Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world
Million et al.
, Clinical Efficacy of Chloroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big..
, New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (meta analysis)
[H]CQ effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
Currently there are 36 HCQ early treatment studies
and meta analysis shows:
Million et al., 6 Jun 2020, peer-reviewed, 14 authors.
Abstract: ORIGINAL ARTICLE
Clinical efﬁcacy of chloroquine derivatives in COVID-19 infection:
comparative meta-analysis between the big data and the real world
M. Million1,2, P. Gautret1,3, P. Colson1,2, Y. Roussel1,2, G. Dubourg1,2, E. Chabriere1,2, S. Honore4,5, J.-M. Rolain1,2, F. Fenollar1,3,
P.-E. Fournier1,3, J.-C. Lagier1,2, P. Parola1,3, P. Brouqui1,2 and D. Raoult1,2
1) IHU-Méditerranée Infection, 2) Aix Marseille Université, IRD, AP-HM, MEPHI, 3) Aix Marseille Université, IRD, AP-HM, SSA, VITROME, 4) Service de
Pharmacie, Hôpital Timone, AP-HM and 5) Laboratoire de Pharmacie Clinique, Aix Marseille Université, Marseille, France
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derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020.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.
© 2020 The Author(s). Published by Elsevier Ltd.
Keywords: Chloroquine, coronavirus, coronavirus disease 2019, hydroxychloroquine, meta-analysis, severe acute respiratory syndrome
Original Submission: 8 May 2020; Revised Submission: 28 May 2020; Accepted: 4 June 2020
Article published online: 6 June 2020
Corresponding author: D. Raoult, IHU—Méditerranée Infection,
19–21 boulevard Jean Moulin, 13005, Marseille, France.
M. Million and P. Gautret are equal ﬁrst co-authors.
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