What is convalescent plasma therapy for COVID-19?
There are few emergency use treatment options for the Coronavirus Disease 2019 (COVID-19) pandemic and no approved vaccine. On August 23, 2020 the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for use of convalescent plasma for COVID–19 treatment.
According to the FDA, "this product may be effective in treating COVID-19 and that the known and potential benefits of the product outweigh the known and potential risks of the product." The FDA believes that COVID-19 convalescent plasma may be effective in lessening the severity or shortening the length of COVID-19 illness in some hospitalized patients.
However, according to the National Institutes of Health (NIH), there are insufficient data to recommend either for or against the use of COVID-19 convalescent plasma for the treatment of COVID-19.
An EUA does not require the same strict study standards that are required for full FDA drug approvals. The EUA would allow doctors across the U.S. to treat patients with the plasma therapy, but whether this will allow greater access to the treatment is not known yet.
EUAs have been enacted for other COVID-19 treatments, including the antiviral remdesivir and the malaria treatment hydroxychloroquine. However, the EUA for hydroxychloroquine was revoked by the FDA in June 2020 due to lack of effectiveness and concerns over heart safety
In addition, as stated by the FDA, COVID-19 convalescent plasma does not yet represent a new standard of care based on the current available evidence.
- To date, prospective, randomized, placebo-controlled studies, the gold standard to determine the effectiveness of a drug treatment, are not available to assess convalescent plasma therapy in COVID-19 patients.
- Many plasma therapy studies are retrospective, open-label, case-controlled, or not adequately powered because they looked at too few patients.
- Confounding factors, such as lack of control or additional treatments received (such as remdesivir or steroid treatments) can complicate results. In fact, a recent study in the Netherlands was halted early because most COVID-19 patients already had high neutralizing antibody titers at hospital admission.
Previously, in March 2020 the FDA had already established a pathway for doctors to obtain convalescent plasma therapy for specific patients in the U.S. via a single-patient emergency Investigational New Drug Application (eIND) and compassionate use. The first patient in the U.S. received this therapy at the end of March at Houston Methodist Hospital in Texas. The American Red Cross also has established pathways for recovered COVID-19 patients to donate plasma. Currently, over 70,000 patients have received plasma therapy in the U.S.
What is convalescent plasma?
- Convalescent plasma is a liquid part of the blood that contains antibodies (proteins) to certain infections, such as to COVID-19.
- Convalescent plasma for COVID-19 is collected from eligible patients who have fully recovered from the virus.
- Patients who donate must have a documented laboratory-confirmed diagnosis of COVID-19, negative results of the disease, and complete resolution of symptoms for at least 14 days prior to donation.
- This plasma can be harvested and used for patients who require further options.
- During convalescent plasma therapy, plasma from blood donors who have recovered from COVID-19 is infused into patients to supply a source of antibody against the coronavirus (SARS-CoV-2).
Convalescent plasma therapy is a century-old technique used to supply antibodies to critically ill patients who have few, if any, treatment options left. Convalescent plasma therapy has been used in many other viral illnesses in past history, including Ebola, diphtheria, 2003 SARS-CoV, the 2009 influenza A (H1N1) outbreak, and even the Spanish flu pandemic of 1918.
How does convalescent plasma therapy work?
Convalescent plasma therapy works differently than a vaccine. When you receive a vaccine, your immune system produces its own antibodies to the microbe you are being protected against. These antibodies have a type of memory, and when you are exposed to the target virus or bacteria in the future, your body is able to activate the antigens and attack the pathogen. Some vaccines can last a lifetime with one shot. This is known as “active immunity”.
Convalescent plasma therapy offers a short-term type of “passive immunity”. You receive the antibodies via injection of plasma from a donor who has successfully fought off the COVID-19 disease. The antibodies may help fight off the virus and allow a patient time to develop their antibodies for recovery. This may be especially useful as no vaccine for COVID-19 currently exists, although vaccine studies are progressing.
Is convalescent plasma therapy effective for COVID-19?
Studies are still ongoing to determine the overall effectiveness of COVID-19 plasma therapy. No placebo-controlled, randomized clinical trials are available, to date.
The FDA states that the EUA is not intended to replace randomized clinical trials. Patient enrollment of patients into ongoing randomized clinical trials is critically important for the definitive demonstration of safety and efficacy of COVID-19 convalescent plasma.
