by Dr. Muneer Mammi Kutty, Rejesh Bose. K and Abhijith. N. P
Image courtesy: Wikicommons
COVID 19 is wreaking havoc across the world with close to 3.5 million people infected and close to 250,000 deaths as of 3rd May 2020. At the same time, the number of cases in India has crossed 40,000 with 1300 deaths. Researchers and scientists the world over are scrambling to find a possible treatment for the disease and it seems that a vaccine for the disease won’t be available till at least another year. It is in this scenario, that plasma therapy has emerged as a strong contender for treating COVID 19 patients across the world.
What is Plasma?
Blood has four components; Plasma, Red Blood Cells (RBCs), White Blood Cells (WBCs) and Platelets. Plasma constitutes 55% of the total volume and is the liquid component of the blood. It is a mix of water, sugar, fat, proteins and salts. Along with this, the plasma also contains important components like antibodies, clotting factors, albumin and fibrinogen. The main role of plasma is to transport blood cells throughout the body along with nutrients, waste products, antibodies, clotting proteins, hormones and other proteins.
Plasma Therapy: The Basics
The basis for plasma therapy for COVID-19 is the idea of transferring immunity from a healthy to a sick person using convalescent plasma, which refers to the plasma collected from individuals who have recovered from COVID-19. In this therapy, the blood drawn from a COVID-19 recovered individual is separated into serum and screened for virus-neutralizing antibodies, through antibody titre test. First, the swab test must be negative, and the potential donor has to be declared as cured. The plasma is also screened for other diseases like HIV/AIDS, Hepatitis-B, etc. Then, the healthcare provider separates the vital components from the plasma and these parts can be then concentrated into various products. The plasma donors are hooked up to a small device that removes plasma while simultaneously returning red blood cells to their bodies. Unlike regular blood donation in which donors have to wait for red blood cells to replenish between donations, plasma can be donated more frequently. The process is named as plasmapheresis. The antibodies from recovered patients will be used to treat other infected people.
The history of the use of Plasma Therapy:
The use of convalescent plasma as a treatment for infections is not new. It’s use in epidemics dates as far back as Spanish Flu pandemic in 1918. It was also used as a mode of treatment during Hong Kong flu in 1950s, Severe Acute Respiratory Syndrome (SARS) in 2003, Middle East Respiratory Syndrome (MERS) in 2008 and Swine Flu pandemic in 2009-10. The procedure was widely used during the Ebola crisis in West Africa in 2018. In a study conducted in Hong Kong in 2003, 80 patients with severe symptoms of SARS were administered with convalescent plasma and a high rate of recovery was observed in these patients. A meta-analysis from 32 studies of SARS coronavirus infection and severe influenza showed a statistically significant reduction in mortality following convalescent plasma therapy, compared with placebo or no therapy.
Plasma therapy in COVID 19:
Global experiences: Many countries have started experimenting with Plasma therapy in the absence of a credible treatment option. In China, where the disease was first reported, several small scale clinical trials were conducted to evaluate the effectiveness of plasma therapy. In a study conducted in Wuhan between 23 January 2020 and 19 February 2020 in three participating hospitals wherein 10 critically ill patients with COVID-19 were administered Convalescent Plasma (CP). Out of these 10 patients, three were discharged and seven patients showed significant improvement. A similar study with the same number of patients done in Shenzhen also gave satisfactory outcomes from the therapy. In the UK, the National Health Services (NHS) has started clinical trials for the treatment, while in the US, there is an increased demand for plasma therapy and many hospitals have started clinical trials with approval from the US Food and Drug Administration (FDA).
Use of CP therapy in India: The Drug Controller General of India (DCGI) gave the go ahead to Indian Council of Medical Research (ICMR) to conduct clinical trials on CP therapy on 17 April 2020. ICMR received applications from 99 institutions willing to take part in the trials. However, the apex body on medical research in India has maintained the view that it does not recommend CP therapy as an approved form of treatment and has stated that it has not given any clearance for CP as an approved form of treatment. Nevertheless, many states are now advocating for the use of CP for the treatment of severe and critical cases of COVID-19. Delhi was one of the first states to try this mode of treatment in one of the private hospitals in the state. Gujarat too has started clinical trials and many other states including Maharashtra and Tamil Nadu are set to follow.
Difficulties in getting a donor: Aged individuals and people with comorbidities cannot be considered as suitable donors. The donation of plasma is completely voluntary and there are cultural inhibitions to donate blood and blood products. Also, many patients who are debilitated by the disease will not have the mental disposition to donate plasma.
Risk of allergies and blood borne diseases: There is an increased risk of getting allergies and blood borne diseases through plasma transfer if there is no proper screening.
Absence of proper evidence: There are only very few studies that have been done on the effectiveness of CP therapy in COVID-19. The existing studies and clinical trials are mostly from China, where the sample sizes were far too small to be considered as representative. The studies done on the use of CP therapy in other similar infections are also less. Most of what we have to know about the usefulness of this treatment method is anecdotal and cannot be taken as evidence.
Lack of regulatory approval: CP therapy is not recognised as a prescribed form of treatment anywhere in the world. The treatment is done on a trial basis with prior approval and consent from respective regulatory bodies. In India, while many states have expressed their intention to use this treatment for severe and critically ill COVID-19 patients, the ICMR has been categorical in stating that this is not an approved form of treatment. This dichotomy between ICMR and states have, however, created confusion regarding the adoption of CP therapy for COVID-19.
Preliminary analysis suggests that CP is a promising mode of treatment for COVID-19 and it is understandable that the increased clamour for the use of convalescent plasma therapy for the treatment of COVID-19 stems from the lack of any credible options. However, healthcare providers and the governments should be cautious in adopting it on a large scale. We should give more emphasis in generating more evidence and formulating appropriate guidelines for usage of plasma therapy.
Dr Kutty is a Public health practitioner, Mr. Bose is India Project Coordinator, Nexleaf Analytics and Mr. Abhijith is Project Manager at Innovators in Health, Bihar (Samastipur). The views expressed in the article are personal to the authors.