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COVID-19 and Convalescent Plasma: Frequently Asked Questions

(Version 4.0; last updated May 8, 2020)

Input from Drs. Beth Shaz, Cindy Dunbar, and Chris Hillyer

Note: Please review ASH's disclaimer regarding the use of the following information.

What is the evidence that convalescent plasma might be beneficial in COVID-19?

The use of convalescent plasma collected from previously infected individuals to passively-transfer antibodies in order to protect or treat humans dates back almost 100 years, with some evidence for benefit against rabies, hepatitis B, polio, measles, influenza, Ebola and other  pathogens.1,2 Results from small case series during the prior MERS and SARS coronavirus outbreaks documented safety and faster viral clearance following convalescent plasma administration, particularly when given early in the disease course.

Rhesus macaques infected with SARS-CoV-2 generated antibody responses and could not be re-infected with the virus. Two publications from China reported use of convalescent plasma to treat fifteen critically ill patients without adverse events.3,4 All eventually improved clinically and cleared virus, however the impact of the convalescent plasma treatment in these patients is unclear because all patients received at least one additional therapy including antivirals, antibiotics or antifungals, and corticosteroids.

What are the theoretical benefits of convalescent plasma for COVID-19?

Convalescent plasma could provide short-medium term humoral immunity against the SARS-CoV-2 coronavirus. The vast majority of patients who recover from COVID-19 illness develop circulating neutralizing antibodies to various SARS-CoV-2 proteins 2-3 weeks following infection, detectable by ELISA or other quantitative assays. Transfer of plasma from these patients should neutralize virus, preventing further replication and halting ongoing tissue damage. This approach would be predicted to work best in patients with less severe infection, earlier in the disease course, or prophylactically in highly susceptible individuals such as exposed health care workers or family caregivers of COVID-19 patients.

What are the potential risks of convalescent plasma for COVID-19?

Convalescent plasma transfusion appears safe as over 7000 units have been transfused to date in the US. Known risks of plasma transfusion include inadvertent infection with another infectious pathogen, as with any blood product, general reactions such as transfusion-associated circulatory overload (TACO), and transfusion-associated acute lung injury (TRALI) in patients with already severe lung damage.2 Additional concerns include potential worsening of immune-mediated tissue damage via the poorly understood phenomenon of antibody-dependent enhancement, and blunting of endogenous immunity to the virus. Thus far, these risks remain theoretical. Importantly, blood product transmission of the SARS-CoV-2 virus has not been documented and is extremely unlikely for a respiratory virus.

What mechanisms exist for providers to access COVID-19 convalescent plasma therapy clinical trials or other mechanisms to deliver this treatment to patients?

In the US, on March 24, 2020, the FDA announced an emergency IND (eIND) process to allow individual physicians to treat patients with serious COVID-19 disease with convalescent plasma. On April 7, 2020, the FDA announced a National Expanded Access Protocol administered through the Mayo Clinic. The protocol enables a wider range of adults to be treated with convalescent plasma by including those at risk of severe disease as well as those with severe disease. Lastly, there are a number of FDA-approved multicenter clinical trials ongoing, focused on a variety of study subjects, including high-risk individuals for prophylaxis, or patients with mild disease, serious but not critical disease, ICU patients, or children. Similar efforts are ongoing around the world.

The use of convalescent plasma is an interim approach during development of hyperimmune globulin, vaccines and drug therapies. While the concept of plasma treatment is simple, numerous steps are involved, requiring cooperation between multiple entities including recovered patients who serve as donors, blood centers or other plasma collection centers, treating physicians and their patients, and health care administrators and regulators overseeing the safety of each step2. Use of plasmapheresis to collect large volumes of plasma would be desirable. Current estimates suggest a single donor collection could be used to treat 2-3 recipients. In addition, quantitative serologic assays are not yet widely available to identify donors with high titer neutralizing antibodies. However, as more assays become available, results are being correlated with neutralizing antibody titers. Additional questions remain including dosing, optimal antibody types (IgM, IgG, and/or IgA), and timing of administration during disease course.

How do recovered individuals sign-up to donate convalescent plasma?

Potential donors must have had documented SARS-CoV-2 infection, be symptom-free for at least 14 days, and meet standard blood donor eligibility requirements. Since new blood center sites for plasma collection are being set up almost daily, information is rapidly evolving. Listed below are some sites for referral of potential donors:

  • AABB: Information about convalescent plasma donation and a feature that helps potential donors locate AABB-accredited donation sites. Donors then contact these centers for more information on eligibility.
  • FDA -- Donate COVID-19 Plasma: Lists places to donate convalescent plasma for transfusion or for manufacturing of hyperimmune globulin .

What other passive immunity therapies are being developed for COVID-19?

Pharmaceutical companies are beginning to develop purification procedures to produce potent concentrated neutralizing antibodies from convalescent sera and immunizing large animals such as horses and cows with SARS-CoV-2 proteins in order to create antiserum. Biotechnology companies are racing to develop cocktails of monoclonal antibodies active against the SARS-CoV-2 virus, but clinical trials are months away.

References

  1. Casadevall A, Pirofski L. The convalescent sera option for containing COVID-19. J Clin Invest, 10.1172/JCI138003.
  2. Bloch EM, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19, J Clin Invest, 10.1172/JCI138745.
  3. Shen C, Wang Z, Zhao F et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA, doi:10.1001/jama.2020.4783.
  4. Duan K, Liu B, Cesheng L, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. PNAS 2020 117 (17) 9490-9496
     

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