Low dose hydroxychloroquine prophylaxis for COVID-19 – a prospective study

  1. RE-HCP2 COVID study group
  2. Mayank Agarwal
  3. Rajat Ranka
  4. Prasan Kumar Panda
  5. Ajay Kumar
  6. Gaurav Chikara
  7. Suresh K Sharma
  8. Rizu Negi
  9. Ramanuj Samanta
  10. Rohit Walia
  11. Yogesh Arvind Bahurupi
  12. Sarama Saha
  13. Minakshi Dhar
  14. Prakhar Sharma
  15. Arvind Kumar Gupta
  16. UB Mishra
  17. Manoj Kumar Gupta
  18. Ravi Kant

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Abstract

Background

Since the outbreak of COVID-19 pandemic, the world began a frantic search for possible prophylactic options. While trials on hydroxychloroquine (HCQ) prophylaxis are ongoing, concrete evidence is lacking. The study aimed to determine the relative efficacy of various doses of oral HCQ in prophylaxis and mitigating the severity of COVID-19 in healthcare workers.

Methods

This was a prospective cohort with four arms (high, medium, low dose, and control) of HCQ prophylaxis, used by healthcare workers at a tertiary care center in India. Participants were grouped as per their opting for any one arm on a voluntary basis as per institute policy under the Government guidance. The outcomes studied were COVID-19 positivity by RT-PCR and its severity assessed by WHO COVID-19 severity scale.

Results

Total 486 participants were enrolled, of which 29 (6%) opted for low dose, 2 (<1%) medium dose, and none for high dose HCQ while 455 (93.6%) were in the control arm. Of the 164 participants who underwent RT-PCR, 96 (58.2%) tested positive. Out of these 96 positive cases, the majority of them (79 of 96 [82.3%]) were ambulatory and were managed conservatively at home. Only 17.7% (17 of 96) participants, all of them from the control group, required hospitalization with the mild-moderate disease. None of the participants had severe disease, COVID-related complications, ICU stay, or death. The difference in the outcome assessed amongst the various arms was statistically insignificant (p value >0.05).

Conclusion

This single-center study demonstrated that HCQ prophylaxis in healthcare workers does not cause a significant reduction in COVID-19 as well as mitigating its severity in those infected. At present, most of the trials have not shown any benefit. The debate continues to rage, should HCQ prophylaxis be given to healthcare workers for chemoprophylaxis?

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  1. ScreenIT

    SciScore for 10.1101/2021.09.13.21262971: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIACUC: This study was approved by the Institutional Ethics Committee (IEC) at All India Institute of Medical Sciences, Rishikesh (CTRI/2020/06/025593).
    Consent: Consent was obtained electronically after the participants read the online information sheet regarding the nature and implications of the study.
    Sex as a biological variablenot detected.
    RandomizationThere was no randomization since the decision for drug prophylaxis and dosing was taken by the participants themselves as per available Government guideline and other literatures.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    None of the participants on follow up showed any abnormity in electrocardiogram and fundus examination This study had few limitations. Firstly, the design of the study was a cohort study, just observing the participants taking HCQs or not. The sample size in the intervention arm was very small and we cannot exclude the possibility of a modest prophylactic effect that remained undetected. Moreover, the frequency of exposure to COVID-19 was not quantified and the drug concentrations were not monitored. The cohort comprised mostly of young and healthy healthcare workers. Therefore, the results cannot be generalised for the more vulnerable sections of the population. The study was conducted at a single centre in the North India and therefore, may not be representative of disease prevalence and exposure in other regions. The design of the study was such that the participants got themselves tested as per the clinical need only and as a result, 66 % of the total participants were never tested during the study period. Hence, asymptomatic COVID-19 infections were not accounted for. Drugs like ivermectin and antiretroviral agents have also been tried and tested for the prevention of COVID-19, but head-to-head trials have been lacking. Of these, ivermectin received governmental approval for mass distribution in various states in India.(20) However, as per the available evidence, none of these agents should be used for chemo-prophylaxis outside the context of a clinical trial.(21,22) Eve...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.09.13.21262971v1 on medRxiv