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COVID-19 convalescent plasma

Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Kyle Annen, D.O.

Topic Completed: 24 November 2020

Minor changes: 23 February 2021

Copyright: 2020-2021, PathologyOutlines.com, Inc.

PubMed Search: COVID-19[TI] convalescent plasma[TI] transfusion

See Also: COVID-19 lung pathology, COVID-19 testing, COVID-19 viral hepatitis

Kyle Annen, D.O.
Page views in 2020: 137
Page views in 2021 to date: 115
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Transmission | Symptoms | Blood donor screening | Blood donor testing | Donor deferral | Laboratory | Case reports | Treatment | Sample assessment & plan | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Annen K. COVID-19 convalescent plasma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedcovid19convplasma.html. Accessed April 19th, 2021.
Definition / general
  • Convalescent plasma is obtained from a blood donor who has recently recovered from the relevant infection
    • Considered experimental or investigational and must be approved by the FDA for each disease entity
    • Approved as an investigational new drug (IND) by the FDA on March 27, 2020; patients who have recovered from COVID-19 are eligible to donate convalescent plasma after they have been symptom free for 14 days, with 1) proof of infection (positive PCR by nasopharyngeal swab or positive antibody titer) and 2) eligible for regular blood transfusion
  • Effectiveness of COVID-19 convalescent plasma (CCP) in patients has not been definitively proven; benefit suggested by studies where CCP is transfused < 3 days after admission and with a high titer of neutralizing antibodies
  • For disease specific information, see Lung - COVID-19 topic
Essential features
  • COVID-19 convalescent plasma is an investigational blood product used to treat patients who are infected with the novel coronavirus
  • Donors must test positive for COVID-19 by PCR nasopharyngeal swab or antibody testing, be symptom free for 14 days and pass all standard blood donation criteria
  • Recipients are eligible at the discretion of their healthcare provider, with documentation of consent in the patient's chart
  • CCP carries the same risks as FFP or FP24: allergic transfusion reaction, transfusion related acute lung injury, transfusion associated circulatory overload, hemolytic transfusion reaction and infectious disease transmission; no risks specific to COVID-19 have been identified (J Clin Invest 2020;130:4791)
Terminology
  • Convalescent plasma: plasma (FFP or FP24) that has been collected from a recently recovered patient for the purpose of transfusion to a currently infected or recently exposed patient
  • COVID-19: the novel coronavirus first reported in Wuhan, Hubei Province, China in 2019
  • SARS-CoV-2: severe acute respiratory syndrome coronavirus 2 (synonymous with COVID-19)
  • CCP: convalescent plasma specifically for COVID-19
  • FFP: plasma frozen less than 8 hours from collection
  • FP24: plasma frozen less than 24 hours from collection
  • PCR: polymerase chain reaction
  • DHQ: donor health questionnaire
  • EUA: emergency use authorization
  • EAP: expanded access protocol
  • eIND: emergency investigational new drug authorization
  • FDA: Food and Drug Administration
  • TACO: transfusion associated circulatory overload
  • TRALI: transfusion related acute lung injury
Pathophysiology
Clinical features
Transmission
  • COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an enveloped, positive stranded RNA virus that is adapted to infect many animals, including humans
  • Transmission is primarily airborne, person to person via respiratory droplets; evidence is most suggestive of short range exposure (< 6 feet), via contact with an infected person (e.g. handshake) or touching a contaminated surface (fomite transmission, e.g. doorknob)
  • Risk factors for airborne transmission include prolonged time in an enclosed space with an infected person, especially with shouting or singing, and inadequate air ventilation (Emerg Infect Dis 2020;26:1343)
  • Reference: CDC: Scientific Brief - SARS-CoV-2 and Potential Airborne Transmission [Accessed 26 October 2020]
Symptoms
Blood donor screening
  • CCP donors must have:
    • Previous symptoms consistent with COVID-19
    • Either a positive COVID-19 PCR nasopharyngeal swab or positive antibody test (antibody testing can be confirmed on a sample collected with the plasma)
    • Symptom free for 14 days
    • Be eligible for blood donation via all standard criteria required by the FDA (FDA: Blood & Blood Products [Accessed 18 November 2020])
    • Asymptomatic individuals can be eligible to donate if they have positive antibody tests on 2 different platforms approved / cleared by the FDA (i.e. incidentally discovered during routine blood donation)
    • Regular blood donors are eligible to donate (whole blood, platelets, etc.) after 28 days without symptoms, regardless of testing status
  • Reference: FDA: Convalescent Plasma COVID-19 Letter of Authorization [Accessed 26 October 2020]
Blood donor testing
Donor deferral
Laboratory
  • Convalescent plasma must be stored at ≤ 18 °C and expires in 1 year from the time of collection
  • Convalescent plasma must be labeled as an investigational drug under the FDA
  • Patients should receive type compatible plasma; if type compatible is not available, incompatible plasma with a low titer of anti-A or anti-B (≤ 1:128) may be considered, although the impact of this has not been studied
  • Reference: FDA: Investigational COVID-19 Convalescent Plasma - Guidance for Industry [Accessed 2 November 2020]
Case reports
Treatment
  • Convalescent plasma has been shown to be most effective when given early (< 3 days) and with a high titer IgG dose (≥ 1:1,350) (Am J Pathol 2020;190:2290, medRxiv 2020 Aug 12 [Preprint])
  • Mayo expanded access protocol enrolled over 30,000 patients at multiple sites who received at least 1 dose of CCP; the study was closed in conjunction with the FDA's emergency use authorization
  • Standard dose is 200 mL (1 plasma unit), although this may be adjusted based on the size of the patient, whether only low titer products are available and if the patient is part of a clinical trial with alternative or repeat dosing algorithms
Sample assessment & plan
  • Assessment: 72 year old man with hypertension and hypercholesterolemia admitted with fever up to 39.1 °C, respiratory distress with oxygen saturations 90 - 92% on RA, requiring supplemental oxygen, cough and loss of taste and smell x 3 days. COVID-19 PCR positive by nasopharyngeal swab. Due to the patient's high risk category, convalescent plasma is warranted as treatment. I discussed this plan with the patient, including the risks of receiving a plasma blood product (transfusion related acute lung injury, transfusion associated circulatory overload, hemolysis, infectious disease, allergic reaction, which may be severe) and also discussed that this is still an investigational product under the FDA and thus the treatment may be ineffective or there may be risks that we have not yet identified. The patient expressed understanding of the risks and wishes to proceed with treatment.
  • Plan:
    • COVID-19 convalescent plasma 200 mL, type compatible
    • Isolation precautions
    • Type and screen, CBC with diff, CMP, PT / PTT, fibrinogen
    • Dexamathasone 6 mg daily for 10 days
    • Oxygen 2 L NC, titrate to maintain O2 saturation greater than 95%
Board review style question #1
A potential candidate for convalescent plasma presents for donation. He has a history of a confirmed positive PCR for COVID-19 performed by nasopharyngeal swab. He had mild symptoms of cough, fever and fatigue, and states his last symptoms were 13 days ago. Is he eligible to proceed with donation?

