ICU and 713 (0.22%) died. Patients who were hospitalized had severe inpatient stays, or died were predominantly male, older and with comorbidities (P<0.0001 for all). The risk of hospitalization, severe inpatient stay, and death was significantly higher in patients treated with glucocorticoids, leflunomide, sulfasalazine, mycophenolate derivatives, and rituximab (P<0.05 for all). TNF inhibitors were associated with reduced hospitalizations and severe inpatient stays (P<0.05 for all) and methotrexate use was associated with decreased mortality (P<0.01).

Conclusion: In CTD patients with COVID-19, use of glucocorticoids, rituximab, and certain immunosuppressants was associated with severity and mortality, while TNF inhibitors and methotrexate were protective. These findings can guide clinical and public health decisions for this highly vulnerable group.