Need scientific consensus on Covid-19 therapeutic lines
Given Covid-19’s complexity, it has proven difficult for any therapeutic intervention to emerge as canon. Sets of informed opinions, backed by rigorous academic studies, have even clashed. A letter to the Union government’s principal scientific advisor K Vijay Raghavan, signed by vaccine-research stalwart Dr Gagandeep Kang and eminent virologist Dr Shahid Jameel, along with 16 other experts, flags the “irrational and non-scientific use” of convalescent plasma (CP); the experts say that there is a lack of evidence of its efficacy. To the contrary, it might be causing harm—early findings from a recent study suggest CP helped nurture the evolution of the virus towards greater immune-escape. The experts draw attention to the ICMR’s PLACID trial last year which concluded that CP therapy “was not associated with a reduction in progression to severe covid-19 or mortality.”
Though, importantly, it had also stated that the trial could not determine if the plasma used contained neutralising antibodies, the most effective antibodies against the pathogen, since the country lacked the capacity to do this at the time; indeed, this had been the focal point of the critique of the trial. While multi-center efficacy assessments conducted by Chinese and Iranian scientists and a trial at Mount Sinai Hospital in New York—all three published in top academic journals—discuss positive clinical outcomes, these have limitations ranging from small sample size to non-randomisation.
With waters thus muddied, should Indian health authorities then look at the Oxford University’s RECOVERY randomised controlled trial involving 11,588 patients? This trial, cited by Kang et al, identified high counts of antibodies, including neutralising antibodies, in the plasma administered. It reported that the therapy “did not improve survival or other prespecified clinical outcomes.” While it is awaiting peer review, its observations could perhaps help the government nuance its stance on the intervention—right now, the ICMR’s April 22 clinical guidelines recommend “off-label” use of CP only in case of early moderate disease and availability of high-titre donor plasma. The RECOVERY trial also makes important observations on age of the recipient, and the link between efficacy and likelihood of ‘match’ between the antibodies in the donor plasma and the variant(s) of the virus in the recipient. The government’s experts need to carefully study these to calibrate the policy stance on the therapy.
Similarly, while the WHO has cautioned against its use in Covid-19—even ivermectin-maker Merck flags lack of efficacy-data—a new, peer-reviewed meta-study published in the American Journal of Therapeutics strongly argues for wide use of the drug. Calls for the government to let science inform its Covid-policy are getting get louder, but the need for scientific consensus is also more pronounced now. Be it ivermectin or CP therapy, the government will perhaps need to conduct large trials to see what works, in the absence of a consensus. At the same time, the need is also for the global scientific community to work on meta-analyses of studies/trials to see if a common opinion can emerge.