Investigation of clinical characteristics of COVID-19 infection in rheumatoid patients on immunosuppressive drugs: a retrospective case–control study

Abstract Backgrounds Cytokine storm has been considered a major pathogenic in severe COVID-19 patients with severe disease. Inflammatory cytokines, such as interleukin-6(IL-6), IL-1, and tumor necrosis factor alpha (TNF-α) released from the lung epithelium during COVID-19 infection resemble those involved in inflammatory rheumatic diseases. Immunosuppressive drugs are central in managing any rheumatologic diseases. Immunosuppressive drugs are central in managing any rheumatologic diseases, and prolonged use may alter clinical features of COVID-19 in these patients. Objective To determine the clinical findings and disease severity of COVID-19 infection in patients with rheumatic diseases under immunosuppressive therapy. Method A retrospective case–control study of 981 patients with rheumatic diseases attending university—affiliated clinics and hospital in Shiraz, Iran, including 539 patients with confirmed COVID-19 infection and 442 COVID-19—negative controls without documented infection. Results Pre-exposure to prednisolone was associated with increased severity of COVID-19 (adjusted OR 2.52; 95% CI 1.19–4.26). Methotrexate (MTX) use was associated with milder disease (OR 0.35; 95% CI 0.21–0.58). Among biologic therapies, anti-TNF agents (etanercept, infliximab) users showed a significant association with lower severity (OR 0.33; 95% CI 0.16–0.69), whereas the smaller rituximab (anti-CD20) subgroup ( n = 54) was insufficiently powered for separate analysis. Other conventional DMARDs showed no significant effect. Hydroxychloroquine did not show protective effects. Conclusion In this cohort of Iranian patients with rheumatic diseases, prior corticosteroid use was associated with increased COVID-19 incidence and severity, whereas MTX and anti-TNF biologics were associated with milder disease outcomes. Due to sample size limitations and contrasting literature on rituximab (anti-CD20), we caution against generalizing protective effects across all biologics. Our findings suggest that immunosuppressive therapy influences COVID-19 outcomes, but prospective studies are needed to elucidate mechanisms and causality.