Incidence of SARS-CoV-2 in Patients with Rheumatic Diseases on Hydroxychloroquine, Compared with the Incidence of SARS-CoV-2 in Controls on a Prophylactic Dose of Hydroxychloroquine

Background: Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic drug used in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and other autoimmune diseases. Although HCQ reduces SARS-CoV-2 replication in vitro at high doses, its prophylactic role in COVID-19 remains unproven. This study evaluated SARS-CoV-2 incidence in patients with rheumatic diseases on therapeutic HCQ versus healthy controls taking HCQ prophylactically. Materials and Methods: In this prospective case-control study, 145 patients with autoimmune diseases (RA, SLE, Sjogren’s syndrome, MCTD) taking HCQ (200–400 mg/day) were compared with 77 healthy volunteers on prophylactic HCQ (400 mg/week). Participants underwent SARS-CoV-2 PCR and serology testing over one year (Feb 2020–Mar 2021). Results: SARS-CoV-2 positivity was observed in 24/145 (16.6%) patients versus 4/77 (5.2%) controls (χ² = 4.90, p = 0.027; Fisher’s exact p = 0.018; OR ≈ 3.62). All positive cases in both groups experienced mild disease without hospitalization. Conclusions: Therapeutic HCQ in patients with autoimmune diseases did not prevent SARS-CoV-2 infection as effectively as low-dose prophylactic HCQ in healthy controls. Nevertheless, disease severity was mild in all cases, supporting the overall safety of HCQ. Larger, randomized studies are needed to clarify HCQ’s prophylactic potential.