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Table of Contents
Convalescent Plasma FDA Approved, but NOT for COVID-19 Share
Convalescent Plasma
Summary

Drug Summary

Class and Mechanism

Treatment Guidelines

Dosing

DRUG SUMMARY Contraindications

FDA Status
Convalescent plasma is a biologic agent that has been used in the treatment of infectious diseases for nearly 100 years. Recently, it has been used in the
treatment of H1N1 influenza virus,[1] severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1),[2] and Middle East respiratory syndrome Adverse Effects

coronavirus (MERS-CoV).[3] The rationale to use convalescent COVID-19 antibody-positive plasma to treat persons with active COVID-19 Useis In
based on the
Pregnancy
prior experience treating other similar respiratory viruses.[2,4,5,6] Available limited data from three small case series (combined total of 19 patients)
Citations
reported from China have provided initial encouraging results.[7,8,9] In the United States, there are now three major options for obtaining convalescent
plasma for persons with severe COVID-19 infection. These options include: Figures

1. U.S. Clinical Trials for Convalescent Plasma to Treat COVID-19: Multiple clinical trials are now ongoing in the United States that are evaluating the
efficacy of convalescent plasma for hospitalized persons with COVID-19 infection.

2. National Convalescent Plasma Expanded Access COVID-19 Treatment Protocol : In this national expanded access program, the U.S. Food and Drug
Administration (FDA) will coordinate efforts to obtain and provide convalescent plasma (from persons who have recovered from COVID-19) as
therapy for hospitalized patients with COVID-19. The Mayo Clinic will serve as the lead institution for the program and the American Red Cross will
help collect plasma (see below) and distribute it for use in patients across the country (see below). To participate in the expanded access program,
physicians must first register their institutions and potential patients in the Mayo Clinic’s database. NOTE: as of April 14, this program had 436
patients enrolled and 118 had completed transfusions.

3. Single-Patient Convalescent Plasma for COVID-19 Emergency IND : On April 3, 2020, the FDA announced the availability of a single-patient
emergency Investigational New Drug Application (eIND) for the individual patient. This process allows the use of an investigational drug for the
treatment of an individual patient by a licensed physician upon FDA authorization. The eIND process is not for the use of COVID-19 convalescent
plasma for the prevention of infection. The FDA has provided a Frequently Asked Questions related to this eIND.

On May 1, 2020, the U.S. FDA issued Recommendations for Investigational COVID-19 Convalescent Plasma as guidance for health care providers and
investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19
(COVID-19 convalescent plasma) during the public health emergency.

For this national program to work, it is essential that donors who have recovered from COVID-19 infection have an easy mechanism to donate plasma for
the national expanded access program for convalescent plasma to treat hospitalized persons with COVID-19.

Red Cross Convalescent Plasma Donor Program : The Red Cross is now seeking people who are fully recovered from COVID-19 and may be able to
donate plasma to help current patients with serious or immediately life-threatening COVID-19 infections. In addition, the Red Cross Convalescent
Plasma Donor Program provides information for both (1) potential plasma donors who have had COVID-19 and are fully recovered and (2) clinicians
who are interested in receiving convalescent plasma to treat a patient with active COVID-19, or who want to refer potential donors. The Red Cross
Program is in partnership with the Mayo Clinic.

CLASS AND MECHANISM

Convalescent plasma is a blood product believed to provide passive antibody therapy through the transmission of neutralizing viral
antibodies. Plasma is the liquid portion of blood that contains proteins, including antibodies (Figure 1). Plasma is obtained from a
donor through apheresis, a process where whole blood is taken from the donor, the plasma is separated from the red blood cells,
and the red blood cells are returned to the donor (Figure 2). The concept of using convalescent plasma to treat COVID-19 first
requires identifying a donor who has recovered from COVID-19 and has significant titers of SARS-CoV-2 neutralizing antibodies. The
donor then undergoes apheresis to obtain the plasma, which is rich in antibodies. The plasma is then submitted to a blood bank
and subsequently given to an ABO-compatible hospitalized patient with active COVID-19 infection (Figure 3).

TREATMENT GUIDELINES

NIH Covid-19 Treatment Guidelines

The following is a summary of the NIH COVID-19 Treatment Panel (the Panel) recommendations for Convalescent Plasma (May 12,
2020).[10]

Treatment: There are insufficient clinical data to recommend either for or against the use of convalescent plasma or
hyperimmune immunoglobulin for the treatment of COVID-19 (AIII).

Preexposure Prophylaxis: The COVID-19 Treatment Guidelines Panel (the Panel) does not recommend the use of any agents
for preexposure prophylaxis (PrEP) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside of the setting
of a clinical trial (AIII).

