RESUMEN
Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease1-3. 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 infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-194-7. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.
Asunto(s)
Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Animales , Azitromicina/farmacología , Azitromicina/uso terapéutico , COVID-19 , Chlorocebus aethiops , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/fisiopatología , Citocinas/sangre , Modelos Animales de Enfermedad , Femenino , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/farmacología , Técnicas In Vitro , Cinética , Macaca fascicularis , Masculino , Pandemias , Neumonía Viral/patología , Neumonía Viral/fisiopatología , Profilaxis Pre-Exposición , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/virología , SARS-CoV-2 , Factores de Tiempo , Insuficiencia del Tratamiento , Células Vero , Carga Viral/efectos de los fármacos , Tratamiento Farmacológico de COVID-19RESUMEN
We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than 2 logs, drug efficacy needs to be greater than 80% if treatment is administered after symptom onset; an efficacy of 50% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 20-70% efficacy. They may help control virus if administered very early, but may not have a major effect in severe patients.