On August 13, 2020 Mayo Clinic released a preprint study (not yet peer-reviewed) of COVID-19 plasma therapy which enrolled over 35,000 patients. However, the open-label study did not include a placebo-controlled group, so the true treatment effect cannot be determined.
- The main outcome measures was 7- and 30-day mortality. Patients were especially critical, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion.
- The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001).
- Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Higher concentration of antibodies in the transfused plasma appeared to be linked with lower mortality rates.
Are there side effects with convalescent plasma therapy?
Plasma transfusions are generally safe and well-tolerated by most patients, but serious side effects have been reported. Possible side effects include:
- mild fever
- allergic reactions
- transfusion reactions
- acute lung injury
- very rare risk of infectious disease transmission via the donated plasma (i.e., HIV, hepatitis B or hepatitis C virus)
In June 2020, Mayo Clinic released results from a large study with 20,000 patients that suggested COVID-19 plasma therapy was safe in a diverse group of patients. Serious adverse event rates were low and less than 1%, including transfusion reactions and thrombotic (blood clotting) events. Adverse cardiac events occurred in about 3% of patients, but 88% of these events were deemed unrelated to the plasma transfusion by the treating physicians.
I have recovered from COVID-19. Can I donate convalescent plasma?
If you have recovered from COVID-19, and you are eligible for blood donations otherwise, you may be able to donate. Certain conditions must be met:
- You must have had a prior diagnosis of COVID-19 documented by a laboratory test and meet other laboratory criteria. If you did not receive a test for COVID-19, and only think you might have had it, you are not eligible to donate.
- You must have fully recovered from COVID-19 without any symptoms for at least 14 days before donation.
Contact your local blood banks or ask your doctor about convalescent plasma donations for COVID-19.
- Convalescent plasma for COVID-19 is collected from eligible patients who have fully recovered (without symptoms) from the virus for at least 14 days. Donors who are eligible may donate through the American Red Cross or other local blood banks.
- In order to donate you will need to meet other specific criteria, including a documented lab test that proves you had a diagnosis of COVID-19.
- The FDA has now approved an Emergency Use Authorization (EUA) process for convalescent plasma therapy. An EUA can be issued on an investigational agent when the FDA believes a treatment is effective in treating COVID-19 and that the potential benefits of the product outweigh the potential risks. Doctors across the nation may have easier access to the treatment for their patients, but volunteer enrollment is well-controlled clinical studies of plasma therapy may decline.
- Robust studies are limited for convalescent plasma therapy for COVID-19; to date, no placebo-controlled, randomized studies are available to assess treatment effectiveness or safety.
- Shen C, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. Published online March 27, 2020. doi:10.1001/jama.2020.4783
- Chen L, et al. Convalescent plasma as a potential therapy for COVID-19. The Lancet Infectious Diseases. Published online February 27, 2020. DOI: https://doi.org/10.1016/S1473-3099(20)30141-9
- Aleccia J. Blood centers will collect plasma from COVID-19 survivors in bid for treatment. Kaiser Health News.
- FDA grants first approval of convalescent plasma therapy in COVID-19 patient. Drugs.com MedNews. Accessed March 31, 2020 at https://www.drugs.com/news/fda-grants-first-approval-convalescent-plasma-therapy-covid-19-patient-89304.html
- FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment. Drugs.com Accessed August 23, 2020 at https://www.drugs.com/news/fda-issues-emergency-authorization-convalescent-plasma-potential-promising-covid-19-92296.html
- Joyner M, et al. Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience. medRxiv 2020.08.12.20169359. doi: https://doi.org/10.1101/2020.08.12.20169359
- Gharbharan, A, et al. Convalescent Plasma for COVID-19. A randomized clinical trial. medRxiv. 2020.07.03. doi: https://doi.org/10.1101/2020.07.01.20139857
- Joyner M, et al. Safety Update: COVID-19 Convalescent Plasma in 20,000
Hospitalized Patients. Mayo Clinic Proceedings. 2020. Accessed August 24, 2020 at https://mayoclinicproceedings.org/pb/assets/raw/Health%20Advance/journals/jmcp/jmcp_ft95_6_8.pdf
- National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Convalescent Plasma. Updated 2020 Jul 17. Accessed August 24, 2020 at https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/blood-derived-products/convalescent-plasma/
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