Postexposure Prophylaxis: The Panel does not recommend the use of any agents for postexposure prophylaxis (PEP) against
SARS-CoV-2 infection outside of the setting of a clinical trial (AIII).
DOSING

There are very limited data for the use of convalescent plasma to treat persons with COVID-19 and no standard dosing
recommendations exist for persons with COVID-19. Therefore, the following summarizes currently available information on dosing
convalescent plasma to treat persons with COVID-19.

In the protocol for a study in the United States, participants with COVID-19 and acute respiratory symptoms will receive 1-2
units (300 mL per unit, total amount 300-600 mL) of convalescent plasma.

In the United States National Convalescent Plasma Expanded Access COVID-19 Protocol [NCT04338360 ] the dose is 1 unit of
plasma (at least 200 mL).

In the published study from China, each of the 5 patients with COVID-19 received 2 consecutive infusions of 200 mL of plasma
for a total of 400 mL.[7]

In a preprint article from China that has not been peer reviewed, each of 10 patients with severe COVID-19 received one 200 mL
infusion of convalescent plasma derived from recently recovered donors who had SARS-CoV-2 neutralizing antibody titers
above 1:640.[8]

Infusion Rate: The recommended infusion rate is 100-250 mL/hr. To minimize any allergic or nonhemolytic transfusion-related
reactions, it is also recommended that persons can receive premedication with acetaminophen and diphenhydramine.

CONTRAINDICATIONS

Receipt of incompatible ABO plasma.

A prior major reaction to transfusion blood products could be considered a contraindication to receiving convalescent plasma. Figure 1. Compone

FDA STATUS

On April 3, 2020, the U.S. FDA announced the availability of a single patient Emergency Investigational New Drug Application (eINDs)
for the use of convalescent plasma to treat an individual patient with COVID-19. This process allows the use of an investigational
drug for the treatment of an individual patient by a licensed physician upon FDA authorization. The eIND process is not for the use
of COVID-19 convalescent plasma for the prevention of infection. The FDA has provided a Frequently Asked Questions related to
this eIND.

On May 1, 2020, the U.S. FDA issued Recommendations for Investigational COVID-19 Convalescent Plasma as guidance for health
care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals
who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency.

ADVERSE EFFECTS

The risk profile is similar to the receipt of other blood products, including allergic reactions to the plasma and acquisition of
infections. The Red Cross employs a rigorous Infectious Diseases Screening Process for blood products. See also the U.S. FDA’s
Complete List of Donor Screening Assays for Infectious Agents and HIV Diagnostic Assays .

USE IN PREGNANCY

Pregnancy: The use of convalescent plasma has not been studied in pregnancy. In a small case series of four critically ill
patients in China who received convalescent plasma and recovered from COVID-19, one of the patients was pregnant.[9] Given
that the risk profile is thought to be similar to that of other blood products, the risks and benefits of use should be determined
on a case-by-case basis.

Breastfeeding: The use of convalescent plasma has not been studied in individuals who are breastfeeding.

Eligibility in Clinical Trials: Pregnant and breastfeeding individuals are eligible to enroll in the National Convalescent Plasma
Expanded Access Protocol, if they meet other enrollment criteria [NCT04338360 ].

CITATIONS

1. Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A
(H1N1) 2009 virus infection. Clin Infect Dis. 2011;52:447-56.
[PubMed Abstract ]

2. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune
immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory
meta-analysis. J Infect Dis. 2015;211:80-90.
[PubMed Abstract ]

3. Ko JH, Seok H, Cho SY, et al. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus
infection: a single centre experience. Antivir Ther. 2018;23:617-22.
[PubMed Abstract ]

4. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020;130:1545-8.
 [PubMed Abstract ]
Figure 2. Process o
5. Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. 2020 Mar 27. [Epbu ahead of Plasma
print]
[PubMed Abstract ]

6. Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020;20:398-400.
[PubMed Abstract ]

7. Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Mar 27.
[Epub ahead of print]
[PubMed Abstract ]

8. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A.
2020;117:9490-6.
[PubMed Abstract ]

9. Zhang B, Liu S, Tan T, et al. Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection. Chest. 2020
Mar 31.[Epub ahead of print]
[PubMed Abstract ]

10. National Institutes of Health (NIH). COVID-19 Treatment Guidelines. May 12, 2020
[NIH ]

FIGURES

Figure 3. Concept
Plasma to Treat CO

Figure 1. Compone
 Figure 2. Process o
Plasma

Figure 3. Concept
Plasma to Treat CO

Figure 1. Components of Whole Blood

Figure 2. Process of Apheresis to Obtain Plasma

Figure 3. Concept of Using Convalescent Plasma to Treat COVID-19

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