Convalescent Plasma Therapy: A Promising Way Out?

On 11th March 2020, World Health Organization (WHO) declared coronavirus infectious disease 2019 (COVID-19), a global pandemic. Since then life has changed for us. Coronavirus gets its name from the Latin word corona which means “crown”, because of spikes on the virus. This gives it the appearance of wearing a crown. Members of  Coronaviridae circulate in human populations but often cause mild symptoms. Others such as Middle East respiratory coronavirus (MERS-CoV) and severe acute respiratory symptom coronavirus (SARS-CoV) were transmitted from animals to humans. Severe acute respiratory coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 outbreak, which was reported first in Wuhan, Hubei province, China in December 2019. It closely resembles SARS-CoV. Worldwide, researchers are working round the clock to find a possible cure.

How does this virus enter our lungs? COVID-19 or SARS-CoV2 is an enveloped virus. The spike (S) protein of COVID-19 virus helps in entry. The S protein has two domains S1 and S2. Entry is dependent on the S1 domain of S protein that interacts with angiotensin converting enzyme 2 (ACE2) which is expressed on the surface of our lung cells. It is more of a lock and key interaction, where the S1 is like a key and ACE2 is a lock. Now the next task will be to push the door open. For that, the virus must fuse with lung cells. This is done via a series of events. Currently, there are no treatments available for COVID-19. Treatment is mainly dependent on trial and error use of antiretrovirals like fapipiravir, remedisivir, chloroquine etc., and supportive treatment like mechanical ventilation for critical cases.

Convalescent plasma therapy- a ray of hope? So how do we define convalescent plasma? Whenever we are infected with any bacteria or virus, our body begins a fight against it, and one of the arms used for this is antibody. Antibodies are Y shaped small molecules which can bind components of the infectious agents like some protein molecules present on the surface and helps in clearing them from our system. Patients who recovered from COVID-19 are expected to have neutralizing antibodies to it. The sera from such patients can be isolated and used as a passive antibody therapy. This approach is defined as the convalescent plasma therapy. The serum sample is collected using routine blood withdrawal and then followed by centrifugation. By this process, approximately 180 to 220 ml of convalescent plasma may be collected from one recovered patient and stored at -60°C temperature for up to a year. Another way of collection is by using a cell separator machine or aphresis machine that separates the components of blood. Up to 600 ml of sera can be obtained through this and stored for a year. The sera can then be used for therapeutic plasma exchange that will help in removal of unwanted harmful components like inflammatory mediators from COVID-19 patients. The plasma of a COVID-19 patient contains huge amounts of inflammatory mediators called cytokines which can cause a cytokine storm, damaging lungs and other organs. Thus, this therapeutic plasma exchange can be used for critically ill patients who are suffering from sepsis with or without a life support system. Additionally, as the sera would contain neutralizing antibodies, it would help in preventing further attack by the replicating virus. China and New York have already started the use of convalescent plasma for treating severely ill patients. In India, Kerala is the first state to start collecting convalescent plasma for therapy. Interestingly though, due to aggressive screening and early intervention, they do not have enough critically ill patients to perform clinical trials. This is an age-old time-tested therapy. Although COVID-19 is highly infectious in nature, the mortality rate is about 5.5% in China, 5.3% in US, 3.1 % in Germany and 3.4% in India as of 19th April, 2020. Compared to this, the death rate of SARS and MERS were 9.6% and 34% respectively. Thus, with aggressive screening, quick intervention and maintaining distancing measures of at least 2 meters, it is possible to flatten the growth curve of COVID-19. Additionally, convalescent plasma therapy would be useful in treating critically ill patients.


References:

1. Worldometer: https://www.worldometers.info/coronavirus/#countries

2. Hoffmann et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell (2020), https://doi.org/10.1016/j.cell.2020.02.052

3. Discovering drugs to treat coronavirus disease 2019 (COVID-19):  https://doi.org/10.5582/ddt.2020.01012

4. Effectiveness of convalescent plasma therapy in severe COVID-19 patients: Proceedings of the National Academy of Sciences Apr 2020, 202004168; DOI: 10.1073/pnas.2004168117

5. Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during Outbreaks: https://www.who.int/csr/resources/publications/ebola/convalescent-treatment/en/

6. Keith, P., Day, M., Perkins, L., Moyer, L., Hewitt, K., & Wells, A. (2020). A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19.

7. Potent human neutralizing antibodies elicited by SARS-CoV-2 infection

8. https://www.biorxiv.org/content/10.1101/2020.03.21.990770v2

9. How blood from coronavirus survivors might save lives: https://www.nature.com/articles/d41586-020-00895-8

10. https://economictimes.indiatimes.com/news/politics-and-nation/kerala-institute-ready-for-plasma-trials-but-has-no-patients-to-test/articleshow/75210857.cms

11. John Hopkins Resource centre for coronavirus: https://coronavirus.jhu.edu/data/mortality

12. Worldometer: https://www.worldometers.info/coronavirus/coronavirus-death-rate/


This article was written by Tanaya Roychowdhury. She is a Graduate Student at the Indian Institute of Chemical Biology, Kolkata, India.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: