How Does Convalescent Plasma Therapy for COVID-19 Work, Know its Benefits & Risks

As the world awaits a vaccine for the novel coronavirus pandemic, most medical experts have, in the meantime, turned to an older and tested method for fighting against infectious diseases. This treatment is known as plasma therapy or convalescent plasma therapy. This type of treatment involves using convalescent plasma, which is a component of blood, from people who have survived life-threatening infections for treating others with the same infection. The basic idea behind plasma therapy is that the antibodies against a particular virus or bacteria remain in the blood of a person who has recently recovered from an infectious disease. Doctors use these antibodies to treat others suffering from the same infection. Here’s everything you need to know about plasma therapy for COVID treatment.

What is Plasma Therapy?

Plasma therapy or convalescent plasma is a medical procedure that makes use of a component of the blood of a recovered patient for creating and passing on antibodies to other infected individuals. Plasma therapy has been used by doctors for over 100 years by taking convalescent plasma from the blood of people who survived certain life-threatening infections for treating others who have the same infection. The underlying idea behind plasma therapy is that antibodies against a virus or bacteria remain in the bloodstream of a person who has recently recovered from an infection.1

Convalescent plasma therapy was used by doctors as a major form of treatment during the 1918 Spanish flu pandemic.2 Doctors also experienced some success with this form of treatment during the 2009 swine flu (H1N1) outbreak as well as the 2014 Ebola outbreak in Africa.3,4 Additionally, in 2015, scientists confirmed using plasma therapy as the protocol for treating Middle East Respiratory Syndrome (MERS).5

During the early phases of the COVID-19 outbreak, in January 2020, doctors in China started treating severely sick patients with plasma therapy.

They also reported experiencing success and encouraging results from at least five such cases.6

In the United States, in March 2020, the Houston Methodist Hospital in Texas became the first academic medical center to start treating critically ill COVID-19 patients with plasma therapy.7 In the same month, the New York Blood Center started collecting blood plasma from people who already recovered from COVID-19.8

As doctors and scientists around the world started searching for new drugs and treatments against the novel coronavirus, convalescent plasma therapy came to the forefront as a potentially promising treatment. Soon the US Food and Drug Administration (FDA) also announced that it has put in place a process for medical centers to start conducting trials on an experimental treatment that uses blood plasma from those who have already recovered from COVID-19.9

Towards the end of May 2020, scientists reported that out of 25 patients of COVID-19, 19 treated with plasma transfusions in Texas experienced significant improvements in their condition.10 At the same time, Michigan State University and Mayo Clinic in the US have been leading programs focusing on treating COVID-19 patients with convalescent plasma therapies. Looking at the success rate of plasma therapy, in August 2020, the FDA approved the use of convalescent plasma therapy for the emergency treatment of COVID-19 patients. However, many medical experts remain of the opinion that more research is required on using such type of treatment.11

Reports of a phase 2 clinical trial that was published recently in October 2020 in The BMJ discovered that plasma therapy does not reduce the risk of patients dying from COVID-19 or from developing severe COVID-19.12

How Does Convalescent Plasma Therapy for COVID-19 Work?

Convalescent plasma therapy works by using antibodies, which are a type of proteins produced by the plasma in the blood, from patients who have already completely recovered from a COVID-19 infection. Here is the procedure of how plasma therapy helps fight against the coronavirus in the body:

Blood is drawn from a previous COVID-19 infected but now completely recovered patient. The plasma component of the blood is separated. This part of blood contains the antibodies that the immune system built up against the SARS-CoV-2 virus. This plasma is then injected into a currently infected patient’s body to help fight the virus and prevent the virus from spreading.

Once the patient has recovered, he/she will also be asked to donate their blood so that the antibodies from their blood can then be used for treating other COVID-19 patients.

All blood samples that are collected are first checked for any other underlying infectious diseases such as HIV/AIDS and hepatitis.

The blood that is taken will then be studied, and a doctor will extract the plasma component from the blood to inject into another infected patient.

What Evidence Is There To Show That Plasma Therapy Might Benefit From COVID-19?

