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Research Article
Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non-human primates
Roger Le Grand
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Corresponding Author
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COVID-19 has become a pandemic that has caused over 200,000 deaths worldwide, with no antiviral drug or vaccine yet available. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive evidence for HCQ efficacy in treatment of COVID-19 is still missing.
We evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in monkey African green monkey kidney (VeroE6) cells but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to placebo, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor HCQ+AZTH showed a significant effect on the viral load levels in any of the tested compartments. When the drug was used as a pre-exposure prophylaxis (PrEP), HCQ did not confer protection against acquisition of infection.
Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans.
Keywords
SARS-CoV-2, macaques, hydroxychloroquine, azithromycin, viral load levels
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Francis MARTY
commented on 31 May, 2020
I may be confused but could you make clear the number of animals assigned in each balanced experimental group?
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This preprint is under consideration at a Nature Portfolio Journal. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Nature journals have partnered with Research Square to offer In Review, a journal-integrated preprint deposition service.
Research Article
Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non-human primates
Roger Le Grand
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases » (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 06 May, 2020
Metrics
Comments: 2
PDF Downloads: ...
HTML Views: ...
Subject Areas
Virology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
COVID-19 has become a pandemic that has caused over 200,000 deaths worldwide, with no antiviral drug or vaccine yet available. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive evidence for HCQ efficacy in treatment of COVID-19 is still missing.
We evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in monkey African green monkey kidney (VeroE6) cells but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to placebo, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor HCQ+AZTH showed a significant effect on the viral load levels in any of the tested compartments. When the drug was used as a pre-exposure prophylaxis (PrEP), HCQ did not confer protection against acquisition of infection.
Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral treatment for COVID-19 in humans.
Figure 1
Figure 2
Figure 3
Figure 4
Francis MARTY
commented on 31 May, 2020
I may be confused but could you make clear the number of animals assigned in each balanced experimental group?
View 1 reply
Anne Onyme
replied on 09 June, 2020
RTFM: control group 8, HCQ 9
Anne Onyme
replied on 09 June, 2020
RTFM: control group 8, HCQ 9