Covid-19: Intracellular observation of reconstituted human respiratory epithelium MucilAir™ infected with SARS-CoV-2. © Manuel Rosa-Calatrava, Inserm; Olivier Terrier, CNRS; Andrés Pizzorno, Signia Therapeutics; Elisabeth Errazuriz-Cerda UCBL1 CIQLE. VirPath (International Center for Research in Infectiology U1111 Inserm – UMR 5308 CNRS – ENS Lyon – UCBL1). Colorized by Noa Rosa C.
The results of a study on the effects of hydroxychloroquine, associated or not with azithromycin, in an experimental infection model in macaque by the SARS-CoV-2 virus, the infectious agent responsible for the pandemic of COVID-19, are the subject of a publication in the journal Nature July 22, 2020. Bringing together scientists from CEA, Inserm, Institut Pasteur, CNRS, Université de Paris-Saclay, AP-HM, Université Claude Bernard Lyon 1 and Aix-Marseille University, the study was carried out under the aegis of the multidisciplinary REACTing consortium1.
This study, launched in February 2020, aimed to assess the potential antiviral effect in vivo of hydroxychloroquine (HCQ), as a prophylactic treatment against the SARS-CoV-2 virus (before infection to reduce the viral load) and during first days after infection. The potential anti-inflammatory effects of HCQ have not been analyzed.
The first step aimed to demonstrate the relevance of the animal model selected. It has shown that the disease observed in non-human primates is very similar to that observed in the majority of patients with COVID-19 who do not require hospitalization.
The second step concerned the characterization of the pharmacokinetics of HCQ, that is to say the analysis of its concentration in the blood and tissues to ensure that it reached a level comparable to that observed in human patients treated with the drug.
Finally, different treatment strategies were tested for prevention (before infection of animals), immediately after infection, and finally at a distance from infection (D + 5 after infection – at the time of the appearance of symptoms), with or without azithromycin, an antibiotic also used in the treatment of COVID-19. Different treatment doses have also been tested in certain groups of animals.
The results indicate that HCQ did not protect animals when used for infection prevention. None of the strategies has also demonstrated a significant effect on the amounts of SARS-CoV-2 virus circulating in the body compared to those detected in animals treated with a placebo.
The study therefore shows that HCQ, which has antiviral properties in certain in vitro tests (using cultured cells), has no antiviral efficacy in vivo in the macaque under the specific conditions of these work, despite significant pulmonary exposure.
This preclinical study is complementary to clinical studies on HCQ. Indeed, it made it possible to better understand the physiopathological mechanisms of the SARS-CoV-2 virus and to obtain precise information on the biodistribution of the HCQ molecule in the organism of a model animal.
1 REACTing is a multidisciplinary consortium bringing together the partners of the Aviesan Alliance for Life and Health Sciences (CEA, CNRS, INRAE, Inria, Inserm, Institut Pasteur, IRD, CPU and Conference of General Managers of Regional Hospitals and academics) and coordinated by Inserm.
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