Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2
drug discovery/repurposing therapeutics
Authors: Rosenke et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.06.10.145144v1
Journal/ Pre-Print: BioRxiv
Tags: Therapeutics, Drug discovery/ Drug repurposing
The Hydroxychloroquine inhibits SARS-CoV-2 replication in Vero E6 cells.
Hydroxychloroquine prophylaxis/treatment showed no beneficial effect in SARS-CoV-2 hamster and macaque disease models.
Hydroxycloroquine has been used extensively to treat COVID-19 patients, however the evidence for HCQ efficacy in treatment of COVID-19 remains contentious. This study confirmed that HCQ displayed antiviral acvitity in Vero E6 cell line, as many other studies have suggested before. However, despite the promising in vitro effect, the administration of hydroxychloroquine either as prophylaxis or treatment at standard human malaria dose did not have any significant impact on SARS-CoV-2 replication or disease manifestation in two animal models, the Syrian hamster and the rhesus macaque models. This study do not support the use of HCQ in prophylaxis/treatment of COVID-19 and raises again the question about efficacy and safety of hydroxychloroquine in COVID-19 treatment.
Impact for SARS-CoV2/COVID19 research efforts
Treatment of SARS-CoV2/COVID19 positive individuals: The authors provide a warning for the use of the HCQ in prophylaxis or treatment of COVID-19. The authors showed that HCQ has no significant benefit on the clinical outcome of the disease nor on SARS-CoV-2 replication or shedding in hamster and macaque disease models.
In vitro study
In vivo study (Syrian hamster and Rhesus macaque)
Strengths and limitations of the paper
Novelty: The novelty of the study was to address the efficacy of HCQ in prophylaxis and treatment in two different animal models. The rhesus macaque model has been used in a study by P. Maisonnasse et al (https://www.researchsquare.com/article/rs-27223/v1) whille the data in the hamster model is novel.
Standing in the field: Although, hydroxychloroquine treatment during the COVID-19 pandemic is widespread, its use to treat COVID-19 has been controversial since the results of the first clinical trials. Most of the more recent studies, including the data proposed here, do not support the use of the HCQ in this pandemic.
Appropriate statistics: Yes
Viral model used: Syrian hamster and Rhesus macaque were infected with SARS-CoV-2 isolate nCoV-WA1-2020 (MN985325.1) via intratracheal, intranasal, oral and ocular routes.
Translatability: The results are translatable. Recently, the use of HCQ was excluded in some clinicl trials, such as the WHO Solidarity study. However, some trials are continuing to assess the efficacy of HCQ in patients, and some hospitals are continuing to offer HCQ as treatment. .
The drug efficacy in animal models might be different from the drug efficacy in humans.
The aged of the animals used were not mentioned.
The timeframes at which they begin prophylactic/treatment with HCQ are unlikely to to be translatable to human patients. For example, if patients were to take HCQ prophylactically it is unlikely that they will take a single dose 24 hours prior to infection, rather it is likely that a protracted course of HCQ would be taken. Likewise, it is unlikely that any patient would be able to access HCQ in the hour immediately following exposure to the virus; instead treatment is likely to occur following the onset of symptoms.