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Update: What do pharmacists need to know about convalescent plasma for COVID-19?

Introduction

Coronavirus disease 2019, better known as COVID-19, is a respiratory infectious disease that has rapidly spread throughout the world.1,2 The first few cases were recognized and reported in Wuhan, China in December 2019. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic.1-3 COVID-19 is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1,2 Most cases are considered mild (≥80%) with the remaining 14% of cases reported as serious and 5% as critical.2 Some cases (10%) require hospitalization for COVID-19 pneumonia with 10% of those cases necessitating intensive care unit (ICU) admission due to acute respiratory distress syndrome (ARDS).

At this time, remdesivir, an antiviral agent, is the only Food and Drug Administration (FDA)-approved treatment option for COVID-19.4 Remdesivir is approved in hospitalized patients (adults and children ≥12 years of age with weight ≥40 kg) who require supplemental oxygen. Although not FDA approved for COVID-19 treatment, dexamethasone has also been recommended, specifically in patients who require mechanical ventilation, as it has demonstrated improved survival in hospitalized patients who require supplemental oxygen. Other therapies under evaluation for the treatment of COVID-19 include immune-based therapies.

One potential treatment is COVID-19 convalescent plasma (herein after referred to as “convalescent plasma”), which received an FDA Emergency Use Authorization (EUA) for use in hospitalized patients on August 23, 2020 (reissued February 5, 2021).5 The EUA allows for the use of high antibody titer plasma in hospitalized patients early in the course of disease or in individuals with impaired humoral immunity. Specific tests are approved for determining antibody titer levels, and the FDA has set an acceptable cutoff for each individual test.

The Infectious Diseases Society of America (IDSA) recommends convalescent plasma in hospitalized patients in the setting of a clinical trial; though, the authors note a knowledge gap for this recommendation.2,6 The National Institutes of Health (NIH) also address convalescent plasma in their COVID-19 treatment guideline, but are unable to recommend for or against its use due to a lack of data and theoretical risks (eg, antibody-dependent enhancement of infection and transfusion-associated lung injury [TRALI]).4,7 In patients who do receive convalescent plasma, the IDSA and American Association of Blood Banks (AABB) suggest that evidence indicates the best outcomes are likely to occur when a high-titer unit of convalescent plasma is administered within 72 hours of COVID-19 diagnosis or hospital admission.8 Further considerations proposed by the IDSA and AABB address critically ill patients and those in the ICU as unlikely to benefit from convalescent plasma.

COVID-19 convalescent plasma product information

Convalescent plasma is serum collected from patients who have recovered from COVID-19 and that have produced antibodies to SARS-CoV-2.4,9-11 These antibodies exert their therapeutic effect by neutralizing the virus in the recipient.10,11 Additionally, the antibodies can activate complement and initiate antibody-dependent cellular toxicity and phagocytosis. Convalescent plasma provides short-term passive immunity as either prophylaxis or for treatment to reduce viral infectivity. Due to the large population of recovered COVID-19 patients, convalescent plasma is a readily available resource for prophylaxis or treatment.

The convalescent plasma dose and preferred timing of administration during the course of a COVID-19 infection has not been established.9 Dosing of convalescent plasma in general has been widely variable throughout the history of its use as post-exposure prophylaxis and/or treatment in several viral infections (eg, polio and Ebola), including respiratory infection outbreaks, such as the 2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and 2012 Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemic.10 Once convalescent plasma is administered, the duration of the circulating antibodies’ therapeutic effect is unclear and depends on the amount of antibody given, but may last weeks to months.10,11 Table 1 provides additional characteristics of COVID-19 convalescent plasma.

Table 1. COVID-19 convalescent plasma characteristics.5,9,10,12
Product Characteristics
  • Available as FFP and FP24

  • Shelf life is 1 year frozen or 5 days after thawing
Product Dose
  • Only high antibody titer plasma can be used

  • No universal dose established; EUA states that a starting dose of 1 unit (~200 mL) can be considered with additional doses based on clinical judgment

  • Patients with heart failure or cardiac dysfunction may require smaller doses or longer infusion times

  • Transfusion of 1 to 2.5 units (~200 to 500 mL) has been reported in literature

  • Some clinical trials are planning doses of 1 unit for post-exposure prophylaxis and 1-2 units for treatment
Abbreviations: EUA=Emergency Use Authorization; FFP=fresh frozen plasma; FP24=plasma frozen within 24 hours of phlebotomy

Review of COVID-19 convalescent plasma studies for the treatment of COVID-19

At this time, the efficacy and safety of COVID-19 convalescent plasma are still under investigation.2,4,9,13 Most of the available data consists of small observational studies. Mortality data from multiple randomized trials and several larger cohort studies have been published (Table 2).14-26 Much of the literature is limited by lack of control groups, variable doses and antibody titers of transfused convalescent plasma, and administration of several other concurrent therapies, which complicate the determination of convalescent plasma’s true effect in COVID-19.15,22,25,27-38

Numerous randomized controlled trials (RCTs) with convalescent plasma are underway in the United States and internationally.9 Several RCTs were terminated early, including a study in China that was underpowered due to decreasing new cases of COVID-19 and a study in the Netherlands that found high virus neutralizing antibody titers at baseline that were comparable to the titers of the donors.17,34,39 None of the larger published RCTs have found a significant mortality benefit with convalescent plasma.16,18

A Cochrane living systematic review of 2 controlled studies (n=189) concluded that effectiveness of convalescent plasma in decreasing mortality among hospitalized COVID-19 patients was uncertain based on inconsistentencies in the reported results.40 The review further reported that convalescent plasma has little to no difference in clinical symptom improvement at 7 days; however, an improvement in clinical symptoms at 15 and 30 days has been suggested based on low-certainty evidence. A meta-analysis by Sarkar et al, which included the 2 RCTs that were stopped early, found that convalescent plasma significantly reduced mortality and increased viral clearance, although the authors noted that the derived evidence was of low quality.15 Similarly, an analysis of aggregated patient data (n=4,113) from 12 controlled studies found a mortality rate of 10% in patients who received convalescent plasma for severe or life-threatening COVID-19 and 22% in patients who did not receive convalescent plasma (odds ratio [OR], 0.43; p<0.001).24 Another analysis of aggregated outcome data from 10,436 patients in 38 studies or case reports found no effect of convalescent plasma on mortality (OR, 0.58; 95% confidence interval [CI], 0.29 to 1.15; p=0.12).14 However, when the analysis was repeated without an RCT that used convalescent plasma with low antibody levels, there was a difference in mortality between patients who did and did not receive convalescent plasma (10% vs 21%; OR, 0.43; 95% CI, 0.22 to 0.84; p=0.01).

The Mayo Clinic’s Expanded Access Program cohort study (released prior to peer review on a pre-print server) found that factors such as high antibody titers and an earlier time to transfusion of convalescent plasma were associated with lower rates of 7- and 30-day mortality.27 Similar trends were reported in the case-control study by Salazar et al.22 In Mayo Clinic’s study, the high antibody titer convalescent plasma resulted in a pooled relative risk of 0.65 (95% CI, 0.47 to 0.92) for 7-day mortality and 0.77 (95% CI, 0.63 to 0.94) for 30-day mortality compared to low antibody titer convalescent plasma.27,41 An additional Kaplan-Meier survival analysis reported by the FDA found significantly improved survival in non-intubated patients (p=0.032) and even further survival benefit in a subgroup of non-intubated patients less than 80 years of age who received convalescent plasma within 3 days of COVID-19 diagnosis (p=0.0081).5 However, applicability of these findings is limited by the cohort study design, including lack of a traditional placebo control arm and the likely presence of confounders.27

Table 2. Selected literature for treatment of COVID-19 with convalescent plasma.14-26
Article
Interventions
Outcomes
Meta-analyses
Klassen et al. (2020)14

Meta-analysis of 18 trials (5 RCTs, 13 matched-control studies, and 20 case series or case reports) in 10,436 patients with severe or life-threatening COVID-19

