Pre-exposure prophylaxis – chloroquine in healthcare workers!

Contributed by Dr Prasanna Kumar

The role of chloroquine as a repurposed drug for Covid-19 has created more controversy recently as many governments and public health bodies approving HCQ for both prophylaxis and therapy without definite scientific evidence.

A recent non peer reviewed randomised, double blind, placebo-controlled trial by Rajasingam et al 1 assessed the efficacy of pre-exposure prophylaxis of hydroxychloroquine to prevent covid-19 in high risk healthcare workers exposed to covid 19 patients. It was done throughout US and a province of Canada. A total of 1483 healthcare workers were recruited and assigned to one of the three groups -HCQ 400mg once weekly or twice weekly or placebo for 12 weeks. The baseline characteristics were comparable including the risk of exposure. 91% were involved for more than 14 hours of direct contact with patient per week and 79% performed aerosol-generating procedures. The primary endpoint was Covid-19–free survival time by laboratory-confirmed or probable compatible illness. The incidence of Covid-19 was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly HCQ compared with 0.38 events per person-year with placebo. For once weekly HCQ prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18) and for twice weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Thus, there was no significant difference of covid-19 incidence between the three cohorts. Gastrointestinal side effect was observed to be more in the two intervention arms.

Another randomised, double blind, placebo controlled trial of HCQ pre-exposure prophylaxis at two tertiary urban hospitals in USA done among health-care workers by Benjamin et al 2 showed similar results. There was no significant difference in covid-19 incidence between HCQ 600mg daily arm (66 participants) and size matched placebo for 8 weeks. The study was terminated due to futility. A prospective observational study conducted by Harshithetal3 in AIIMS, India recruiting 334 healthcare workers of which 248 healthcare workers were taking HCQ voluntarily. The odds ratio of developing Covid-19 among HCQ cohort was 0.13 (95% CI 0.02-0.85,p=0.03) which appears to be protective. But the study was limited by its observational nature, short duration of follow up (3-6 weeks) and selection bias.

Summarizing, there is no large benefit observed with pre-exposure prophylaxis of HCQ in health care workers to prevent Covid-19 infection.


  1. Radha Rajasingham et al, Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial - medRxiv 2020.09.18.20197327; doi:
  2. JAMA Intern Med. 2020 Sep 30. doi: 10.1001/jamainternmed.2020.6319. Epub ahead of print. PMID: 33001138.
  3. Kadnur, Harshith B. et al, Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 Among Healthcare Workers: Initial Experience from India (6/3/2020).