By Dr SUNIL KUMAR KOTA
Since the advent of COVID_19 in December 2019, the novel corona virus has left its foot hold in more than 210 countries across the globe. Rightly so, it was declared as pandemic by World Health Organization in 12th March 2020. Because of persistent mutation and evolution in the viral structure, particular target of the novel corona virus (nCoV) has not been identified against which vaccine or particular treatment can be instituted. Due to the unavailability of the vaccine or medication for this deadly virus, doctors and healthcare professionals across the world are trying their best to treat patients with available possibilities. Till date several drugs are being used with varying results. The list includes antibiotics (Azithromycin), antimalarial (chloroquine), antivirals (Remdesivir, Fapilavir, combination of Lopinavir & Ritonavir) and immunomodulatory agents (Tocilizumab, Sepsivac) etc.
Another one such treatment that’s in focus right now is Convalescent Plasma Therapy. Recently the Indian Council of Medical Research (ICMR) has suggested plasma therapy to be tried in the clinical trial setting in some selected hospitals including AIIMS, New Delhi and has issued relevant guidelines to try this form of treatment to observe its efficacy and safety on patients infected with the nCoV. It is being trialled in several other countries as well like USA, UK, Canada, Italy, Spain, China Turkey etc. However, since this is not the actual treatment for the virus and has not been tested for its efficiency, the ICMR and public health officials have also advised other centres to avoid this mode of treatment. The current article aims to make people aware about some basic facts about this upcoming mode of treatment in form of some questions and answers.
1. What is Convalescent Plasma Therapy?
Ans: We have our own defence system in body called as Immune system. Whenever there is an attack by external pathogens (Bacteria, viruses etc), specific set of white blood cells known as lymphocytes produce antibodies or immunoglobulin specifically against the invading pathogens. These antibodies then curtail the growth of the pathogens ultimately leading to their elimination.
Similarly when a person gets infected with nCoV, he/she produces antibodies which have the ability to act specifically against this virus. These antibodies are present in the body, even after being disease free. The convalescent plasma therapy uses antibodies from the blood of a recovered Covid-19 patient to treat those critically affected by the virus. The therapy can also used to immunise those at a high risk of contracting the virus.
The theory is that the recovered patient’s antibodies, once ingested into somebody under treatment, will begin targeting and fighting specifically the nCoV in the subsequent patients to eliminate the virus. The convalescent plasma therapy is akin to passive immunisation. So briefly in this therapy, blood from recovered patients, which is rich with antibodies, used to treat other sick people.
2. How does Convalescent Plasma Therapy work?
Ans- Once the patient has recovered, they donate their blood so that their antibodies can be used to treat other patients. The donated blood is then checked for the presence of any other disease-causing agents such as Hepatitis B, Hepatitis C, HIV etc. Once deemed safe, the blood is then taken through a process to extract ‘plasma’, the liquid part of the blood that contains antibodies. The antibody-rich plasma, once extracted, is then ingested into the body of a patient under treatment. Via blood the antibodies reach different target tissues and fight the virus there within.
Donating plasma is similar to donating blood. A small device is used on a recovered patient which helps remove plasma from the blood and the red blood cells are sent back to the body. Unlike regular blood donation in which donors have to wait for red blood cells to replenish between donations, plasma can be donated more frequently, as often as twice a week. This procedure takes an hour or two.
For effective therapy a sufficient amount of antibody must be administered. When given to a susceptible person, this antibody will circulate in the blood, reach tissues, and provide protection against infection. Through this therapy, the sick acquires only temporary passive immunization. It lasts only till the time the injected antibodies remain in the bloodstream—usually less than a week. On the other hand, a vaccine, if developed, could provide life-long immunity against the pathogen.
3. Who can be the candidates for Plasma Therapy?
Four categories are identified as potential recipient of plasma therapy
a. A person infected with nCoV and is severe or critically ill
b. Health care workers
c. Family members of the patient infected with nCoV
d. High risk population including elderly, those having diabetes hypertension, chronic lung, heart, kidney and liver disorders etc
4. Has it been used in the past?
Ans- The therapy has been used experimentally in the past and so has become a ray of hope in the fight against the nCoV pandemic. Early 1890, it was used for treatment of Diphtheria for which nobel prize was given in 1901 to scientist Behring. It was followed by its usage in 1918 for treatment of H1N1 influenza virus (Spanish flu) pandemic in 1918.
It was off late tried by WHO for Ebola virus disease in 2014, for Middle East respiratory syndrome (MERS) in 2015, the H1N1 infection of 2009, Severe Acute Respiratory Syndrome (SARS) outbreak in 2003. Others serious outbreaks that have seen the use of this therapy are Measles, HIV, polio and mumps.
5. Any impact of Plasma Therapy on COVID-19?
Ans- The efficacy depends on the titers of antibody that the plasma therapy is able to generate in the recipient’s body. This treatment has been conducted in China and USA, where 1:1000 and 1:640 titer was observed. Depending on the antibody amount and composition, the protection conferred by the transferred antibodies can in some cases last from weeks to months. In severe and critically ill nCoV infected patients it is shown to reduce viral load, lessens the severity, improves clinical status and shortens length of illness, followed by reduction of time to recovery and duration of hospital stay
This therapy is not simple to harness, primarily due to the difficulty of obtaining significant amounts of plasma from survivors. In diseases like COVID-19, where most of the patients with severe symptoms are aged, and often suffer from other medical conditions such as hypertension, diabetes, and so on, the effectiveness remains questionable.
6. What are the possible side effects of Plasma Therapy?
Ans- The study by John Hopkins immunologists stated some of the risks associated with it:
a. Transfer of blood substances: As the blood transfusion takes place, there are risks that an inadvertent infection might get transferred to the patient.
b. Enhancement of infection: The therapy might fail for some patients and can result in an enhanced form of the infection. Sometimes the tires in recipient are seen to very low to the tune of 1:80 to 1:100 rendering them ineffective.
c. Effect on immune system: The antibody administration may end up suppressing the body’s natural immune response, leaving a Covid-19 patient vulnerable to subsequent re-infection.
d. Passage of other proteins: Sometimes albumin and other clotting factors like fibrinogen can pass on the recipient giving rise to increased chances of Clotting in vessels
7. Are there any unanswered questions?
Ans- There some issues raised by researchers like
a. What is the optimal dose of antibodies?
b. At what point during a patient’s illness should treatment be given?
c. Which patients will benefit?
d. The researchers also noted that “some participants had also received other experimental drugs, such as antivirals along with plasma therapy. This makes it difficult to precisely make out the efficacy of convalescent plasma”. These are some that need to be addressed before reaching concrete conclusions.
So while plasma therapy remains a ray of hope, we will only know the treatment’s efficacy once more studies and trials are conducted.
Dr Sunil Kumar Kota
MD (Med), DNB (Endo)
DIABETES & ENDOCARE Clinic, Berhampur