Convalescent plasma group (n=3,145)
  • Details regarding convalescent plasma therapy and standard treatment not provided

Control groups (n=7,447)
Mortality
  • In RCTs and matched-control studies, patients who received convalescent plasma had lower mortality compared to patients who received standard treatments (19% vs 29% mortality; OR, 0.49; 95% CI, 0.37 to 0.64; p<0.001)

  • Overall, results favored the efficacy of convalescent plasma in decreasing mortality in COVID-19 patients
Sarkar et al. (2020)15

Meta-analysis of 7 trials (2 RCTs, 5 cohort studies) in 5,444 patients
Convalescent plasma group (n not specified)
  • Variable doses and antibody titers of convalescent plasma transfused

  • Some studies specify a variety of concomitant therapies given

Control groups not specified

Safety
  • 2 studies reported no AEs, 1 study reported <1% of serious AEs (eg, TACO [n=7], TRALI [n=11], and severe allergic reactions [n=3]), 1 study reported TRALI (n=1) and rash (n=1), and 1 study reported rash (n=1) (no details were provided for the remaining 2 studies)

Clinical
  • Convalescent plasma resulted in clinical improvement compared to patients that did not receive convalescent plasma (p=NS)

Mortality
  • Convalescent plasma reduced mortality risk (OR, 0.44; 95% CI, 0.25 to 0.77; I2=0%)

SARS-CoV-2 RNA
  • Convalescent plasma increased viral clearance (OR, 11.29; 95% CI, 4.9 to 25.9; I2=0%)
Randomized trials
Agarwal et al. (2020)16

Open-label, parallel arm, phase II, multicentre, RCT of 464 patients with moderate COVID-19 in India

Convalescent plasma group (n=235)
  • 2 transfusions of COVID-19 convalescent plasma 200 mL transfused 24 hours apart

  • Standard treatment: antiviralsa, broad spectrum antibiotics, immunomodulatorsb, and supportive managementc

Control group (n=229)
  • Standard treatment as described in the convalescent plasma group

Safety
  • AE: pain at the infusion site (n=1), chills (n=1), nausea (n=1), bradycardia (n=1), dizziness (n=1), dyspnea (n=2), and blockage of intravenous catheter (n=2) reported within 6 hours of convalescent plasma transfusion

Clinical
  • Convalescent plasma treatment was associated with an earlier resolution of shortness of breath and fatigue by day 7 vs control group (shortness of breath risk ratio 1.16; 95% CI, 1.02 to 1.32; fatigue risk ratio 1.21; 95% CI, 1.02 to 1.42)

  • Progression to severe disease was recorded in 17 patients in each arm (risk ratio 1.04; 95% CI, 0.54 to 1. 98)

Mortality
  • All-cause mortality at 28 days was 15% in the convalescent plasma group vs 14% in the control group (risk ratio 1.04; 95% CI, 0.66 to 1.63)

SARS-CoV-2 RNA
  • A higher proportion of patients in the convalescent plasma group had a negative conversion of SARS-CoV-2 RNA by day 3 (43% vs 37% in control arm; risk ratio 1.16; 95% CI, 1.02 to 1.32) and by day 7 (68% vs 55% in control arm; risk ratio 1.2; 95% CI, 1.04 to 1.5)
Li et al. (2020)17

Open-label, multicenter, RCT of 103 patients with severe or life-threatening COVID-19 in China
Convalescent plasma group (n=52)
  • 1 transfusion of COVID-19 convalescent plasma 200 mL (median dose; S-RBD-specific IgG titer of ≥1:640) received 30 days (median) after symptom onset

  • Standard treatment: antiviral agentsd, antibiotics, glucocorticoids, immunoglobulin, Chinese herbal medicines, antifungals, and/or interferon

Control group (n=51)
  • Standard treatment as described in the convalescent plasma group

Safety
  • AEs: chills and rash (n=1) within 2 hours of transfusion and shortness of breath, cyanosis, and severe dyspnea (n=1) within 6 hours of transfusion

Clinical
  • 51.9% of the convalescent plasma group vs 43.1% of the control group had clinical improvement within 28 days (p=NS)

  • 51% of the convalescent plasma group vs 36% of the control group were discharged by day 28 following randomization (p=NS)

Mortality
  • Mortality at 28 days was 15.7% in the convalescent plasma group vs 24% in the control group (p=NS)

SARS-CoV-2 RNA
  • 87.2% of the convalescent plasma group vs 37.5% of the control group had a negative viral PCR at 72 hours (OR, 11.39; 95% CI, 3.91 to 33.18; p<0.001)
Simonovich et al. (2020)18

Double-blind, placebo-controlled, multicenter RCT of 334 patients with severe COVID-19 in Argentina
Convalescent plasma group (n=228)
  • 1 transfusion of COVID-19 convalescent plasma (median titer of 1:3200 of total SARS-CoV-2 antibodies)

  • Patients were allowed to receive antiviral agents, glucocorticoids, or both, according to the standard of care at the institution

Control group (n=105)
  • 1 transfusion of placebo (ie, 0.9% sodium chloride)

  • Standard of treatment allowed as described in the convalescent plasma group

Safety
  • No significant differences were found between the 2 groups in the incidence of AE (OR, 1.21; 95% CI, 0.74 to 1.95)

Clinical
  • No significant difference noted between the convalescent plasma group and the placebo group in clinical outcomes at day 7 (OR, 0.88; 95% CI, 0.58 to 1.34), day 14 (OR, 1.00; 95% CI, 0.5 to 1.55), or day 30 (OR, 0.83; 95% CI, 0.52 to 1.35; p=0.46)

  • Average time from enrollment to hospital discharge was 13 days in the convalescent plasma group and 12 days in the placebo group (subhazard ratio, 0.99; 95% CI, 0.75 to 1.32)

Mortality
  • Mortality at 30 days was 10.96% in the convalescent plasma group and 11.43% in the placebo group (risk difference -0.46; 95% CI, -7.8 to 6.8)

SARS-CoV-2 RNA
  • No differences in antibody titers were noted at days 7 or 14 between the 2 groups
Nonrandomized trials
Altuntas et al. (2020)19

Retrospective case-control study of 1,776 patients with severe COVID-19 in Turkey

Convalescent plasma group (n=888)
  • Antiviral medictions included favipravir, lopinavir + ritonavir, hydroxychloroquine, and/or azithromycin

Control group (n=888)
  • Antiviral medications as described in convalescent plasma group, with the additional option of high dose vitamin C

Clinical
  • Duration of hospital stay was similar across both groups (p=0.860)

  • Duration in the ICU, rate of mechanical ventilation support and vasopressor support were significantly lower in the convalescent plasma group (p=0.001; p=0.02; p=0.001, respectively)

Mortality
  • Case fatality rate was 24.7% in the convalescent plasma group vs 27.7% in the control group (p=0.150)
Rogers et al. (2020)20

Matched cohort study of 241 patients with severe COVID-19 in the U.S.
Convalescent plasma group (n=64)
  • 2 units of COVID-19 convalescent plasma given at a median of 7 days after symptom onset

  • Testing after transfusion revealed that 13 units did not have adequate antibody levels

  • Other treatments included remdesivir and corticosteroids

Control group (n=177)
  • Other treatments as described in convalescent plasma group

Mortality
  • All-cause in-hospital mortality at day 28 was 12.5% in the convalescent plasma group and 15.8% in the control group (hazard ratio, 0.93; 95% CI, 0.39 to 2.20)

Clinical
  • Time to hospital discharge at day 28 was 8 days in both groups (p=NS)

  • Patients aged ≥65 years had a higher rate of hospital discharge after receipt of convalescent plasma vs the control group (rate ratio, 1.86, 95% CI, 1.03 to 3.36)

Safety
  • 2 cases of TRALI and 1 case of TACO were reported
Yoon et al. (2020)21

Cohort-control (propensity-matched) study of 348 patients with severe COVID-19 in the U.S.
Convalescent plasma group (n=90)
  • 1 transfusion of COVID-19 convalescent plasma ~200 mL (anti-RBD IgG titer range: <1:21,870 to ≥1:65,610)

