Covid prevention: Is HCQ better as a prophylactic?

The medicine can now be given to asymptomatic healthcare workers working in non-Covid hospitals, frontline staff on surveillance duty in containment zones and paramilitary/police personnel who are involved in Covid-19 monitoring.

The Indian Council of Medical Research (ICMR) on Friday expanded the list of people for whom hydroxychloroquine (HCQ) is recommended for prophylactic (preventive) use against Covid-19. It can now be given to asymptomatic healthcare workers working in non-Covid hospitals, frontline staff on surveillance duty in containment zones and paramilitary/police personnel who are involved in Covid-19 monitoring. It had been allowed for asymptomatic healthcare workers working with Covid-19 patients and household contacts of laboratory confirmed cases so far.

The ICMR’s new advisory noted that testing under lab conditions at the National Institute of Virology had shown that HCQ reduced the infectivity of the virus, apart from causing a “log reduction” in copies of the virus’s genetic material.

However, ICMR’s advisory comes against a backdrop of a raft of research finding HCQ ineffective in active Covid-19 cases, indeed, exacerbating adverse outcomes in some cases. Two studies published on May 15 in the journal, BMJ, found that HCQ was of little effect in Covid-19 — a study from France shows that the drug didn’t significantly reduce admission to intensive care or death in Covid-19 patients hospitalised with pneumonia. Eighty-four of 181 such patients were administered HCQ within 48 hours of admission and 97 were given standard care. The researchers found no significant difference between the two groups for transfer to intensive care, death within seven days of admission or onset of acute respiratory distress syndrome within 10 days.

The other study, a randomised clinical trial from China, showed that hospitalised patients with mild-to-moderate Covid-19 who received HCQ didn’t become free of the virus any sooner than those receiving standard care. One-hundred and fifty adults hospitalised with mild or moderate Covid-19 were split into two groups, with one receiving HCQ with standard care while the other received standard care alone. On day 28, both groups had similar Covid-19 rates, with symptom alleviation showing no significant difference; indeed, adverse outcomes were higher for those how had received HCQ.

An increasing body of work on HCQ in Covid-19 treatment seems to suggest that the anti-malarial drug may not have much of an effect on the disease. Despite this, HCQ is included in the Covid-19 management guidelines of many countries, including China and the US.

Findings of a study by US- and Swtizerland-based medical researchers, published on May 22, in The Lancet, would likely give a clearer picture, by the sheer force of the sample size considered in the study. Of the 96,032 Covid-19 patients hospitalised during the study period and meeting the inclusion criteria, 14,888 were divided into different treatment groups: 1,868, receiving chloroquine (CQ), 3,783 receiving chloroquine with a macrolide (any from a class of common antibiotics featuring clarithromycin, erythromycin, azithromycin and fidoxymycin), 3,016 receiving HCQ and 6,221 receiving HCQ with a macrolide.

The remaining 81,144 patients were the control group. After controlling for multiple factors such as age, sex, ethnicity, BMI, co-morbidities, against a mortality of 9.3% in the control group, the HCQ cohort reported a mortality of 18%, HCQ with macrolide 23.8%, CQ 16%, and CQ + macrolide 22.2%. Also, compared with 0.3% of de-novo ventricular arrhythmia in the control group, HCQ cohort reported 6.1%, HCQ + macrolide 8.1%, CQ 4.3% and CQ + macrolide 6.5%.

A study in April conducted at the US Veterans Health Administration medical centres found that Covid-19 patients who took HCQ had a higher likelihood of dying than those who weren’t given the drug — the study was funded by the US National Institutes of Health and the University of Virginia — with 97 who were given HCQ from a group of 368 reporting a 27.8% death rate, while 158 that didn’t take the drug had an 11.4% death rate.

However, US President Donald Trump, who had criticised the Veterans’ Health Administration study as “anti-Trump” shocked the world, saying that he had been on an HCQ regimen as a Covid-19 preventive measure. Researchers are looking into whether HCQ could have a prophylactic effect, with 17 of 53 trials at various stages of recruitment in the US focussing on studying this.

The ICMR advisory mentions the findings of a review of the prophylactic use of HCQ as per the earlier protocol — data pertaining to 1,323 healthcare workers put on the regimen found mild adverse effects such as vomiting (1.5%), low blood sugar (1.7%), cardio-vascular effects (1.9%), abdominal pain (7.3%) and nausea (8.9%). It also talks about a significant relationship between the number of prophylactic doses taken and the frequency of occurrence of SARS CoV-2 infection in symptomatic healthcare workers.

That apart, it notes that another investigation at three central government hospitals in New Delhi reported lower likelihood of contraction of SARS CoV-2 in health workers involved in Covid-19 care who had were on the HCQ prophylactic regimen, though there was a less pronounced effect in healthcare workers caring for a general patient populatio