Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Abstract

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19.

Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality.

Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses.

Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry.

Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

Keywords: COVID-19; Disease severity; Hydroxychloroquine; Inflammation; Mortality.

Fig. 1

The unadjusted standardized differences and standardized differences adjusted by propensity scores between HCQ-treated and non-HCQ treated patients for the variables included in the propensity score. All differences for the matched observations are within the recommended limits of –0.25 and 0.25, which are indicated by reference lines.

Fig. 2

Survival curves according to hydroxychloroquine use. The curves are adjusted by propensity score analysis (inverse probability for treatment weighting) and hospital index as random effect, and are generated using the first imputed dataset. The other imputed datasets are similar and thus omitted.