  • Most patients received corticosteroids (91.8%) and therapeutic anticoagulation (76.7%)

Control group (n=258)
  • Most patients received corticosteroids (87.7%) and therapeutic anticoagulation (64.4%)

Mortality
  • All-cause mortality at 28 days was similar in both groups overall (OR, 0.74; 95% CI, 0.37 to 1.46; p=0.37)

  • Patients <65 years of age who received convalescent plasma had lower mortality at day 28 vs controls (OR, 0.23; 95% CI, 0.05 to 0.95; p=0.04), but there was no difference among patients ≥65 years of age (p=0.89)

  • Multivariate analysis did not reveal any difference in outcomes between the groups

Safety
  • No AEs were observed
Salazar et al. (2020)22,23

Case-control (propensity-matched) study of 351 hospitalized patients in the U.S.
Convalescent plasma group (n=143)
  • 1-2 transfusions of COVID-19 convalescent plasma (anti-RBD IgG titer range: <1:150 to ≥1:1350)

  • Other medications: steroids, azithromycin, hydroxychloroquine, antiviral therapye, and/or tocilizumab

Control group (n=173)
  • Other medications described in the convalescent plasma group

Mortality
  • Mortality at 28 days was 3.7% in the convalescent plasma group vs 7.6% in the control group (p=NS)

  • Decreased 28-day mortality rates were seen in patients that received convalescent plasma transfusion within 72 hours of admission vs the control group (1.8% and 6.3%; respectively; p=NS) and in patients that received transfusion with high titer (≥1:1350) convalescent plasma within 72 hours of admission vs the control group (1.2% vs 7%; p=NS)

  • Mortality at 60 days was 6.2% in the convalescent plasma group vs 10.3% in the control group (p=0.003)

  • Decreased 60-day mortality rates were seen in patients that received transfusion with high titer (>1:1350) convalescent plasma within 72 h of admission vs the control group (5.7% vs 10.7%; p=0.03)
Joyner et al. (2020)24

Uncontrolled cohort study of 35,322 hospitalized patients in the U.S.
  • Transfusion of ≥1 unit of COVID-19 convalescent plasma ~200 mL

  • Other medications: ARB, ACE-inhibitor, azithromycin, remdesivir, steroids, chloroquine, and/or hydroxychloroquine

Mortality
  • 7-day mortality rate was 8.7% (95% CI, 8.3% to 9.2%) in patients transfused within 3 days of COVID-19 diagnosis vs 11.9% (95% CI, 11.4% to 12.3%) in patients transfused within ≥4 days of diagnosis (p<0.0001)

  • 7-day mortality rate was 13.7% (95% CI, 11.1% to 16.8%) in patients transfused with a low antibody titerf, 11.6% (95% CI, 10.3% to 13.1%) in patients transfused with a medium antibody titerg, and 8.9% (95% CI, 6.8% to 11.7%) in patients transfused with a high antibody titerh (p=0.048)

  • 30-day mortality rate was 21.6% (95% CI, 21% to 22.3%) in patients transfused within 3 days of diagnosis vs 26.7% (95% CI, 26.1% to 27.3%) in patients transfused within ≥4 days of diagnosis (p<0.0001)

  • 30-day mortality rate was 29.6% (95% CI, 26% to 33.5%) in patients transfused with a low antibody titerf, 27.4% (95% CI, 25.5% to 29.4%) in patients transfused with a medium antibody titerg, and 22.3% (95% CI, 18.9% to 26.1%) in patients transfused with a high antibody titerh (p=0.028)
Xia et al. (2020)25

Uncontrolled, cohort study of 1,568 patients with severe COVID-19 in China
Convalescent plasma group (n=138)
  • 1 transfusion of COVID-19 convalescent plasma 200 to 1200 mL received 45 days (median) from symptom onset

Standard treatment group (n=1430)
Safety
  • No serious AEs were reported; 3 patients had minor allergic reactions

