Clinical efficacy of chloroquine derivatives in COVID-19 infection: comparative meta-analysis between the big data and the real world

Abstract

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020. The keywords ‘hydroxychloroquine’, ‘chloroquine’, ‘coronavirus’, ‘COVID-19’ and ‘SARS-Cov-2’ were used in the PubMed, Google Scholar and Google search engines without any restrictions as to date or language. Twenty studies were identified involving 105 040 patients (19 270 treated patients) from nine countries (Brazil, China, France, Iran, Saudi Arabia, South Korea, Spain and the USA). Big data observational studies were associated with conflict of interest, lack of treatment dosage and duration, and absence of favourable outcome. Clinical studies were associated with favourable outcomes and details on therapy. Among clinical studies, three of four randomized controlled trials reported a significant favourable effect. Among clinical studies, a significant favourable summary effect was observed for duration of cough (OR 0.19, p 0.00003), duration of fever (OR 0.11, p 0.039), clinical cure (OR 0.21, p 0.0495), death (OR 0.32, p 4.1 × 10 −6 ) and viral shedding (OR 0.43, p 0.031). A trend for a favourable effect was noted for the outcome ‘death and/or intensive care unit transfer’ (OR 0.29, p 0.069) with a point estimate remarkably similar to that observed for death (∼0.3). In conclusion, a meta-analysis of publicly available clinical reports demonstrates that chloroquine derivatives are effective to improve clinical and virological outcomes, but, more importantly, they reduce mortality by a factor of 3 in patients with COVID-19. Big data are lacking basic treatment definitions and are linked to conflict of interest. The retraction of the only big data study associated with a significantly deleterious effect the day after (June 5, 2020) the acceptance of the present work (June 4, 2020) confirms the relevance of this work.

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

“…Finally, two more RCTs have reported no association between HCQ and virological clearance [39] or prevention of disease in individuals exposed to it [40]. A number of factors could explain the difference between our results and the ones observed in these studies [32][33][34][35][36][37][38][39][40] including the following: the clinical-epidemiological design of our work; [30] the involvement of all patients admitted with COVID-19, regardless their past medical history, the time between onset of symptoms and the start of treatment, the duration of admission, and the need for oxygen; the different statistical approach; and the observation in our work of patients from private hospitals, who are likely to have a high socioeconomic status [41]. The safety of the HCQ has been questioned, as it could negatively impact the immune response to the virus, or cause abnormalities in the ECG [33,42,43].…”

Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications

“…Other studies have reported no positive effects [100]. One meta-analysis of publicly available clinical reports suggests that chloroquine derivatives are effective in reducing mortality by a factor of 3 in patients infected with COVID-19 [101]. Few studies, however, have looked at CNS effects.…”

Covid-19 et ambiguïtés autour des termes franco-malagasy devenus populaires à Madagascar

“…Pour une crédibilité scientifique des conclusions sur le fondement ou non d'une hypothèse donnée, l'existence de patients sous traitement « placebo » figure parmi les prérequis méthodologiques lors d'un test clinique. Tel a été le cas du test sur l'hydrochloroquine (HCQ), une molécule considérée efficace pour traiter la Covid-19 (Million et al, 2020 ;Lagieret al, 2020), qui, après comparaison statistique entre les résultats obtenus auprès d'un groupe sous placebo et d'un autre traité avec de l'HCQ, s'est avérée non concluant, voire médicalement dangereuse (Horby & Mandray, 2020 ;Boulware et al, 2020 ;Skipper et al, 2020 ;Hoffmann et al, 2020 ;Maisonnasse et al, 2020 ;Cavalcanti et al, 2020). Fioletet al (2020) viennent même de démontrer dans leur méta-analyse que prendre de l'hydroxychloroquine contre la Covid-19 ne sert à rien, et que l'association HCQ -azithromycine augmenterait le risque de mourir.…”