New Delhi: Delhi Health Minister Satyendar Jain, who is recovering from Covid-19, underwent Convalescent Plasma Therapy (CPT) last week — a procedure that the Indian Council of Medical Research (ICMR) still categorises as “experimental”.
Any hospital or doctor using it on a patient can do so expressly for the purpose of a trial and with the approval of the hospital ethics committee.
This is why the word therapy does not appear in ICMR’s 12 April protocol document that called for participation in “Phase II, Open Label, Randomized Controlled Study to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications”.
Jain underwent the procedure at Max Healthcare, Saket. The hospital declined to share the circumstances under which the decision had been taken to administer CPT to him.
CPT is a trial
A randomised controlled study compares the effect of a drug or intervention in patients who get it with those that do not, to assess whether there are any significant benefits of that intervention. This is one of the standard methods of clinical trials.
A phase II trial, which has a large number of participants, happens when the safety and efficacy of a particular therapeutic option have already been established by its use in small groups of patients.
CPT involves transfusion of the blood plasma of a recovered patient into one who is unwell in the hope that the antibodies present in the recovered patient’s blood would transfer some of their “memory” of tackling the disease to the recipient. Plasma is the matrix on which the blood cells float.
CPT has also been used in the past for diseases like Ebola.
According to the ICMR protocol, CPT is to be used in “Hospitalized COVID-19 patients fulfilling the inclusion and exclusion criteria, and admitted for care at COVID-19 management facilities in India”. The inclusion and exclusion criteria would be determined by investigators as per the design of the study.
The purpose of the ICMR trial, for which it invited participation, is to assess the efficacy of CPT in improving the clinical status of Covid-19 patients and to evaluate the safety of treatment with anti SARS-CoV-2 plasma in the patients.
CPT is based on the concept of passive immunity, dating back to the times when antibodies for diseases like diphtheria were developed in horses and injected into humans.
According to 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.”
T-cells are blood cells that have a crucial role in immunity.
The “matching” of donor and recipient plasma is similar to the matching done for whole blood transfusion. It is based on whether the antibody of a particular blood group is present in the plasma — so blood group A which has antibody b in the plasma, cannot receive plasma from a donor whose blood group is B. But it can receive from a person of blood group A or AB. This is because the b antibody would react with the b antigen present in the red cells of the B group blood. AB blood group, however, has neither A nor B antibodies, so for the purposes of plasma therapy, it is the universal donor.
A study in the journal Viruses suggests that CPT may only work if the donor has recently recovered from a SARS-CoV2 infection.
The US Food and Drug Administration has also issued guidance on the use of convalescent plasma as an “investigational” product against Covid-19.
In an April study in US-based Proceedings of the National Academy of Sciences, Chinese researchers reported about a pilot CP 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. 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.” They reported no adverse events.