The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients

Abstract

This study investigates the association between the treatment with hydroxychloroquine and mortality in patients admitted with COVID-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with COVID-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with hydroxychloroquine, azithromycin, heparin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1449 had been discharged home from the hospitals, 240 were still admitted, and 85 had been transferred to hospitals not included in the study. Median follow-up time was 8 (IQR 5–12) days. Hydroxychloroquine had been used in 1857 patients. Hydroxychloroquine was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI): 0.44 (0.29–0.67). This association remained significant when saturation of oxygen < 90% and temperature > 37 °C were added to de model with OR 0.45 (0.30–0.68) p < 0.001, and also when all the other drugs, and time of admission, were included as covariates. The association between hydroxychloroquine and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized-controlled trials to assess the causal effects of hydroxychloroquine in different therapeutic regimes are required.

Disentangling the association of hydroxychloroquine treatment with mortality in Covid-19 hospitalized patients through Hierarchical Clustering

“…Specifically, we tested and observed both additive and interactive associations of HCQ and Covid-19 subtypes. Indeed, the high risk cluster was consistently associated with increased mortality across all models, while treatment with HCQ was generally associated with a halving of death risk, in line with previous evidence from both observational [6][7][8][9][10][11][12][13] and intervention studies [19]. While we already reported evidence suggesting a protective influence of HCQ against mortality in a largely overlapping sample [13], here we have further deepened this relationship by testing and reporting a significant association between cluster-by-HCQ interaction and mortality, which was driven by a differential association within the two clusters.…”

“…Despite these elements and initial suggestive evidence of efficacy based on daily clinical practice, in the last months the potential benefit of HCQ for Covid-19 patients has been harshly debated [3,5]. In particular, evidence supporting protective effects from observational studies [6][7][8][9][10][11][12][13] was in contrast with that suggesting no effect at all by recent randomized clinical trials (RCTs) [14][15][16][17][18].…”

Rationale for azithromycin in COVID-19: an overview of existing evidence

“…Guérin et al 73 one retrospective study: Guérin et al 73 Studies neutral to AZ six retrospective studies: Kuderer et al 71 Geleris et al 92 Rosenberg et al 75 Ip et al 93 Rodriguez-Molinero et al 94 Lammers et al 95 five retrospective studies: Satlin et al 96 Ip et al 93 Magagnoli et al 97 Ayerbe et al 98 Young et al 99 two retrospective studies: Kuderer et al 71 Szente et al 74 1 RCT: Cavalcanti et al 76 1 RCT: Furtado et al 100 Studies not favouring AZ 2 Retrospective studies: Kuderer et al 71 Rosenberg et al 75 one retrospective study: Kuderer et al 71 1 RCT: Cavalcanti et al 76 PubMed was searched with the search term ('COVID-19' or 'SARS-CoV-2') and 'azithromycin'. A total of 537 titles and/or abstracts were screened.…”

Low dose hydroxychloroquine is associated with lower mortality in COVID-19: a meta-analysis of 26 studies and 44,521 patients

“…In attempting to account for baseline differences between patients who received HCQ and those who did not, we used the results for adjusted measure of association for each study, and this was possible for 22 out of 26 studies included in the meta-analysis. After the exclusion of 3 unadjusted studies [16,21,24], the strength of the overall association of HCQ with mortality was merely reduced from 0.79 to 0.80. Although we attempted to control for potential confounding factors inherent to patient and clinical characteristics, it is possible that unmeasurable confounding still remains, and this may explain the different finding between observational and RCT studies.…”