Cool but Misinterpreted HCQ PreP Study

Abella et al. [1] suggests that pre-exposure Hydroxychloroquine prophylaxis might protect a person against COVID-19, but to acquire immunity against it!

Hydroxychloroquine initially accumulates in the lung tissues, then in spleen and liver (according to experiments in animals [2]). SARS-COV-2 usually enters and starts replicating in the upper respiratory tract [3] and then moves down to the lungs, where it causes most damage. Thus, it might be expected that HCQ / HCQ+Zinc prophylaxis would prevent SARS-COV-2 from infecting lungs and the rest of the body, while the immune system response builds up. After that, immunity remains for long time.

The study  confirmed that. All four persons on HCQ who were PCR-positive have also developed IGG antibody. In the same time, they experienced no or very mild symptoms. HCQ prophylaxis is expected to prevent or mitigate illness, not positive test results.

This study has many limitations and is not sufficient to demonstrate this effect, but it is consistent with it. Further studies should be done.

Of note, there was no difference in QTc, despite HCQ accumulation many times exceeding one achieved in a treatment.

Effectiveness of HCQ Prophylaxis is not Challenged

Of course, the study does not call in question the known effectiveness of HCQ prophylaxis [4]:

  1. HCQ studies conducted on health care workers cannot be blind or placebo controlled. A healthcare worker knows whether s/he received HCQ or placebo. Further, HCWs that receive HCQ are likely to feel themselves more protected and to take more risks of infection.
  2. This study is severely underpowered. There were only 4 PCR positive persons in each arm.
  3. 600 mg of HCQ daily for 8 weeks is not how HCQ prophylaxis is done, and is overdose. Typical prophylaxis regimen is 1,200-2,000 mg over five days to achieve a prophylactic concentration of HCQ metabolites in the tissues, then 400 mg per week to maintain it. Daily 600 mg of HCQ is likely to suppress person’s immunity after 2-3 weeks of such prophylaxis, leaving one less protected against all infections. The authors stressed that they could not always verify what disease the patients had.

[1] Abella BS, Jolkovsky EL, Biney BT, et al. Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial. JAMA Intern Med. Published online September 30, 2020. doi:10.1001/jamainternmed.2020.6319

[2] Browning D.J. (2014) Pharmacology of Chloroquine and Hydroxychloroquine. In: Hydroxychloroquine and Chloroquine Retinopathy. Springer, New York, NY.

[3] Wölfel, R., Corman, V.M., Guggemos, W. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465–469 (2020).

[4] Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, Singh H, Praharaj I, Gangakhedkar RR, Bhargava B, Panda S. Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. Indian J Med Res 2020;151:459-67.