Clinical
  • ICU admission rate was 2.4% in the convalescent plasma group vs. 5.1% in the standard treatment group (p-value not reported)

  • Within 14 days, 80% of patients in the convalescent plasma group no longer had detectable viral levels

  • Among patients with clinical improvement within 8 weeks, median time to clinical improvement was about 10 days

Mortality
  • At the end of the study period, mortality was 2.2% in the convalescent plasma group and 4.1% in the standard treatment group (p-value not reported)
Joyner et al. (2020)26

Uncontrolled, cohort study of 5,000 patients with severe COVID-19 in the U.S.
  • Tranfusion of COVID-19 convalescent plasma 200 to 500 mL

Safety
  • Serious AEs within 4 hours post-transfusion were reported in <1% of all transfusions

  • Serious AEs: TACO (n=7), TRALI (n=11), and severe allergic transfusion reactions (n=3)

Mortality
  • Mortality rate at day 7 was 14.9%
Abbreviations: ACE=angiotensin-converting enzyme; AE=adverse event; ARB=angiotensin receptor blocker; CI=confidence interval; COVID-19=coronavirus disease 2019; I2=statistical heterogeneity; ICU=intensive care unit; NS=non-significant; OR=odds ratio; PCR=polymerase chain reaction; RBD=receptor binding domain; RCT=randomized controlled trial; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; S/Co=signal-to-cut-off ratio; TACO=transfusion-associated circulatory overload; TRALI=transfusion-related acute lung injury
aHydroxychloroquine, remdesivir, lopinavir/ritonavir, oseltamivir
bSteroids, tocilizumab
cOxygen through a nasal cannula, face mask, non-rebreathing face mask; non-invasive or invasive mechanical ventilation; awake proning
dLopinavir/ritonavir, oseltamivir, umifenovir (not available in the U.S.), ribavirin, and other antivirals
eLopinavir/ritonavir, remdesivir, and ribavirin
fIgG <4.62 S/Co
gIgG=4.62 to 18.45 S/Co
hIgG >18.45 S/Co

Safety concerns of COVID-19 convalescent plasma

Convalescent plasma transfusion has several theoretical risks based on known risks associated with standard plasma transfusions that are therefore not unique to this specific product (Table 3).4,9-11,41 These potential adverse effects have not been fully established for COVID-19 convalescent plasma.9 The historical data from SARS and MERS suggest that convalescent plasma use in coronavirus infections is potentially safe, although 2 case reports of possible convalescent plasma-induced TRALI events have been described in a patient with Ebola and a patient with MERS.10,11,41-43 Possible transfusion-related adverse events that resolved with corticosteroid treatment were reported in 2 patients in the RCT by Li et al.17

Joyner et al conducted a safety analysis of 20,000 patients in the Mayo Clinic Expanded Access Program cohort and also found a low incidence (n=146; <1%) of serious adverse events within 4 hours of transfusion, which included 83 nonfatal reports of transfusion-associated circulatory overload (TACO) (n=37), TRALI (n=20), and severe allergic reactions (n=26).44 Of the 146 transfusion-related serious adverse events, 63 deaths (0.3% of all transfusions) occurred, with 13 deaths deemed as possibly (n=12) or probably (n=1) related to convalescent plasma treatment.  Additional serious adverse events reported within 7 days of the transfusion included thrombotic/thromboembolic events (n=87), cardiac events (n=643) and sustained hypotensive events requiring vasopressors (n=406); the majority of these complications were deemed unrelated to convalescent plasma treatment. Additionally, Joyner et al reported limited cases of TACO, TRALI, and severe allergic reactions in an earlier safety analysis of 5,000 patients, and no significant adverse events were reported in most of the COVID-19 studies or in several previous SARS-associated coronavirus and severe influenza studies.14,27,29-35,37,45

Table 3. Potential adverse effects of convalescent plasma transfusions.4,9-11,41
  • Allergic reactions

  • Transfusion-associated circulatory overload (TACO)

  • Transfusion-associated acute lung injury (TRALI)