The use of the plasma component, or convalescent plasma as it is medically known, collected from previously infected COVID-19 patients for a passive transfer of antibodies to prove protection or treating another patient. A majority of patients who have already recovered from the COVID-19 infection are known to develop circulating antibodies to several SARS-CoV-2 proteins within two to three weeks after they were initially infected. These antibodies can be detected by diagnostic tests like ELISA and other quantitative assays. The fact that these antibodies lend protection has been demonstrated in various animal studies showing that animals injected with convalescent plasma could not be re-infected with the SARS-CoV-2 virus for several weeks to months later as well.13

Numerous studies have already shown success with the use of COVID-19 convalescent plasma for treating critically or severely ill COVID-19 patients without any severe or unexpected side effects. Recently, preliminary efficacy reports from nearly 35,000 patients participating in a US FDA-sponsored expanded access program being carried out by the Mayo Clinic showed that many of the patients improved clinically. However, the exact role of COVID-19 convalescent plasma that was used in the treatment remained unclear as all the patients also received at least one additional treatment, which included antibiotics, antivirals, antifungals, and/or corticosteroids. The study found that mortality was lower in those patients who received the plasma therapy within three days of being diagnosed with COVID-19 and in those who received units of COVID-19 convalescent plasma that had higher specific IgG levels. However, the study did not perform uniform testing to look for neutralizing antibodies in all the patients.14

At this point, there is very limited randomized controlled trial data available on the efficacy of plasma therapy for treating COVID-19 patients. In a China-based randomized controlled trial, patients with severe COVID-19 infection but who were not yet intubated were found to have a faster and more frequent improvement in their symptoms with plasma infusion, as compared to the controls. However, this trial was terminated early due to the lack of patients at the site of the study as the pandemic waned in China.15

So far, the studies have provided encouraging, but inconclusive evidence to show the efficacy of convalescent plasma therapy for COVID-19. All the evidence, though, does suggest that COVID-19 convalescent plasma, ideally with a high antibody level, should be administered at an early stage, especially before the step of intubation and any development of life-threatening inflammatory end-organ failure stage. This can expedite the process of cleaning up the virus from the body and also prevent any further tissue or organ damage.

There are still numerous clinical trials that are ongoing and are investigating the use of convalescent plasma in COVID-19 patients, but those who have a less severe illness following initial infection. Trials are also ongoing to check the efficiency of plasma therapy in people who have high-risk exposure, such as those who live in households where other family members have already been diagnosed with COVID-19. Since there are many patients who also improve on their own, there is a need for a large number of subjects to show precisely how effective convalescent plasma therapy is in the case of COVID-19.

Are There Any Risks Of Plasma Therapy for COVID-19?

Even though plasma therapy has proved to be an effective treatment for COVID-19 patients, it is not without risks. It has to be performed under proper medical supervision, as there are several underlying risks associated with the procedure. Here are some of the common dangers you should be aware of before opting for plasma therapy:

  • As the process of plasma therapy involves blood transfusion, there is a risk of transmitting a potential virus from the recovered person. Even though the blood sample is run through a variety of tests, the risk is nevertheless there. A doctor also has to assess the recovered patient’s overall health before opting to collect their blood plasma for the transfusion.
  • Every person’s body reacts in a different manner to various medications and therapies. The same holds true for plasma therapy as well. Plasma therapy cannot be used in patients who have a high chance of infection or they have an underlying medical condition such as kidney disease or heart disease.
  • Getting plasma therapy does not guarantee that you will not contract the infection once again.

In the US alone, over 72,000 patients have already received plasma therapy for COVID-19. The number is significantly higher when you consider global numbers. The initial safety data was recently published for the first 5,000 COVID-19 patients in the US who received plasma therapy.16 The results showed that convalescent plasma is a relatively safe procedure. The actual incidence of severe side effects was less than one percent, and most of these were also determined to be unrelated to the plasma transfer.

Some of the other known risks of plasma transfusion include transfusion-associated circulatory overload (TACO), allergic reactions, and transfusion-associated acute lung injury (TRALI). Transfusion-associated circulatory overload includes the occurrence of any of the following four conditions within six hours of a blood transfusion – tachycardia, acute respiratory distress, increase in blood pressure, and an acute or worsening pulmonary edema.

Many medical experts and scientists around the world have also raised specific concerns regarding the administration of convalescent plasma for COVID-19. These include a potential worsening of immune-mediated tissue damage through the process of antibody-dependent enhancement (ADE), transfusion transmission of SARS-CoV-2, and blunting of endogenous immunity. However, none of these specific problems have so far occurred with plasma therapy for COVID-19.

How to Prepare for Plasma Therapy for COVID-19?

Your doctor is only going to recommend plasma therapy for you if it matches your blood type, and you do not have any other underlying medical conditions. Here’s how you can prepare for getting a plasma treatment for treating COVID-19.

Before the treatment, your doctor will assess your overall health before you undergo the actual transfusion. During this time, your healthcare team member will insert an intravenous (IV) tube into the vein of your arm.

The recovered plasma that has been taken from a recovered COVID-19 patient will then be attached to this IV tube and administered to you in slow drips. It takes around two hours for the entire procedure to finish.

