Hydroxychloroquine May Not Be Associated With Preventive Effect Against SARS-CoV-2 Infection in Rheumatic Diseases

Possible Unproven Treatment To COVID-19
Researchers investigated the risk for SARS-CoV-2 infection in patients with rheumatic disease receiving vs not receiving hydroxychloroquine.

Hydroxychloroquine (HCQ) may not be associated with a preventive effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with rheumatic diseases, according to study results published in Lancet Rheumatology. However, researchers noted that overall mortality was reduced among patients receiving HCQ vs those who were not.

Researchers conducted a retrospective cohort study to evaluate whether patients with rheumatic diseases receiving vs not receiving treatment with HCQ were at reduced risk of developing SARS-CoV-2 infection. Inclusion criteria were patients (aged ≥18 years) enrolled in the Veterans Health Administration who were alive as of March 1, 2020, and had International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes for rheumatoid arthritis, systemic lupus erythematosus, and associated rheumatologic conditions. Researchers calculated a propensity score for each patient receiving HCQ who was matched with 2 patients not receiving HCQ. Primary outcome was proportion of SARS-CoV-2 infection in the treatment and control group; secondary outcomes included hospital admission, intensive care requirement and mortality associated with SARS-CoV-2, and hospital admission and mortality because of any other causes.

The study cohort included 10,703 patients receiving HCQ (mean age, 64.8±12.9 years; 75.0% men) and 214,406 patients not receiving HCQ (mean age, 65.4±13.3 years; 77.1% men). Incidence of active SARS-CoV-2 infections did not differ between the treatment and control group (n=31 [0.3%]/10,703 vs n=78 [0.4%]/21,406, respectively; odds ratio [OR], 0.79; 95% CI, 0.52-1.20; P =.27).

In terms of secondary outcomes, overall hospital admission did not differ between the 2 groups; however, overall mortality was lower among patients receiving vs not receiving HCQ (OR, 0.70; 95% CI, 0.55-0.89; P =.0031).

Multivariate logistic regression analysis showed that certain factors, including presence of polyarthritis, non-White race, urban residence, receipt of vitamin C, receipt of angiotensin-converting enzyme 2 inhibitor, elevated erythrocyte sedimentation rate, and baseline C-reactive protein levels greater than 10 ug/mL, were independently associated with SARS-CoV-2 infection. However, HCQ use was not independently associated with SARS-CoV-2 infection (OR, 0.79; 95% CI, 0.51-1.42).

Study limitations included the fact that only 24% of the study cohort were women and that adherence to HCQ was measured over a period of 12 months of prescriptions filled to produce a medication possession ratio, which did not account for patients taking their medications appropriately. 

Researchers concluded, “The use of observational data drawn rapidly from large clinical administrative databases might be an effective strategy to identify promising agents for further research or to identify agents that might not merit more effort. Our data [add] to the expanding knowledge base that suggests that [HCQ] might not be an effective agent in the battle against SARS-CoV-2.”


Gentry CA, Humphrey MB, Thind SK, Hendrickson SC, Kurdgelashvili G, Williams II RJ. Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study. Lancet Rheumatol. Published online September 21, 2020. doi:10.1016/S2665-9913(20)30305-2