Background: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. Methods: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and > 10 day hospitalization) and viral shedding persistence (> 10 days). Results: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 yearsrange 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective betablocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). Conclusion: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.

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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2019 (COVID-19) pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020.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.

Highlights Comparison of incidence and mortality rates of four common coronaviruses circulating in France with those of SARS-COV-2 in OECD countries. As of 2 March 2020, 90 307 patients had tested positive for SARS-CoV-2 worldwide, with 3086 deaths (mortality rate 3.4%). As of 2 March 2020, among OECD countries, 7476 patients had tested positive for SARS-CoV-2, with 96 deaths (mortality rate 1.3%)  As of 2 March 2020, in France, 191 people had tested positive for SARS-CoV-2, with three deaths (mortality rate 1.6%). In OECD countries. the mortality rate for SARS-CoV-2 (1.3%) is not significantly different from that for common coronaviruses identified at the study hospital in France (0.8%; P=0.11). The problem of SARS-CoV-2 is probably overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4000 deaths for SARS-CoV-2 at the time of writing. ABSTRACT SARS-CoV-2, the novel coronavirus from China, is spreading around the world, causing a huge reaction despite its current low incidence outside China and the Far East. Four common coronaviruses are in current circulation and cause millions of cases worldwide. This article compares the incidence and mortality rates of these four common coronaviruses with those of SARS-COV-2 in Organisation for Economic Co-operation and Development countries. It is concluded that the problem of SARS-CoV-2 is probably being overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4000 deaths for SARS-CoV-2 at the time of writing.

Funding and gifts from the pharmaceutical industry have an influence on the decisions made by physicians and medical experts. In the context of the coronavirus disease 2019 epidemic, several treatments are available to treat patients infected with the virus. Some are protected by patents, such as remdesivir, others0020stare not, such as hydroxychloroquine. We wanted to observe the possible correlation between the fact, for an academic doctor in infectious diseases, of having benefited from funding by Gilead Sciences, producer of remdesivir, and the public positions taken by this doctor towards hydroxychloroquine. Our results show a correlation (Spearman test, p = 0.017) between the amount received from the Gilead Sciences company and public opposition to the use of hydroxychloroquine in France. This should open up the debate on the role of the interest links of doctors with pharmaceutical companies in the medical and scientific public debate.

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Background: The COVID-19 pandemic led to a violent debate about the efficacy of a repurposed drug hydroxychloroquine (HCQ) and a new broad-spectrum antiviral (remdesivir) and about randomized controlled trials (RCTs) and observational studies. To understand conflicting results in the literature, we performed a meta-synthesis to determine whether intrinsic qualitative criteria within studies may predict apparent efficacy or ineffectiveness of HCQ and remdesivir. Methodology: Predictive criteria were identified through critical review of studies assessing HCQ and remdesivir for COVID-19 mortality from March to November 2020. Multiple correspondence analysis, comparative meta-analysis, and predictive value were used to explore and identify criteria associated with study outcomes. Results: Among the 61 included studies, potential conflict of interest, detailed therapeutic protocol, toxic treatment (overdose or use in contraindicated patients), known centers and doctors, and private data computing company were the most predictive criteria of the direction of effect of the studies. All 18 observational studies evaluating HCQ and reporting detailed therapeutic protocol without conflict of interest were Pro. Potential conflict of interest was a perfect predictor for remdesivir efficacy. RCTs were associated with HCQ inefficacy and potential conflict of interest. The most predictive criteria were validated and allowed perfect classification of 10 additional studies.Conclusion: In therapeutic trials on COVID-19, the major biases predicting the conclusions are not methodology nor data analysis, but conflict of interest and absence of medical expertise. The thorough search for declared or undeclared and direct or indirect conflict of interest, and medical expertise should be included in the quality criteria for the evaluation of future therapeutic studies in COVID-19 and beyond. A new checklist evaluating not only methodology but also conflict of interest and medical expertise is proposed.