Hydroxychloroquine provides moderate COVID-19 prevention, large clinical trial shows

Published in PLOS Medicine, COPCOV found a 15% reduction in symptomatic COVID-19 in those taking the medication vs those taking a placebo. The study also showed a significant reduction in all-cause respiratory illness, as well as fewer days lost to work because of illness. Importantly, hydroxychloroquine was well tolerated and safe.

“No drug excited as much controversy during the COVID-19 pandemic as hydroxychloroquine,” said University of Oxford Professor Sir Nick White, COPCOV study co-Principal Investigator (PI), and Chair of the Wellcome Trust- Oxford Asia Research Units. “It was both widely recommended and widely reviled as a preventive without enough scientific evidence for either position.”

“While trials in hospitals showed subsequently that hydroxychloroquine was not effective in severely ill patients, its role in prevention remained uncertain, and the toxic atmosphere compromised the studies needed to find out whether it worked or not,” lamented Prof White

Sponsored by the University of Oxford and funded by Wellcome’s COVID-19 Therapeutics Accelerator, COPCOV was a double-blind placebo-controlled evaluation of hydroxychloroquine and chloroquine COVID-19 chemoprevention that recruited 4,652 participants in 26 sites in 11 countries in the UK, Africa and Asia from 2020 to 2022.

In May 2020 a widely publicized fraudulent claim that hydroxychloroquine was killing patients hospitalised with COVID-19 further fuelled the highly politicised controversy surrounding this medication, and led regulatory authorities to issue safety warnings and revoke use authorisations in COVID-19. The COPCOV study and other preventive studies evaluating hydroxychloroquine were stopped. Many study sites were unable to recover, and recruitment difficulties drastically delayed results for those that remained. [See Background.]

“Thankfully, there is no need to take hydroxychloroquine today to prevent COVID-19. The effective vaccines and natural infections have made us immune so that the disease has become mild. It was a different story early in the pandemic, however. Thanks to the research we now know hydroxychloroquine might have been able to do some good,” said COPCOV co-PI Dr Will Schilling, Research Physician and Oxford DPhil Student, based at the Mahidol Oxford Tropical Medicine Research Unit (MORU), in Bangkok.

“Completing this study was hard, but fighting a pandemic is like fighting a war. Good intelligence is crucial. Clinical research and good science need to be protected,” said Prof White.

Publication

Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial. Schilling WHK, Mukaka M, Callery JJ, Llewelyn MJ, Cruz CV, Dhorda M, Thatsanun Ngernseng, Waithira N, Ekkapongpisit M, Watson JA, Chandna A, Nelwan EJ, Hamers RL, Etyang A, Beg MA, Sow S, Yavo W, Allabi AC, Basnyat B, Sharma SK, Amofa-Sekyi M, Yonga P, Adler A, Yuentrakul P, Cope T, Thaipadungpanit J, Rienpradub P, Imwong M, Abdad MY, Blacksell SD, Tarning J, Goudjo FF, Dossou AD, Konaté-Touré A, Assi S-B, Ouffoué K, Nasronudin N, Rachman BE, Romadhon PZ, Dewanto DD, Heryana MO, Novi T, Pasaribu AP, Mutiara M, Nasution MPR, Khairunnisa K, Dalimunthe FA, Eka Airlangg E, Akmal Fahrezzy A, Yanri Subronto Y, Ananda NR, Rahardjani M, Rimainar A, Lucinde RK, Timbwa M, Onyango OE, Agutu C, Akech S, Hamaluba M, Kipyego J, Ngachi O, Haara FC, Traoré OY, Diarra F, Khanal B, Dahal P, Shrestha S, Rijal S, Kabore Y, Adehossi E, Guindo O, Qamar FN, Kazi AM, Woodrow CJ, Laird S, Cheeba M, Ayles H, Cheah PY, Taylor WRJ, Batty EM, Chotivanich E, Pukrittayakamee S, Phumratanaprapin S, von Seidlein L, Dondorp A, Day NPJ, White NJ, on behalf of the COPCOV Collaborative Group. PLoS Med. (2024) 21(9): e1004428. https://doi.org/10.1371/journal.pmed.1004428.

Background

The Surgisphere scandal: What went wrong? (Catherine Offord, The Scientist, 1 Oct 2020)

Major medical journals retract Covid-19 studies (MORU, 9 June 2020)

An open letter to Richard Horton, editor of The Lancet regarding Mehra et al (MORU, 29 May 2020)