Explained: How plasma therapy works, what India plans

As govt prepares to frame a protocol for convalescent plasma therapy, a look at the science behind injecting a recovered patient’s plasma into a serious patient.

Donated blood and plasma samples at a hospital in Germany. Reuters

Even as trials are undertaken across the world, some independently and at least one under the aegis of the World Health Organization (WHO Solidarity Trial) to look for therapeutics to fight the novel coronavirus disease (COVID-19), India is all set to try out a therapy that involves attempting to jump-start the immunity of a serious patient by infusing some of the blood plasma of a person who has already recovered from the disease. COVID-19 LIVE updates

This is called convalescent plasma therapy and has in the past been used in many other diseases.

Explained: What is convalescent plasma therapy?

Convalescent plasma therapy, which was recently allowed by the US Food and Drug Administration (FDA) for investigation purposes – clinical trials etc in a regulated way – involves transfusion of the blood plasma of a recovered patient into another patient. Plasma is the matrix on which the blood cells float. It also houses crucial components of immunity known as antibodies. Antibodies are the immediate warriors who fight an invading pathogen – an antigen – to defeat it. Once that is done, some blood cells function as memory cells so that they can identify and defeat the same enemy if and when it invades again by quickly producing the same antibodies.

Source: Johns Hopkins University, updated at 11:00 pm on April 10

Convalescent plasma therapy banks on the age-old concept of passive immunity when antibodies for some diseases, such as diphtheria, were developed in horses and injected into humans. Active immunity is what is achieved by introducing an attenuated pathogen (such as the BCG vaccine) into the body to generate an immune response. The other kind of immunity is passive immunity.

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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 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.”

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T-cells are blood cells that have a crucial role in immunity.

Convalescent plasma therapy: What is India planning to do?

The country’s apex medical research organisation, Indian Council of Medical Research (ICMR), is framing a protocol for infusing blood plasma from people who have recovered from COVID-19 into serious patients.

This will only be done by way of a clinical trial, in patients who are in a severe condition, or on ventilator. “We are in the final stages of making a protocol for convalescent plasma therapy and after that we will need approval from the drug controller general of India. This is not for use in all patients. It will be done on trial basis. Abroad it has been found successful in limited trials. Here we will do it only on patients on ventilator or severe patients,” Dr Manoj Murhekar, Director, ICMR-National Institute of Epidemiology, said on Thursday.

Union Health Ministry update as of 11 pm, April 10. Some states may have reported higher numbers. Only states with the most cases are listed above.

In Kerala, Dr Anoop Kumar, member of the state-constituted expert committee for advising the government on COVID-19, said he had spoken to some who had recovered from COVID-19 and they are ready to be part of the plasma therapy trial. The state too would need clearance from the national drug controller before going ahead with such a trial.

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Though Kerala has expressed anxiety about the availability of kits for checking the antibody level in the plasma of a recovered person, the transfusion process itself is not very complicated. It requires separation of the plasma from whole blood, through a machine and then transfusion. The kit to check antibody level, though, is not available in India and has to be brought from Germany.

What is the position of other countries on such therapy?

The United States FDA said on April 8: “FDA has issued guidance to provide recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency… Because COVID-19 convalescent plasma has not yet been approved for use by FDA, it is regulated as an investigational product.”

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In a study last last month in the Proceedings of the National Academy of Sciences of the United States of America, Chinese researchers reported about a pilot convalescent plasma therapy in 10 patients. They reported: “all symptoms in the 10 patients, especially fever, cough, shortness of breath, and chest pain, disappeared or largely improved within 1 d to 3 d upon CP transfusion.

Maharashtra Medical Education Department update at 10 am on April 10. The last count will not match that of the Union Ministry’s evening update

Prior to CP treatment, three patients received mechanical ventilation, three received high-flow nasal cannula oxygenation, and two received conventional low-flow nasal cannula oxygenation. After treatment with CP, two patients were weaned from mechanical ventilation to high-flow nasal cannula, and one patient discontinued high-flow nasal cannula. Besides, in one patient treated with conventional nasal cannula oxygenation, continuous oxygenation was shifted to intermittent oxygenation.” Most importantly, they reported, no adverse effects were observed.

When has convalescent plasma therapy been tried before?

It has been tried for several diseases, most recently for Ebola. The WHO had issued a detailed guidance document for its use in the wake of the Ebola outbreak, to be used as an “empirical treatment modality”. “While there is no proven treatment available for Ebola virus disease (EVD), whole blood collected from patients in the convalescent phase of infection has been used as an empirical treatment with promising results in a small group of EVD cases.

During the current ongoing EVD outbreak, whole blood and plasma collected from EVD recovered patients has been prioritized for investigation, as one of the treatment modalities. The concept that this treatment could be efficacious is biologically plausible, as convalescent plasma has been used successfully for the treatment of a variety of infectious agents,” reads the WHO document.

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