(FIT is republishing this article in the light of ICMR’s announcement advising against the indiscriminate use of convalescent plasma therapy for COVID-19 treatment.)
On a daily basis, one gets at least two to three messages of desperate family members searching for a plasma donor for their loved ones battling COVID-19. Several patients, once recovered, have set up lists to help others, connecting donors to those in need. Delhi set up a plasma bank in June to cater to the increasing demand of COVID-19 patients, with several states following the example.
In June, the Union Health Ministry, in their clinical guidelines to treat COVID-19, had included off-label use of plasma therapy as a treatment option for moderate to severe patients.
But through it all, the question that has repeatedly been ignored is this - is plasma therapy effective in treating COVID-19?
Despite mounting evidence of little or no benefit, including a study by Indian Council of Medical Research itself, the demand for plasma has not ceased.
All this may finally change now. ICMR director-general Dr Balram Bhargava said in a press conference that the government will move to remove plasma therapy from its clinical guidelines. He said, "the largest trial on plasma therapy was conducted in India, 434 patients in 39 hospitals... This paper has been accepted in the British Medical Journal and will appear soon," adding,
“We have had discussions with the Task Force and we are discussing further with the joint monitoring group that this (Plasma Therapy) may be deleted from the national guidelines.”Dr Balram Bhargava, Director-General, ICMR
What is Plasma Therapy? Why Did it Become Such a Sought After Treatment?
In India, the treatment first made news in mid-April when a patient in Delhi received experimental plasma therapy and was weaned off from ventilator support.
Delhi’s Max Hospital gave a 49-year-old male COVID-19 patient plasma treatment on compassionate grounds.
Convalescent plasma treatment is essentially an experimental procedure. Human bodies are evolved to protect themselves against disease by producing antibodies.
- First, a virus or pathogen attacks us.
- In defence, our immune systems gear up to fight by producing antibodies.
- If we can produce enough antibodies, the virus is defeated and all is well - we can be cured of the disease.
In the experimental treatment, antibodies from the blood of patients who have recovered from coronavirus are given to those battling the virus in the hope that it will produce an immune response. You can read more about the process here.
The concept of plasma treatment was not new. In fact, versions of this have existed to treat the Spanish Flu of 1918 to another coronavirus’ like SARS in 2003 and MERS in 2012, according to a study in The Lancet.
At the time, Max Hospital’s Medical Director, Dr Sandeep Budhiraja was cautious not to attribute the recovery to plasma treatment alone. "We are delighted that the therapy worked well in his case, opening a new treatment opportunity during these challenging times. But it is important that we also understand that Plasma Therapy is no magic bullet." He added,
“During the patient’s treatment at Max Hospital, Saket, other standard treatment protocols were followed and we can say that Plasma Therapy could have worked as a Catalyst in speeding up his recovery.”
Earlier that month, the Indian Council of Medical Research (ICMR) sought participation in a randomised controlled study to assess the safety and efficacy of convalescent plasma to limit complications associated with coronavirus. ICMR also asked to participate in a study on therapeutic plasma exchange in improving the clinical status of COVID-19 patients. Seeing a growing demand for the therapy, ICMR also issued a clarification saying the treatment remained experimental.
However, by June, 2020, the Health Ministry, in its COVID Clinical Management Protocols, had approved the "off label" used of convalescent plasma therapy for patients with moderate disease who are not improving (oxygen requirement is progressively increasing) despite use of steroids.
The demand for plasma skyrocketed.
But in first week August, an interim analysis of a randomised controlled trial on convalescent plasma therapy done at AIIMS, Delhi, had found that the treatment does not reduce the risk of death in COVID-19 patients.
On August 24, the US Food and Drug Administration (FDA) issued an emergency approval for plasma therapy as COVID-19 treatment, a week after putting the treatment on hold. The US President Donald Trump has been pushing for approvals, often overriding the advice of medical experts.
Speaking to FIT at the time, experts called out the lack of evidence.
“The theoretical benefit of plasma therapy is in helping boost immunity if not enough is developed in the patient. But, the problem with COVID-19 is not of an inadequate immune response, but in severe patients, the immune response goes haywire.”Dr Sumit Ray, Senior consultant of Critical Care Medicine, Holy Family Hospital
Our immune system works in complicated ways, and the issue with COVID is that it is causing patients to have a disregulated immune response rather than no immune response at all.
“A study from the Netherlands showed that 76 per cent of COVID-19 patients already had antibodies, so what is the point of giving more antibodies through plasma therapy?” asked Dr Ray. “The problem with COVID is not antibodies but a messed up immune response.”
At Worst, Plasma Therapy May Harm Patients
One of the oft-repeated lines about plasma therapy is that it has been used in other diseases and therefore is safe. “But all diseases are not the same,” says Dr Ray. “Here you are giving plasma (which increases clotting) for a disease which is procoagulant or prone to causing clots.”
Dr Neeraj Nischal, associate Professor in the department of medicine at AIIMS, in a quote to PTI, had said, "This therapy also carries risks such as inadvertent transfer of blood-borne infections and reactions to serum constituents, including immunological reactions such as serum sickness, that may worsen the clinical condition."
'Does not help in reducing deaths, prevent disease progression'
Finally, in September, a multicentric study by the Indian Council of Medical Research (ICMR) revealed that the use of convalescent plasma therapy in COVID-19 patients does not help in reducing deaths or preventing disease progression.
The open-label, parallel-arm randomized controlled trial, called PLACID, was conducted in 39 hospitals across India from April 22 to July 14. A total of 464 moderately ill hospitalised patients with COVID-19 were enrolled, of whom 235 were given convalescent plasma along with best of standard care while 229 received only standard care.
"Composite primary outcome was achieved in 44 (18.7 per cent) participants in the intervention arm and 41 (17.9 per cent) in the control arm. Mortality was documented in 34 (13.6 per cent) and 31 (14.6 per cent) participants in intervention and control arm, respectively," the study mentioned.
The study authors also called out the questionable practices such as calls for donors on social media, and the sale of plasma on the black market with exorbitant price tags in India.
Yet, the therapy continued to remain a part of India's clinical protocols to treat COVID-19 and there was no reduction in demand.
If and when the treatment is finally removed from the list, questions will remain on how, despite being an experimental treatment, its use was normalised across hospitals and by governments.
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