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Explained: The plasma therapy debate

India's largest ever trial has found convalescent plasma therapy ineffective in Covid-19. ICMR is cautious about the option, some states still push it. In what circumstances do experts recommend this therapy?

Blood bank MaharashtraBlood donations have dipped again in February, prompting the State Blood Transfusion Council (SBTC) to write a fresh appeal to all 373 blood banks in Maharashtra to renew their efforts in holding blood donation camps(Express Photo: Tashi Tobgyal)

Recently published findings on convalescent plasma therapy on Covid-19 patients have triggered a debate over its efficacy. After the country’s largest such trial, known by the acronym PLACID, found that convalescent plasma was ineffective in arresting Covid-19, the Indian Council of Medical Research (ICMR) has been considering dropping this option from the national guidelines. However, in several states including most-affected Maharashtra and Delhi, health authorities continue to push the option while those running plasma blood banks promote it with anecdotal accounts on social media.

What is plasma therapy?

Plasma is the liquid part of the blood. Convalescent plasma, extracted from the blood of patients recovering from an infection, is a source of antibodies against the infection. The therapy involves using their plasma to help others recover. For Covid-19, this has been one of the treatment options. The donor would have to be a documented case of Covid-19 and healthy for 28 days since the last symptoms.

What has happened to spark the debate?

An ICMR study has found convalescent plasma was not associated with a reduction in progression to severe Covid-19 or all-cause mortality. The results of the PLACID trial at multiple centres, first out on a pre-print server in September, were published in the peer-reviewed British Medical Journal on October 22.

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At a recent media briefing, ICMR Director General Dr Balram Bhargava had said they were contemplating deleting convalescent plasma as a definitive therapy from the national guidelines for Covid-19 treatment.

Maharashtra State Reserve Police Force personnel donate plasma at a plasma donation drive at Sassoon hospital in Pune. (Express Photo: Arul Horizon)

What are the trial findings?

While use of convalescent plasma seemed to improve resolution of shortness of breath and fatigue in patients with moderate Covid-19, this did not translate into a reduction in 28-day mortality or progression to severe disease.

PLACID was a randomised controlled trial in 39 hospitals spread across 14 states and Union Territories and representing 25 cities. It covered 464 adults admitted to hospital (screened April 22 to July 14) with confirmed moderate Covid-19, of whom 235 were assigned to convalescent plasma therapy while 229 were randomised to receive the best standard of care. The group of 235 received two doses of 200 ml convalescent plasma, 24 hours apart.


Progression to severe disease or death at 28 days after enrolment occurred in 44 (19%) of the participants in the intervention arm as compared to 41 (18%) in the control arm . A higher proportion of patients in the intervention arm showed resolution of shortness of breath and fatigue at day 7, whereas resolution of fever and cough did not differ between the two arm. “These are clinically meaningful results,” said Dr Aparna Mukherjee, Principal Investigator of the PLACID trial.

Have there been such results elsewhere?

In China, a controlled trial of 103 patients with severe Covid-19 reported no effect of convalescent plasma treatment in terms of time to clinical improvement. In the Netherlands, the ConCOVID trial, prematurely terminated after 86 patients had been enrolled, could not find any effect on mortality at 60 days, hospital stay, or disease severity at 15 days.

So, who all are still pushing convalescent plasma therapy?


Delhi Health Minister Satyendra Jain has said convalescent plasma played a big part in his recovery and many lives have been saved. In Maharashtra, the government has been conducting the Platina trial in severely ill patients. It is the brainchild of the Medical Education Department and CM Uddhav Thackeray.

Dr Mohammed Faizal, state coordinator of the Platina Project, said at least 40% of the trial has been completed. “We should be able to complete the trial in another three months. We have recruited 132 patients and the total target is 472,” Dr Faizal said.

Officials said that there is no order or letter from ICMR regarding stopping use of convalescent plasma. “However, ours is a scientific research trial and irrespective of the PLACID Trial findings, the PLATINA trial will continue,” Dr Faizal said. 📣 Follow Express Explained on Telegram

A health worker collects blood samples at a local health centre for Covid-19 in New Delhi. (Express Photo: Praveen Khanna)

What happens if ICMR does remove the therapy from its guidelines?

The ICMR has been cautious because of the trial findings. Experts said, however, that guidelines are not necessarily binding and it is too early to dismiss convalescent plasma therapy.


But there are other issues. The authorisation of convalescent plasma as treatment for Covid-19 in India has led to questionable practices such as calls for donors on social media, and the sale of convalescent plasma on the black market. Although convalescent plasma is a safe form of treatment when transfused in accordance to the regulations, it involves resource-intensive processes such as plasmapheresis, plasma storage, and measurement of neutralising antibodies. A limited number of institutes in India have the capacity to undertake these procedures in a quality-assured manner, the BMJ paper said.

What is the way forward, then?


This is a new virus, and around the world evidence is still emerging on the best therapeutic options. For example, remdesivir has been sanctioned as a drug of choice by the US drug regulator, while the World Health Organization’s Solidarity Trial has found it had little or no effect on 28-day Covid mortality. And experts said use of convalescent therapy has saved some lives but concerns have been raised by the PLACID trial.

Dr Shashank Joshi, member of the Maharashtra task force on Covid-19 and Dean, College of Physicians, said that much before the evidence from trials, the task force had introduced some safeguards to check indiscriminate use of drugs such as remdesivir. “Covid care is individualised care. Use of the right drugs in the right patient does work. Some of the therapies can be continued on compassionate grounds,” Dr Joshi said. He said there were limitations in the Solidarity trial — it was not placebo controlled. While results of the Platina trial are awaited, Dr Joshi said the results of one or two trials are not going to change the outcome of a recommendation.


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Elizabeth Pathak, president, Women’s Institute for Independent Social Enquiry, who has written in the BMJ on the trial findings, said: “The potential harms of the non-immune components of convalescent plasma should be rigorously investigated, only donor plasma with detectable titers of neutralizing antibodies should be given to trial participants, to ensure that the potential for benefit exists for all intervention arm patients.”

First published on: 27-10-2020 at 03:44 IST
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