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Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review.
Ann Intern Med. 2020 08 18; 173(4):287-296.AIM

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.

Authors+Show Affiliations

University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and Hartford Hospital Department of Research Administration, Hartford, and School of Pharmacy, Storrs, Connecticut, and Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru (A.V.H.).University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and Hartford Hospital Department of Research Administration, Hartford, Connecticut (Y.M.R.).MedErgy HealthGroup Inc., Yardley, Pennsylvania (V.P.).Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru (J.J.B.).University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and Hartford Hospital Department of Research Administration, Hartford, and School of Pharmacy, Storrs, Connecticut (C.M.W.).

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Systematic Review
Video-Audio Media

Language

eng

PubMed ID

32459529

Citation

Hernandez, Adrian V., et al. "Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: a Living Systematic Review." Annals of Internal Medicine, vol. 173, no. 4, 2020, pp. 287-296.
Hernandez AV, Roman YM, Pasupuleti V, et al. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Ann Intern Med. 2020;173(4):287-296.
Hernandez, A. V., Roman, Y. M., Pasupuleti, V., Barboza, J. J., & White, C. M. (2020). Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. Annals of Internal Medicine, 173(4), 287-296. https://doi.org/10.7326/M20-2496
Hernandez AV, et al. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: a Living Systematic Review. Ann Intern Med. 2020 08 18;173(4):287-296. PubMed PMID: 32459529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review. AU - Hernandez,Adrian V, AU - Roman,Yuani M, AU - Pasupuleti,Vinay, AU - Barboza,Joshuan J, AU - White,C Michael, Y1 - 2020/05/27/ PY - 2020/5/28/pubmed PY - 2020/8/28/medline PY - 2020/5/28/entrez SP - 287 EP - 296 JF - Annals of internal medicine JO - Ann Intern Med VL - 173 IS - 4 N2 - 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. SN - 1539-3704 UR - https://www.unboundmedicine.com/medline/citation/32459529/Hydroxychloroquine_or_Chloroquine_for_Treatment_or_Prophylaxis_of_COVID_19:_A_Living_Systematic_Review_ L2 - https://www.acpjournals.org/doi/10.7326/M20-2496?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -