key: cord-0710603-n6juf8tw
authors: Kalligeros, Markos; Shehadeh, Fadi; Atalla, Eleftheria; Mylona, Evangelia K.; Aung, Su; Pandita, Aakriti; Larkin, Jerry; Sanchez, Martha; Touzard-Romo, Francine; Brotherton, Amy; Shah, Rajeev; Cunha, Cheston B.; Mylonakis, Eleftherios
title: Hydroxychloroquine use in Hospitalized Patients with COVID-19: An observational matched cohort study
date: 2020-08-05
journal: J Glob Antimicrob Resist
DOI: 10.1016/j.jgar.2020.07.018
sha: 27587d8e919a9fc18c62a2eea24a6bbad97a0153
doc_id: 710603
cord_uid: n6juf8tw

• The efficacy of HCQ in patients with COVID-19 is currently evaluated. • In our center the use of HCQ did not decrease the risk of in-hospital death. • HCQ use did not decrease the time to clinical improvement and the hospitalization length. • ASPs can allow for the safe evaluation of agents and treatments against COVID-19.

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Hydroxychloroquine (HCQ) and chloroquine (CQ) were among the first drugs that emerged as potential therapeutic options against COVID-19. These two antimalarial drugs, also commonly used as immunomodulators in the setting of rheumatologic diseases, showed in vitro activity against SARS-CoV-2 [1, 2] . Our aim was to assess the efficacy and safety of hydroxychloroquine (HCQ) with or without azithromycin (AZ) in hospitalized adult patients with COVID-19.

We utilized data from the largest healthcare network in Rhode Island, USA, with the aim of exploring the efficacy and safety of HCQ in hospitalized patients with COVID-19. The primary end point was to assess the impact of HCQ with or without AZ, on mortality, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverseprobability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities.

There were no significant differences between the two groups in terms of illness severity at the time of hospital admission (Table 1 ). In our inverse probability analyses we 

We utilized Cox proportional hazards models to estimate in-hospital risk of death due to COVID-19. In our unadjusted model, compared to the supportive care arm, HCQ did not decrease the risk of in-hospital death (HR:1.10; 95% CI: 0.31-3.93). Moreover, HCQ did not seem to decrease the risk of death even after adjusting for age, gender and race (aHR 0.82; 95% CI: 0.20-3.24) as well as days from symptoms onset, NEWS and van Walraven scores (aHR 1.67; 95% CI: 0.29-9.36). Finally, using Schoenfeld residuals method we tested proportionality and we didn't identify violations of the proportional hazard assumption in any of our models.

Among 36 patients who received HCQ, 32 patients received HCQ along with azithromycin, while 4 patients received HCQ monotherapy due to prolonged QTc on baseline.

Five patients did not complete their 5-day regimen. The reasons behind discontinuing HCQ were as follows: 1 patient developed QTc prolongation (484 ms) (day 3), 1 patient died due to COVID-19 (day 3), 1 patient developed bradycardia (day 4), in 1 patient the treating team discontinued the drug due to possible contribution to patient's altered mental status (day 3), while in 1 patient the treating team decided to discontinue the drug due to seizure activity during hospitalization (day 4). In addition, although not included in our analysis, due to the receipt of <4 doses, one patient discontinued HCQ after 3 doses due to QT prolongation (453 ms) and the development of premature ventricular contractions. After performing a paired ttest we observed a QTc prolongation from a baseline of 444 ± 26 ms (mean ± SD) to 464 ± 32 ms (mean ± SD) (P < 0.001). A comparison between HCQ monotherapy and HCQ with azithromycin was not performed due to the small number of patients receiving HCQ monotherapy. Finally, among patients who completed their 5-day regimen 3 patients developed a QTc >500 ms. None of the included patients developed torsades de pointes.

Overall, this study did not yield definite benefits from HCQ use in patients with COVID-19, but the results should be interpreted with caution due to the limited sample size. A recent report from the US with 1376 patients, of whom 811 (58.9%) received HCQ, found no J o u r n a l P r e -p r o o f 

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