Updated: Dec 22, 2020
A patient overview of what you need to know about the safety and efficacy of convalescent plasma therapy for COVID-19.
What is Convalescent Plasma?
One method doctors use to treat infections in seriously ill patients is convalescent plasma. Plasma is the liquid portion of blood that is ~92% water and also contains antibodies.
Antibodies are proteins made by the body’s immune system that bind to foreign invaders like bacteria and viruses, facilitating their destruction.
Persons who have not been exposed to a particular bacteria or virus will not have antibodies to the infection, which are crucial for defending against disease. Using a process called apheresis, plasma can be collected from patients who recovered from COVID-19, and is presumed to be rich in antibodies to the disease. When given to patients with an active infection, it may boost their ability to fight COVID-19, potentially lessening its severity and shortening its duration.
It’s important to note that convalescent plasma is far from a new therapeutic tool, having been used historically to combat other influenzas (including the 1918 flu), as well as polio, rabies, measles and hepatitis. More recently, this method was used with some success to treat SARS-CoV-1, which is a close relative of SARS-CoV-2 (the virus that causes COVID-19), and the H1N1 flu that caused a global pandemic in 2009.
How Do We Know if Convalescent Plasma is Effective in Treating COVID-19?
While there is some limited scientific data to suggest convalescent plasma could lessen the severity and shorten the duration of COVID-19, it is critical to understand several key points about the studies conducted to date:
Although several non-controlled case studies have been conducted evaluating the efficacy of convalescent plasma in the treatment of COVID-19, only one small, randomized control trial (RCT) has been conducted to date
RCTs are the gold-standard for assessing cause-effect relationships because they provide both a control to compare the experimental treatment against (i.e., convalescent plasma vs. no plasma) and randomization of treatment, further reducing bias. Randomization employs computer programs to assign patients to the control or experimental group, enabling researchers to attribute differences in outcomes to the intervention used in the study.
Because the study conducted by Li et al. in Wuhan, China from February to April 2020 was an RCT, the results represent the best scientific evidence to date for determining the efficacy of convalescent plasma in treating COVID-19.
All results from the sole RCT conducted to date must be taken with a grain of salt. This RCT did not enroll enough individuals to generate high quality data, as it included only 103 out of the 200 desired patients.
Further RCTs with larger patient numbers are needed to determine if convalescent plasma statistically improves COVID-19 clinical outcomes.
Does Convalescent Plasma Reduce COVID-19 Disease Severity and Duration?
Short answer: we don’t know yet. Based on the sole RCT conducted to date, we can’t say definitively whether or not convalescent plasma therapy is an effective treatment for COVID-19. Preliminary data suggests convalescent plasma may be effective in reducing the symptoms of COVID-19 in severely ill patients, although not for patients with life-threatening disease (i.e., requiring mechanical ventilation to breathe). This indicates convalescent plasma generally may be effective earlier into COVID-19 disease progression.
Is Convalescent Plasma Approved for COVID-19 Therapy?
In the United States, convalescent plasma has mainly been provided under an expanded access program (EAP) lead by the Mayo Clinic. Although convalescent plasma is not an Food and Drug Administration (FDA)-approved product, the FDA can provide patients with access to investigational treatments outside of clinical trials. In the case of the current pandemic, because COVID-19 is a potentially life-threatening condition without established treatments, the FDA approved convalescent plasma under this compassionate-use program, selecting the Mayo Clinic to spearhead the initiative.
As of October 5, 2020, the Mayo Clinic program had provided convalescent plasma to over 85,000 American patients.
On August 23, 2020, the FDA issued an emergency use authorization (EUA) for convalescent plasma. This makes it easier for local hospitals to administer the treatment.
If I Get Sick with COVID-19, Will I Be Treated with Convalescent Plasma?
If you are hospitalized with COVID-19 in the United States with severe or life-threatening illness, your physician may administer convalescent plasma to you using the EUA issued by the FDA on August 23, 2020.
Prior to this issue of this EUA, physicians were able to request convalescent plasma for COVID-19 through the government-sponsored EAP led by the Mayo Clinic, which served patients in need across the entire country. Because the EUA “supersedes” the EAP, the Mayo Clinic is no longer enrolling patients for this program, as physicians can now request convalescent plasma directly from local suppliers.
Although not an RCT study, the FDA did evaluate the safety and efficacy data for patients transfused in the Mayo Clinic-led EAP program – along with other existing data – when issuing the EUA. While the EUA still doesn’t provide full FDA approval of convalescent plasma therapy for COVID-19, it does enable patients with serious or immediately life-threatening COVID-19 disease (who are not eligible or who are unable to participate in randomized clinical trials) to receive it.
Is Convalescent Plasma Therapy the Same as a Vaccine?
No. Convalescent plasma is a passive therapy, which means antibodies from one person are transferred to another, providing their immune system with a temporary boost. Alternatively, vaccines actively stimulate an individual’s own immune system to create antibodies for themselves, training it to detect and respond to specific pathogens for longer-term defense against illness.
Convalescent plasma therapy is a temporary treatment and will NOT provide long-term immunity to COVID-19.
Because convalescent plasma relies on antibodies generated by the donor, the recipient of the treatment will lose protection from COVID-19 over time as the donated antibodies are cleared from the recipient's body. Vaccines are required to impart long-lasting immunity because they enable patients to generate their own antibodies to a specific pathogen.
The Million Dollar Question – Is Convalescent Plasma an Effective Therapy for COVID-19?
We don’t know yet. Because initial data suggests earlier treatment with convalescent plasma works best, always seek medical attention if you notice the newfound appearance of any of the following symptoms:
Fever or chills
Shortness of breath or difficulty breathing
Muscle or body aches
New loss of taste or smell
Congestion or runny nose
Nausea or vomiting
Note that this list does not include all possible symptoms. The CDC will continue updating this list as new information emerges.
In summary, if you require hospitalization for COVID-19 illness and meet certain criteria, you may receive convalescent plasma therapy. Although limited scientific data suggests this treatment may lessen the severity of the disease or shorten its duration, you might not experience any benefit. Convalescent plasma therapy is a temporary treatment – not a vaccine – and will not provide long-term immunity to COVID-19.
Mucha, S.R. and N. Quraishy. (Aug 2020) Convalescent plasma for COVID-19. Cleveland Clinic Journal of Medicine, DOI: 10.3949/ccjm.87a.ccc056
Cheng, Y., et al. (2005) Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 24, 44–46
Luke, T.C. et al. (2006) Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med. 145(8):599-609
Hung, I.F., et al. (2011) Convalescent Plasma Treatment Reduced Mortality in Patients With Severe Pandemic Influenza A (H1N1) 2009 Virus Infection. Clin Infect Dis 52(4):447-456
Duan, K. et al. (2020) Effectiveness of convalescent plasma therapy in severe COVID-19 patients. PNAS 117(17):9490-9496
Shen, C., et al. (2020) Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA 323(16):1582-1589
Zhang B, et al. (2020) Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Chest 158(1):e9-e13.
Li, L., et al. (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 324(5):460-470
Harriton, E. and J.L. Locascio. (2018) Fetal microchimerism by mode of delivery: a prospective cohort study. BJOG 125(13):1716
Jeyanathan, M., et al. (2020) Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol 20, 615–632