  1. No, he is not eligible to donate until he has been symptom free for 28 days
  2. No, he is not eligible because he also needs a COVID-19 antibody titer
  3. No, he is not eligible because he needs a repeat PCR to prove he is negative for COVID-19
  4. No, he is not eligible because he needs to be symptom free for 14 days
  5. Yes, he is eligible to donate
Board review style answer #1
D. No, he is not eligible until he has been symptom free for 14 days. Eligibility for donation for COVID-19 convalescent plasma (CCP) requires 1) confirmation of disease by either a positive PCR by nasopharyngeal swab or positive antibody test, 2) donor has been symptom free for 14 days and 3) must pass all other blood donor criteria established by the FDA. The FDA originally required a repeat PCR test to be negative, for eligibility but has since dropped that requirement. Blood donors who want to proceed with regular blood donation are eligible after 28 days of being symptom free, regardless of testing status.

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Reference: COVID-19 convalescent plasma
Board review style question #2
A 27 year old man, blood type A negative, positive for COVID-19 by viral PCR has been in the ICU for 34 days with BIPAP for severe respiratory distress. He has a clinical history of asthma and obesity. His family recently heard about convalescent plasma for COVID-19 (CCP) on the news and wants him to receive this therapy. The blood bank has 1 high titer (1:1,350) CCP unit available that is blood type O positive. The clinical team wants your thoughts on how to respond to the family.

  1. The patient can receive the unit because it is type compatible and he qualifies based on the severity of the disease and his preexisting conditions
  2. The patient can receive the unit but only if the anti-A titers are ≤ 1:128 due to type incompatibility; he qualifies based on the severity of the disease and his preexisting conditions
  3. The patient should not receive the unit, because of the risk of anti-A in a plasma unit
  4. The patient should not receive the unit, because he is past 72 hours of disease, so the CCP would not be effective
  5. The patient should not receive the unit, because his age and preexisting conditions do not put him in a high risk category
Board review style answer #2
B. The patient can receive the unit but only if the anti-A titers are ≤ 1:128 due to type incompatibility; he qualifies based on the severity of the disease and his preexisting conditions. This patient is very ill with COVID-19, with significant risk factors (asthma and obesity), despite his age. He would likely still benefit from convalescent plasma (based on current available data) even after the ideal 72 hour mark for transfusion. The problem is that the only available unit is not compatible with his blood type. Recall that a blood type O unit will have anti-A and anti-B in the plasma (see table). This unit is higher risk for causing a hemolytic transfusion reaction. Although it has not been studied, it is at the discretion of the provider to allow incompatible units for the patient. In this scenario, an anti-A titer of ≤ 1:128 is recommended but may vary by institution.

Blood type  Antigen on red cell  Antibody in plasma 
O None Anti-A and anti-B
A A Anti-B
B B Anti-A
AB A and B None

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