codes. Massachusetts Department of Public Health and COVID-19 Dashboard provided data on COVID-19 diagnosis status, and baseline county rates, respectively. Patients with incomplete data, non-Massachusetts zip codes, and prescriptions for other immunomodulator drugs were excluded (see Supplemental Table at https://data.mendeley.com/datasets/5z2vdhzbs4/1). We used multivariable logistic regression to calculate the odds ratio (OR) of COVID-19 diagnosis by antimalarial exposure, adjusting for demographics, comorbidities, local infection rates, and specific conditions identified in early studies as risk factors for COVID-19.4,5 Pearson's chi-square and two-tailed t-tests were used for pairwise comparisons of categorical and continuous variables, respectively.
RESULTS
There were 3,074 patients with antimalarial prescriptions and 58,955 matched controls (Figure 1). Hydroxychloroquine represented 98.8% of antimalarial prescriptions (Table 1). There were 51 (1.7%) infections among antimalarial-exposed and 973 (1.6%) among controls. No protective effect for SARS-CoV-2 infection was demonstrated among antimalarial-exposed patients in the multivariate model (OR=1.06, 95% CI 0.80-1.40, P=0.70).
Ages 65-74 were less likely to have confirmed COVID-19 diagnosis than patients aged 18-44 years (OR=0.61 [0.48-0.79], P<0.001). Sex did not affect susceptibility (OR=1.05 [0.88-1.24], P=0.61). Black patients had a higher infection risk than white patients (OR=1.64 [1.35-1.98], P<0.001). Severe comorbidity burden also increased SARS-CoV-2 infection risk (OR=2.32 [1.92-2.81], P<0.001). Local infection rates predicted SARS-CoV-2 infection (OR=1.26 [1.21-1.32], P<0.001), while median income by zip code did not (OR=0.98 [0.96-1.01], P=0.18).
Among the comorbidities analyzed, hypertension (OR=1.41 [1.21-1.63], P<0.001), congestive heart failure (OR 1.75 [1.47-2.09], P<0.001), COPD (OR=1.23 [1.06-1.42], P=0.01), and renal disease (OR=1.23 [1.03-1.47], P=0.02) were identified as independent risk factors for COVID-19. Hematologic cancer (OR=0.62 [0.44-0.87], P=0.01), metastatic cancer (OR=0.59 [0.43-0.83], P<0.01), and rheumatic disease (OR=0.79 [0.62-0.99], P=0.05) were found to have a protective effect.
DISCUSSION
We found that pre-pandemic antimalarial prescriptions were not protective of COVID-19 diagnosis among queried individuals, consistent with past evidence demonstrating these agents’ lack of efficacy as post-exposure prophylaxis.3
Antimalarials are frequently used to manage chronic cutaneous and systemic autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and juvenile idiopathic arthritis.6 Interestingly, we identified that a history of rheumatic disease - as well as hematologic cancer or metastatic cancer - was