After the treatment, you will be closely monitored by your doctor, and you will need to make regular visits to the hospital to continue getting assessed by the doctor. Depending on how your body reacts to the plasma transfusion and your overall health, your doctor will determine whether you require to be kept hospitalized for longer or not.

Convalescent plasma therapy is being used worldwide to treat COVID-19 patients who are severely or critically ill. Plasma therapy has emerged as one of the few defense strategies to fight against the novel coronavirus. However, there is still a need for more research to understand exactly how it helps COVID-19 patients and how efficient the procedure is. Since most studies have been done in various ways, it is difficult to judge just how effective this treatment might be based on the results of the studies and clinical trials done so far. While the treatment appears to be relatively safe, doctors and scientists worldwide continue to use it while awaiting results from more rigorous and controlled studies. As more doctors around the world use plasma therapy for treating COVID patients, more evidence will become available in the future about this procedure, and its efficacy in treating infectious diseases.

References:

  1. Redler, L.H., Thompson, S.A., Hsu, S.H., Ahmad, C.S. and Levine, W.N., 2011. Platelet-rich plasma therapy: a systematic literature review and evidence for clinical use. The Physician and sportsmedicine, 39(1), pp.42-51.
  2. Hampton, T., 2006. Blood transfusions for flu pandemic?. JAMA, 296(15), pp.1827-1827.
  3. Hung, I.F., To, K.K., Lee, C.K., Lee, K.L., Chan, K., Yan, W.W., Liu, R., Watt, C.L., Chan, W.M., Lai, K.Y. and Koo, C.K., 2011. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clinical Infectious Diseases, 52(4), pp.447-456.
  4. Winkler, A.M. and Koepsell, S.A., 2015. The use of convalescent plasma to treat emerging infectious diseases: focus on Ebola virus disease. Current Opinion in Hematology, 22(6), pp.521-526.
  5. Arabi, Y., Balkhy, H., Hajeer, A.H., Bouchama, A., Hayden, F.G., Al-Omari, A., Al-Hameed, F.M., Taha, Y., Shindo, N., Whitehead, J. and Merson, L., 2015. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus, 4(1), pp.1-8.
  6. Shen, C., Wang, Z., Zhao, F., Yang, Y., Li, J., Yuan, J., Wang, F., Li, D., Yang, M., Xing, L. and Wei, J., 2020. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. Jama, 323(16), pp.1582-1589.
  7. Salazar, E., Perez, K.K., Ashraf, M., Chen, J., Castillo, B., Christensen, P.A., Eubank, T., Bernard, D.W., Eagar, T.N., Long, S.W. and Subedi, S., 2020. Treatment of COVID-19 Patients with Convalescent Plasma in Houston, Texas. medRxiv.
  8. Time. 2020. New York Center First To Collect Plasma From COVID-19 Patients As Possible Treatment. [online] Available at: <https://time.com/5809955/blood-plasma-coronavirus/> [Accessed 7 November 2020].
  9. U.S. Food and Drug Administration. 2020. Investigational COVID-19 Convalescent Plasma – Emergency Inds. [online] Available at: <https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma> [Accessed 7 November 2020].
  10. Salazar, E., Christensen, P.A., Graviss, E.A., Nguyen, D.T., Castillo, B., Chen, J., Lopez, B.V., Eagar, T.N., Yi, X., Zhao, P. and Rogers, J., 2020. Treatment of coronavirus disease 2019 patients with convalescent plasma reveals a signal of significantly decreased mortality. The American journal of pathology, 190(11), pp.2290-2303.
  11. Fda.gov. 2020. [online] Available at: <https://www.fda.gov/media/141479/download> [Accessed 7 November 2020].
  12. Tanne, J.H., 2020. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients. Bmj, 368, p.m1256.
  13. Rogers, T.F., Zhao, F., Huang, D., Beutler, N., Burns, A., He, W.T., Limbo, O., Smith, C., Song, G., Woehl, J. and Yang, L., 2020. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science, 369(6506), pp.956-963.
  14. Medrxiv.org. 2020. [online] Available at: <https://www.medrxiv.org/content/10.1101/2020.08.12.20169359v1.full.pdf> [Accessed 7 November 2020].
  15. Li, L., Zhang, W., Hu, Y., Tong, X., Zheng, S., Yang, J., Kong, Y., Ren, L., Wei, Q., Mei, H. and Hu, C., 2020. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. Jama.
  16. Jci.org. 2020. JCI -Early Safety Indicators Of COVID-19 Convalescent Plasma In 5000 Patients. [online] Available at: <https://www.jci.org/articles/view/140200/pdf> [Accessed 7 November 2020].

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