Evaluation of hydroxychloroquine-based combination therapies for the treatment of COVID-19

ABSTRACT

Background: During the early COVID-19 pandemic a large number of investigational agents were utilized due to lack of therapeutic options. We evaluate the utility of commonly-used investigational agents combined with hydroxychloroquine (HCQ). Methods: This multicenter observational cohort study included patients admitted with COVID-19 between March - May 2020 in Detroit, Michigan who received at least 2 doses of HCQ. Our primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score from presentation to day 5 of HCQ therapy with a secondary outcome of in-hospital mortality. Data collected included demographics, Charlson Comorbidity index (CCI), daily SOFA score, laboratory data and COVID-directed therapies. Multiple linear regressions were performed to control for potential confounders between different therapies and change in SOFA score. Results: Three hundred thirty-five patients receiving HCQ were included. Patients were 62 ± 14.8 years of age, male (54%) and African-American (82%) with a mean CCI of 1.7 ± 1.9. In our cohort, 32% were admitted to the intensive care unit and 35% expired. Therapies received by more than 20% of patients in addition to HCQ included azithromycin (80%), zinc (76%) and vitamin D (29%). In our unadjusted analysis, a significant improvement in SOFA score was observed with zinc (0.76) while no significant change was observed with azithromycin (-0.46) or vitamin D (0.05). However, there was no significant change in SOFA score after adjusting for confounders for azithromycin, zinc and vitamin D. No difference in mortality was observed between the groups. Conclusion: Overall, no benefit in end-organ damage or mortality was observed with the addition of azithromycin, zinc or vitamin D to HCQ. Further studies are needed to confirm this observation.