Convalescent Plasma Therapy: A possible cure for Covid-19?

On 28th April 2020, the spokesperson for the Health Ministry of India made an announcement that Plasma Therapy would not be allowed as a cure for the Covid-19 virus, other than for clinical trials. This came as a disappointment to many in the Medical fraternity as well as the general public. But it also brought a lot of attention to this rather interesting therapy which has been around for a long time but few people are aware of. 

What is plasma?

The blood is made up of various components such as red blood corpuscles, white blood corpuscles, platelets and other cellular components suspended in a fluid called plasma. The above components can be easily separated out to give a clear straw-coloured liquid which is the plasma, also called serum. 55% of the blood is made up of plasma making it the largest component of human blood. The fluid contains water, salts, enzymes, antibodies and other proteins.

What is CPT? 

Whenever a disease-causing pathogen attacks the human body, the body’s immune system produces a reaction to counter the attack. Proteins called antibodies are produced in the human blood and they play a significant role in fighting the disease. Interestingly, these antibodies can be isolated from the blood of one person and transferred to the blood of another. This concept is the basis for Convalescent Plasma Therapy or CPT. 

Convalescent refers to a person who is recovering from an illness, as in this case caused by a bacteria or virus. Such a person would have a higher level of antibodies in his/her blood than somebody who is not infected by those viruses/bacteria. So, when some amount of plasma along with these antibodies is isolated from the convalescent’s blood and transferred to the blood of a person severely affected by the virus, the latter’s chances of recovering are much better. This is CPT or CST (Convalescent Serum Therapy).

History of CPT

In 1890, Emil von Behring, a German physiologist, discovered that the serum obtained from a rabbit infected with diphtheria was effective in treating patients infected with diphtheria or even preventing an infection in healthy people. This won Behring the first-ever Nobel prize for medicine in 1901. This concept was of great help in the first half of the 20th century. It was used during the Spanish flu pandemic of 1918, a diphtheria outbreak in the 1920s, a flesh-eating bacteria epidemic in the 1930s, etc. It was used to treat various ailments caused by bacteria or viruses much before a vaccine for them was developed. 

However, back then, CPT was not as effective as it is today. The main reason for this is the difficulty in separating out desired antibodies from the serum. Along with desired antibodies, the serum contained unintended antibodies and impurities that could cause side-effects in patients. Later, advances in medical technology made it easy to separate out desired antibodies and ever since then, CPT has been a popular remedy.

CPT in recent times

In the last 20 years, CPT has been used to treat patients affected by Ebola virus and H1N1 (which causes swine flu), as well as corona viruses that caused the SARS outbreak in 2003 and MERS outbreak in 2012. During the recent SARS outbreak in Hong Kong, 70 to 80 patients were treated using CPT and they recovered faster than those who did not get CPT.

CPT and Covid-19

Ever since the Covid-19 outbreak, hospitals, universities and research Institutions in the US, China and Italy, some of the worst-affected countries, have been experimenting with CPT to treat Covid-19 patients. This includes Houston Methodist Hospital and John Hopkins University in the US, Chongqing Medical University, China, and Pisa University Hospital, Italy. They have also published white-papers on this topic.

India has been more cautious on this topic. India’s Central Drugs Standard Control Organisation (CDSCO) has permitted the Indian Council of Medical Research (ICMR) to conduct clinical trials for CPT. However; the ICMR has refused permission to use CPT as a definite cure on Covid-19 patients. One reason could be that in most cases, the patients with severe symptoms are aged, and suffer from other medical conditions such as hypertension, diabetes. So would CPT be effective or would it cause other complications is the question. 

Also, if the level of antibodies present in the plasma extracted from a convalescent is not adequate, CPT would not be effective. This implies, a lot of screening must be done to choose convalescents with high levels of desired antibodies in their blood. 

So how can CPT be used in India, currently?
There are 3 possibilities, provided the Health Ministry gives its approval. 

1. On compassionate grounds for extremely, critically-ill patients. This is what Mount Hospital has been doing in New York where-in, severely-ill or critically-ill patients who are in a life-threatening stage are given CPT on compassionate grounds, for which FDA (Federal Drug Administration) has given approval.
   
2. FDA has given limited approval for John Hopkins University to use CPT for frontline doctors, not across the USA but only for doctors testing patients at John Hopkins Hospital. The logic is that frontline workers are exposed more to Covid-19 than anybody else by working with affected patients. So, if antibodies from recovering patients are given to frontline doctors treating such patients, they could treat them more confidently.
   
3. There is a third group for which FDA approval is awaited but a proposal has been put forward. These are Covid-19 patients who are admitted to the hospital but are not very sick. As you may know, 80% of all Covid-19 patients can be treated within the community itself, 15% are going to be very sick and will be hospitalized, while 5% cases will be very sick.

Conclusion

CPT is neither new nor a novel concept. Also, the technology to extract plasma is not very complex and is done routinely in our day-to-day lives. Until further evidence is available, its use should be restricted to research settings.

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