Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study

Ip, A.; Ahn, J.; Zhou, Y.; Goy, A. H.; Hansen, E.; Pecora, A. L.; Sinclaire, B. A.; Bednarz, U.; Marafelias, M.; Mathura, S.; Sawczuk, I. S.; Underwood, J. P.; Walker, D. M.; Prasad, R.; Sweeney, R. L.; Ponce, M. G.; LaCapra, S.; Cunningham, F. J.; Calise, A. G.; Pulver, B. L.; Ruocco, D.; Mojares, G. E.; Eagan, M. P.; Ziontz, K. L.; Mastrokyriakos, P.; Goldberg, S. L.

Background: Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting. Methods: We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching. Results: Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available. Conclusions: In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.