New Delhi: It was exactly seven months ago that Dr Balram Bhargava, director general of the Indian Council of Medical Research (ICMR) first announced that India is planning to remove plasma therapy as a Covid-19 treatment option. An ICMR study found that infusing blood plasma from a recovered patient showed no significant benefits on a patient’s eventual outcome.
The decision was finally announced late Monday night, when infusion of convalescent plasma was removed as an “off-label” treatment option.
In the interim, several other studies — the latest published in The Lancet medical journal — came to the same conclusion about the treatment, but Indians continued to run from pillar to post trying to procure plasma from recovered Covid patients for their loved ones. Celebrities and FM channels promoted plasma donation as an act of philanthropy and hapless families paid substantial sums of money for it in private hospitals, even though there was no proof that it worked.
The moot question is what took India seven months to act on research findings of its own apex medical research body, published in The BMJ (originally called The British Medical Journal) and change its clinical management guidelines?
While the ICMR study has been criticised for its inability to assay neutralising antibodies — those that specifically attack the SARS-CoV-2’s spike protein and neutralise it — a plethora of other studies since then have come to the same conclusion.
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What is plasma therapy?
Plasma is the matrix in which blood cells float. Antibodies — crucial cogs in the body’s immunity wheel — are found inside it.
Plasma therapy or the introduction of antibodies from one person who has successfully fought off the virus into another, in a bid to kickstart the latter’s immune system, is a practical application of the concept known as passive immunity.
According to the Textbook of Medical Physiology by Guyton and Hall, “Temporary immunity can be achieved in a person without injecting any antigen. This is done by infusing antibodies, activated T cells (blood cells that have a crucial role in immunity) or both obtained from the blood of someone else or from some other animal that has been actively immunised against these antigens. These antibodies last for two-three weeks and during that time, the person is protected against the invading disease.
“Activated T cells last for a few weeks if transfused from another person and for a few hours to a few days if transfused from an animal. Such transfusion of antibodies or lymphocytes to confer immunity is called passive immunity.”
What did the studies find?
ICMR’s PLACID trial, published in October 2020, came to the conclusion that “convalescent plasma was not associated with a reduction in progression to severe Covid-19 or all cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity. A priori measurement of neutralising antibody titres in donors and participants might further clarify the role of convalescent plasma in the management of Covid-19”.
This finding was the basis of Dr Bhargava’s statement last October that plasma therapy is all set to be removed from the clinical management guidelines. Replying to a question from ThePrint at a press conference on 20 October, he had said: “We have discussed this in the national task force and are discussing further now with the joint monitoring group that this (plasma therapy) may be deleted from the national guidelines. That is the discussions ongoing and more or less we are reaching towards that.”
Most recently, the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial conducted by the University of Oxford found that the use of plasma therapy on hospitalised Covid patients does not improve survival rate or any other pre-specified clinical outcomes. The trial, whose findings were published in The Lancet Friday, is assessing several possible treatments in patients hospitalised with Covid in the UK.
Another study in Argentina, whose findings were published in the New England Journal of Medicine, also came to the same conclusion.
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Why did India continue to use plasma?
For an unproven clinical option, plasma therapy has had a dream run in India. It has been administered to several ministers, including Union Minister Shripad Naik in Goa and Delhi government ministers Satyendra Jain and Manish Sisodia. All of them recovered from Covid-19.
This run continued despite the fact that a month after Bhargava’s statement about removing plasma therapy from the clinical management guidelines, ICMR issued an advisory that indiscriminate use of the therapy is not advisable, and specified the minimum neutralising antibody concentration in plasma that is necessary before transfusion.
Why did ICMR change its stand, or at least soften its opposition to convalescent plasma therapy? There are various theories doing the rounds — such as while Bhargava was not convinced about the viability of the treatment, others from his parent institution, AIIMS New Delhi, were in doubt about the findings of ICMR’s PLACID trial.
A senior doctor at a government hospital in the capital, speaking on the condition of anonymity, said: “It is only in India that we would choose to ignore the findings of the country’s premier scientific organisation, published in The BMJ, based on some ‘perceptions’ others may have. Why did we wait for an international study to remove plasma therapy when our own Indian study found it to have a dubious value?”
‘Some people don’t understand its purpose’
But even now, not everyone is convinced about the decision to do away with plasma therapy as a treatment option.
Dr Ashok Rattan, a microbiologist who retired from AIIMS as an additional professor and currently works for Pathkind Labs, compared the decision to the proverbial ‘throwing the baby out with the bathwater’.
“Some people do not really understand the purpose of convalescent plasma therapy. It has been established as a therapy for the last hundred years; it is used in diphtheria, tetanus, gas gangrene… Even with (former US) President Trump, you saw that monoclonal antibodies worked,” Rattan told ThePrint.
“The point in convalescent plasma therapy is that the plasma has to have a high titre (concentration) of neutralising antibodies, which the ICMR did not check in its study, and it has to be given early in the disease — in the first 72 hours after infection. The problem here also is the fact that most people were donating plasma have actually had mild illness, so antibody titre is not very high,” Rattan explained.
“Instead of convalescent plasma, we should have tried transfusing high-titre plasma obtained from healthy individuals who have been vaccinated. Scientists are using this to see if variants escape or not in vitrio,” he added.
(Edited by Shreyas Sharma)
Also read: What’s on our minds in peak pandemic? ‘Oxygen’, ‘plasma’ and ‘remdesivir’, says Google