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Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19

García-Albéniz et al., European Journal of Epidemiology, doi:10.1007/s10654-022-00891-4 (date from preprint)
Aug 2022  
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Case, PrEP 28% Improvement Relative Risk Case, PEP 9% HCQ for COVID-19  García-Albéniz et al.  META ANALYSIS c19hcq.org FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19hcq.org
Systematic review and meta-analysis of HCQ prophylaxis RCTs showing a statistically significant reduction in cases for pre-exposure prophylaxis.
For PEP trials there were very long treatment delays - in one trial about a third of participants were enrolled 4 days after exposure with an additional shipping delay of ~46 hours on average, and in another trial participants were enrolled up to 7 days after exposure, with an unknown additional delay before treatment, and results suggesting that exposure detection was delayed.
8 meta analyses show significant improvements with hydroxychloroquine for mortality1-4, hospitalization1, recovery5, combined death/hospitalization/cases6, and cases7,8.
Currently there are 39 HCQ for COVID-19 early treatment studies, showing 76% lower mortality [61‑85%], 67% lower ventilation [-710‑99%], 31% lower ICU admission [1‑53%], and 41% lower hospitalization [28‑51%].
risk of case, 28.0% lower, RR 0.72, p = 0.003, PrEP.
risk of case, 9.0% lower, RR 0.91, p = 0.45, PEP.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
García-Albéniz et al., 9 Aug 2022, peer-reviewed, 5 authors. Contact: xgarcia@rti.org.
This PaperHCQAll
Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19
Xabier García-Albéniz, Julia Del Amo, Rosa Polo, José Miguel Morales-Asencio, Miguel A Hernán
European Journal of Epidemiology, doi:10.1007/s10654-022-00891-4
Background Hydroxychloroquine (HCQ) is not an effective treatment for established coronavirus disease 2019 (COVID-19) [1, 2], but it is unclear whether HCQ can prevent symptomatic COVID-19. Early in the SARS-CoV-2 pandemic, about 30 randomized trials were designed to study HCQ as prophylaxis for COVID-19 [3] . After the findings from two of these trials were reported in the Summer of 2020 [4, 5], HCQ was generally viewed by the medical community as ineffective for COVID-19 prophylaxis. The emergence of that consensus was surprising because both trials found a lower risk of COVID-19 in the HCQ group, though they were too small to rule out either benefit or harm of HCQ. A timely completion of the remaining trials would have generated precise estimates of the potential effectiveness Xabier García-Albéniz
manuscript. All authors made substantial contributions to the design of the study, interpreted the data, revised the manuscript critically, approved the version to be published and agree to be accountable for all aspects of the work. Code is available upon request from Xabier Garcia-Albeniz (xgarcia@rti.org). Funding No funding was received to support the development of this manuscript. Declarations Competing Interests The authors have no relevant financial or nonfinancial interests to disclose. Author contribution XGA and MAH analysed the data and drafted the Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10654-022-00891-4.
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Clin Infect diseases: official publication Infect Dis Soc ' 'Am. 2020;71(15):732–9.', 'journal-title': 'Clin Infect diseases: official publication Infect Dis Soc Am'}, { 'issue': '14', 'key': '891_CR31', 'doi-asserted-by': 'publisher', 'first-page': '1391', 'DOI': '10.1056/NEJMsm1605385', 'volume': '377', 'author': 'MA Hernan', 'year': '2017', 'unstructured': 'Hernan MA, Robins JM. Per-protocol analyses of pragmatic trials. N Engl ' 'J Med. 2017;377(14):1391–8.', 'journal-title': 'N Engl J Med'}, { 'key': '891_CR32', 'doi-asserted-by': 'crossref', 'unstructured': 'Dahabreh IJ, Petito LC, Robertson SE, Hernán MA, Steingrimsson JA. ' 'Toward Causally Interpretable Meta-analysis: Transporting Inferences ' 'from Multiple Randomized Trials to a New Target Population. 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Scientists rise up against ' 'statistical significance. Nature. 2019;567(7748):305–7.', 'journal-title': 'Nature'}, { 'issue': '4', 'key': '891_CR35', 'doi-asserted-by': 'publisher', 'first-page': '337', 'DOI': '10.1007/s10654-016-0149-3', 'volume': '31', 'author': 'S Greenland', 'year': '2016', 'unstructured': 'Greenland S, Senn SJ, Rothman KJ, Carlin JB, Poole C, Goodman SN, et al. ' 'Statistical tests, P values, confidence intervals, and power: a guide to ' 'misinterpretations. Eur J Epidemiol. 2016;31(4):337–50.', 'journal-title': 'Eur J Epidemiol'}, { 'issue': '1', 'key': '891_CR36', 'doi-asserted-by': 'publisher', 'first-page': '2349', 'DOI': '10.1038/s41467-021-22446-z', 'volume': '12', 'author': 'C Axfors', 'year': '2021', 'unstructured': 'Axfors C, Schmitt AM, Janiaud P, van’t Hooft J, Abd-Elsalam S, Abdo EF, ' 'et al. Mortality outcomes with hydroxychloroquine and chloroquine in ' 'COVID-19 from an international collaborative meta-analysis of randomized ' 'trials. Nat Commun. 2021;12(1):2349.', 'journal-title': 'Nat Commun'}, { 'issue': '11', 'key': '891_CR37', 'doi-asserted-by': 'publisher', 'first-page': 'e20044', 'DOI': '10.2196/20044', 'volume': '22', 'author': 'K Niburski', 'year': '2020', 'unstructured': 'Niburski K, Niburski O. Impact of Trump’s Promotion of Unproven COVID-19 ' 'Treatments and Subsequent Internet Trends: Observational Study. J Med ' 'Internet Res. 2020;22(11):e20044.', 'journal-title': 'J Med Internet Res'}, { 'key': '891_CR38', 'first-page': 'n949-n', 'volume': '373', 'author': 'JJ Bartoszko', 'year': '2021', 'unstructured': 'Bartoszko JJ, Siemieniuk RAC, Kum E, Qasim A, Zeraatkar D, Ge L, et al. ' 'Prophylaxis against covid-19: living systematic review and network ' 'meta-analysis. BMJ (Clinical research ed). 2021;373:n949-n.', 'journal-title': 'BMJ (Clinical research ed)'}], 'container-title': 'European Journal of Epidemiology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s10654-022-00891-4.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s10654-022-00891-4/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s10654-022-00891-4.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 8, 9]], 'date-time': '2022-08-09T09:05:22Z', 'timestamp': 1660035922000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s10654-022-00891-4'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 8, 9]]}, 'references-count': 38, 'alternative-id': ['891'], 'URL': 'http://dx.doi.org/10.1007/s10654-022-00891-4', 'relation': {}, 'ISSN': ['0393-2990', '1573-7284'], 'subject': ['Epidemiology'], 'container-title-short': 'Eur J Epidemiol', 'published': {'date-parts': [[2022, 8, 9]]}, 'assertion': [ { 'value': '31 January 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '16 June 2022', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '9 August 2022', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The authors have no relevant financial or non-financial interests to disclose.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing Interests'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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