tetano
Editor, Senior Moderator
Ann Intern Med
. 2020 May 27.
doi: 10.7326/M20-2496. Online ahead of print.
Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review
Adrian V Hernandez[SUP] 1 [/SUP], Yuani M Roman[SUP] 2 [/SUP], Vinay Pasupuleti[SUP] 3 [/SUP], Joshuan J Barboza[SUP] 4 [/SUP], C Michael White[SUP] 5 [/SUP]
Affiliations
Abstract
Background: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).
Purpose: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).
Data sources: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020.
Study selection: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection.
Data extraction: Independent, dually performed data extraction and quality assessments.
Data synthesis: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine.
Limitation: There were few controlled studies, and control for confounding was inadequate in observational studies.
Conclusion: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.
Primary funding source: Agency for Healthcare Research and Quality.
. 2020 May 27.
doi: 10.7326/M20-2496. Online ahead of print.
Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review
Adrian V Hernandez[SUP] 1 [/SUP], Yuani M Roman[SUP] 2 [/SUP], Vinay Pasupuleti[SUP] 3 [/SUP], Joshuan J Barboza[SUP] 4 [/SUP], C Michael White[SUP] 5 [/SUP]
Affiliations
- PMID: 32459529
- DOI: 10.7326/M20-2496
Abstract
Background: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).
Purpose: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19).
Data sources: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020.
Study selection: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection.
Data extraction: Independent, dually performed data extraction and quality assessments.
Data synthesis: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine.
Limitation: There were few controlled studies, and control for confounding was inadequate in observational studies.
Conclusion: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.
Primary funding source: Agency for Healthcare Research and Quality.