Plasma therapy does not help reduce COVID-19 deaths, finds ICMR study

Convalescent plasma, which can neutralise antibodies and immunomodulators in the fight against viral diseases, does not help in reduction of mortality or progression to severe COVID-19, a study conducted by Indian Council of Medical Research has found. The study has been published by medRxiv and has not been peer reviewed. This means that they are preliminary reports.

It was Phase II of the randomised controlled trial in which 39 public and private hospitals across 14 states in 25 cities participated between April 22 and July 14. Of the 464 participants, 235 were in the intervention arm and 229 in the control arm. Two doses of 200 ml plasma were transfused 24 hours apart in the intervention arm. Those in the control arm were given ‘best standard care’ without the plasma.

In a clinical trial, participants who are not given the experimental intervention being studied are in the control arm. The trial was registered with Clinical Trial Registry of India in April.

In plasma therapy, plasma from recovered COVID-19 patients is used to establish antibodies against SARS-CoV-2 virus into the body of the patient to fight it. For several years, convalescent plasma has been used to fight viral diseases such as poliomyelitis, measles, mumps and influenza in the pre-vaccine era and more recently, during the Influenza and Ebola epidemics.

During the trial, 34 patients who were given the plasma died and 31 patients who were in the control arm died. Seventeen patients each in both arms progressed to severe COVID-19. The proportion of patients with shortness of breath and fatigue at day 7 were higher in those who were given plasma, whereas fever and cough resolution were not different in both the groups.

The proportion of patients requiring vasopressor (medicines that constrict (narrow) blood vessels to increase blood pressure) support were not different between the participants in two arms. Among the 38 participants who required invasive ventilation, only two participants survived till 28 days post enrolment in the study.

In the trial participants who received plasma, pain in the local infusion site, chills, nausea, abnormally slow heart action (bradycardia) and dizziness was reported. Fever and tachycardia were reported in three patients each. In three patients, death was most likely related to the plasma transfusion.

The use of plasma as a treatment for COVID-19 has been approved in India, but it has also seen the rise of questionable practices too such as calls for donors on social media and sale of plasma in the black market.

Calls for plasma donors have been seen especially in New Delhi, even though the state government has set up a plasma bank at the Institute of Liver and Biliary Sciences in South-West Delhi’s Vasant Kunj. Delhi Chief Minister Arvind Kejriwal had insisted even in August that the therapy had proven to be helpful in the recovery of the COVID-19 patients in the Capital. He had, however, not released data to accompany this claim.

The study observed that although the use of plasma seemed to improve shortness of breath and fatigue in the first week, this did not translate into reduction in 28-day mortality or progression to severe case of COVID-19 in moderately ill patients.

To understand how plasma therapy is intended to work, it is important to know how the SARS-CoV-2 virus works in the body. Our lungs usually produce cells to counter several viruses, but COVID-19 manages to cheat our system using the ACE2 protein, which is found on the surface of cells. This protein is important to regulate blood pressure. But, when the coronavirus binds to it, it fuses the membranes around the cell and the virus together, allowing the virus’s RNA to enter the cell. When this happens, the virus takes over the host cell’s protein-making machinery and it converts the hosts RNA into copies of the virus’s RNA. It then proliferates and infects healthier cells. The virus’s RNA also prevents the host cell from sending signals to our immune system that it is under attack.

When our immune system realises it has been attacked, in some cases, it needs help to fight the virus. This help comes from another immune system (in the form of plasma), which has already foiled the virus.

In our body, RNA and DNA are nucleic acids, but RNA carries the viral genetic information. It plays an important role in regulating cellular processes – from cell division, differentiation and growth to cell aging and death.

The ICMR study has come a few weeks after the US Food and Drug Control Administration refused to authorise the use of blood plasma to treat COVID-19 patients until more data about the treatment would be reviewed.