Unregulated use of plasma therapy for COVID-19 can be harmful, writes expert; can expose patients to serious transfusion-related risks

Editor’s Note: This piece was originally published on 29 April. It is being republished in the light of the first coronavirus patient in Maharashtra to be treated with plasma therapy passing away at Bandra’s Lilavati Hospital. Since the beginning of the COVID-19 crisis, the global scientific community is struggling to find solutions to stop the spread of the contagion and to effectively treat the infection caused by it. As this is a new and evolving crisis and it has taken the world by storm, abundant theories and remedies are floating around, but no definitely proven therapy has emerged. [caption id=“attachment_8263411” align=“alignleft” width=“380”]  Representational image. AP[/caption] While the disease spread is currently being countered with WHO advocated strategies of containment with lockdown, patient identification by testing for infection and quarantine of patients and suspected patients, these strategies will only slow down the spread of the disease but the world will still need treatment and a vaccine for the prevention of infection. Some vaccines are under development and will need months before they hit the market, if at all. In the meantime, the global spread of the infection is killing thousands of people daily and there is a severe need to treat the patients with specific medications and other therapy directed at the virus in addition to standard care. There are a few contender medicines including the malaria drug hydroxychloroquine, an antiviral Remdesivir, and Ivermectin, a drug used for worms and other parasites, but the results are not hugely encouraging and at times conflicting. In this backdrop, plasma therapy is being seen with interest as a cure for COVID-19 patients. What is plasma? Human blood is composed of cells like the red cells that carry oxygen, white cells that fight infection and platelets that stop bleeding from cuts. The watery part contains minerals and many proteins like albumin, factors that make the blood clot, and antibodies which are special proteins produced by the body against infective agents. The serum is the plasma from which the clotting factors have been removed. What is plasma therapy? Plasma transfusion is a very common process done during major surgeries and in patients with bleeding, mainly to provide clotting factors. The main component of interest in plasma therapy and serum therapy for infectious diseases like COVID-19 is the antibodies. The principle applied is that a person who has recovered from the infection would have antibodies directed against the infective agent, in this case, the COVID-19 virus. **Click here for Coronavirus Outbreak LIVE Updates** It is assumed that if injected to a person currently having the disease the antibodies would neutralise the virus, helping in achieving an early cure. Injecting the plasma or serum from patients who have recovered from the disease, called convalescent plasma, may achieve this. Plasma therapy has been used earlier with some success in other infections like in two previous corona viral epidemics SARS-CoV1 and MERS, and also in H1N1 of 2009-10 and Ebola epidemic. Likewise, the animal serum is widely used in the treatment of diseases like tetanus, diphtheria, gas gangrene, botulism, snake and spider bite. How is plasma therapy done for COVID-19? Convalescent plasma transfusion is a relatively easy process. It involves collecting plasma by a process called apheresis or whole blood collection as for blood transfusion followed by separation of the plasma in the laboratory from patients who have recovered from the infection. The donor is tested as for any blood donor and the plasma is then subjected to standard testing as for blood transfusion. In addition, a few more criteria are to be fulfilled which include a positive diagnostic or serological test in the donor and sufficient time has passed since recovery to render the plasma non-infective. If the donor is female then a special class of antibody called HLA antibody should be absent in the plasma. The donated plasma must have sufficient antibodies against COVID-19 to offer treatment value. Which COVID-19 patients can have plasma therapy Currently, India has not framed any guideline for mass use of plasma therapy in COVID-19 patients. The Indian Council of Medical Research (ICMR), the apex medical body in India, is still conducting a trial on the effectiveness of the therapy. A few centres in India have used it but the number of patients treated is few. The USFDA, the apex body in the US regulating food and drugs and medical equipment and therapies, has on its 13 April 2020 recommendations suggested that plasma therapy be used:

1. In registered clinical trials for investigational use
2. expanded access for use in seriously ill patients who are not eligible or are unable to participate in a clinical trial
3. single patient use of an investigational drug in case of a life-threatening situation on the advice of a licensed physician under FDA authorisation. This is like using the medicine on compassionate ground. Random use of the therapy for COVID-19 patients in the absence of patient selection and treatment guidelines formulated by scientific bodies has not been approved in any country. Significantly, the Union health ministry advised against considering plasma therapy as regular therapy for COVID-19 patients and added that it should only be used for research and trials at present.

Why caution is being exercised on using plasma therapy At present plasma therapy for COVID-19 is still under investigation and concrete data on its usefulness is not available. All medical devices and drugs pass through stringent evaluation for safety before allowed to be used as a regular therapy. Plasma transfusion carries a number of risks, some of which are very serious. These include transfusion-related acute lung injury (TRALI) which can cause breathing difficulty/respiratory failure, transfusion-associated circulatory overload (TACO) which can cause heart failure symptoms, allergic reactions or life-threatening anaphylactic shock, risk of infection from other pathogens in the donor’s plasma or acquired during processing, fever, graft vs host disease, hemolysis or breakdown of red blood cells in the recipient etc. Also, we still don’t know exactly at what stage of the illness the patient should be treated, what should exclude a patient from getting this treatment, how much antibody should be present in the plasma to provide the benefit of treatment. Since every medical therapy has to be decided on risk versus benefit ratio, till the time a clear benefit from the therapy against the disease is established and the benefit clearly outscore the risk it can be harmful to the community if allowed for use beyond controlled settings. What the available evidence is for its use Previous studies, though with some flaws in study design, on the use of plasma therapy on H1N1 (Spanish flu), swine flu, SARS-CoV1 has documented positive results. A 2014 Meta-analysis of studies on the use of plasma therapy in influenza and corona viral infections showed a consistent reduction in mortality. Incidence of severe adverse effects has been quite low. This evidence forms the basis of trying plasma therapy in the current pandemic. However, the pool of evidence on the use of plasma on the COVID-19 is quite small, given the time frame of the disease. We will still need to wait for results from investigational trials to know the answer. Is there a chance for plasma in COVID-19? Like many of the options already explored for COVID-19, this is one of the options. It may show modest success, good success or no success. Plasma therapy has always been used in the past and in a variety of conditions but almost always the advent of a vaccine or an antibiotic has pushed plasma therapy to the background. If it proves to be of some success it will be approved for use in regular clinical settings by regulatory and scientific bodies. If approved for use it will definitely buy some time and save a few lives till a vaccine is available or herd immunity is developed. It is a promising solution at the present gloomy situation, but till we have reliable evidence on utility unregulated use is to be avoided, as random use does not contribute meaningfully to the database from which a useful conclusion can be drawn. A lot of studies are going on the world over on its use, and hopefully, we will soon know the answer. The author is a consultant anesthesiologist in a private hospital in Delhi-NCR.