  • Antibody-dependent enhancement of infection

  • Transmission of infectious agents (rare)

  • Red blood cell alloimmunization (rare)

Access to COVID-19 convalescent plasma in the United States

Prior to the recent EUA, access to COVID-19 convalescent plasma was restricted to 3 pathways: clinical trials, an expanded access investigational new drug (IND) application, or a single patient emergency investigational new drug (eIND) application.46 Mayo Clinic was the leading institution collecting and providing COVID-19 convalescent plasma for the National Expanded Access Program, which was discontinued on August 28, 2020 after more than 75,000 patients were treated.47

Under the EUA, any FDA-registered or licensed blood establishment can now collect or distribute convalescent plasma according to institutional protocols.13 The EUA request document includes information about convalescent plasma collection, labeling, storage, antibody testing, and adverse event monitoring. Clinicians are required to provide recipients with written information about the potential benefits and risks of convalescent plasma via the FDA’s official patient fact-sheet (available at: https://www.fda.gov/media/141479/download).

COVID-19 convalescent plasma donation

Convalescent plasma can be donated at blood donation centers or through the American Red Cross.48,49 Blood donation centers can be located through the AABB website.50 One donor of COVID-19 convalescent plasma is estimated to provide enough plasma to treat 2 to 3 patients.51 As of August 2020, the American Red Cross has distributed 32,000 units of convalescent plasma from more than 14,000 donors, but the supply has not been adequate to meet the demand.52 Consequently, the FDA and other medical organizations have launched promotional campaigns to raise public awareness about the need and opportunity for plasma donation.48,53 To meet eligibility for COVID-19 convalescent plasma donation, the FDA has set forth certain criteria (Table 4).9,13,46

Table 4. COVID-19 convalescent plasma donor eligibility criteria.9,13,46
  • Lab confirmed COVID-19 by 1 of the following:
    • Diagnostic test (eg, nasopharyngeal swab) at time of illness

    • (+) SARS-CoV-2 antibodies after recovery using 2 different tests

  • Complete resolution of symptoms for ≥14 days

  • Previously pregnant female donors must have (-) HLA antibodies tested since most recent pregnancy

  • If available, SARS-CoV-2 neutralizing antibody titers of ≥1:160 (1:80 is an acceptable alternative)
Abbreviations: COVID-19=coronavirus disease 2019; HLA=human leukocyte antigen; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2

Conclusions

COVID-19 convalescent plasma is an emerging treatment that has shown potential benefit in observational or uncontrolled studies. Randomized trials have not shown a mortality benefit, but this may be due to lack of statistical power since several meta-analyses have reported significantly improved mortality with this therapy. The FDA has authorized the use of convalescent plasma with high antibody titers in the United States under an EUA, but it is not considered an FDA-approved product. The findings of ongoing RCTs are needed to establish efficacy and safety. Knowledge gaps that will hopefully be addressed by forthcoming studies include definitive effects on mortality and other clinical outcomes, efficacy in children and pregnant women, long-term effects, efficacy in patients with mild disease, and potential for use as prophylaxis.

References

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  8. Clarifying the emergency use authorization framework for COVID-19 convalescent plasma: considerations for clinicians prepared jointly by the Infectious Diseases Society of America and AABB. Updated November 18, 2020. Accessed January 18, 2021. https://www.idsociety.org/globalassets/covid-19-real-time-learning-network/therapeutics-and-interventions/convalescent-plasma/aabb-idsa-convalescent-plasma-eua–final.pdf
  9. Assessment of evidence for COVID-19-related treatments. American Society of Health-System Pharmacists. Updated January 14, 2021. Accessed January 20, 2021. https://www.ashp.org/-/media/assets/pharmacy-practice/resource-centers/Coronavirus/docs/ASHP-COVID-19-Evidence-Table.ashx
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Katie Miles, PharmD, Clinical Assistant Professor
Paula Krzos, PharmD Candidate
Heather Ipema, PharmD, BCPS, Clinical Assistant Professor
University of Illinois at Chicago College of Pharmacy

February 2021

The information presented is current as of January 20, 2021. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.