Abstract
BACKGROUND:
The safety of transfusion of SARS-CoV-2 antibodies in high plasma volume blood components to recipients without COVID-19 is not established. We assessed whether transfusion of plasma or platelet products during periods of increasing prevalence of blood donor SARS-CoV-2 infection and vaccination was associated with differences in outcomes in hospitalized patients without COVID-19.
METHODS:
We conducted a retrospective cohort study of hospitalized adults who received plasma or platelet transfusions at 21 hospitals during pre-COVID-19 (3/1/2018–2/29/2020), COVID-19 pre-vaccine (3/1/2020–2/28/2021), and COVID-19 post-vaccine (3/1/2021–8/31/2022) study periods. We used multivariable logistic regression with generalized estimating equations to adjust for demographics and comorbidities to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS:
Among 21,750 hospitalizations of 18,584 transfusion recipients without COVID-19, there were 697 post-transfusion thrombotic events, and oxygen requirements were increased in 1,751 hospitalizations. Intensive care unit length of stay (n=11,683) was 3 days (interquartile range 1–5), hospital mortality occurred in 3,223 (14.8%), and 30-day rehospitalization in 4,144 (23.7%). Comparing the pre-COVID, pre-vaccine and post-vaccine study periods, there were no trends in thromboses (OR 0.9 [95% CI 0.8, 1.1]; p=0.22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p=0.41). In parallel, there were no trends across study periods for ICU length of stay (p=0.83), adjusted hospital mortality (OR 1.0 [95% CI 0.9–1.0]; p=0.36), or 30-day rehospitalization (p=0.29).
DISCUSSION:
Transfusion of plasma and platelet blood components collected during the pre-vaccine and post-vaccine periods of the COVID-19 pandemic was not associated with increased adverse outcomes in transfusion recipients without COVID-19.
INTRODUCTION
Multiple randomized clinical trials have examined the safety and efficacy of COVID-19 convalescent plasma (CCP) in preventing severe COVID-19 or death.1–3 Although uncommon, adverse outcomes were reported in COVID-19 recipients of convalescent plasma and were hypothesized to be related to transfused autoantibodies in CCP units.4,5 Autoantibodies have been associated with intensive care unit (ICU) admission and death in COVID-19 patients and have been identified in CCP units.6,7 While there is significant data supporting the overall safety of CCP, there is no safety evidence regarding the transfusion of these products to recipients without COVID-19.8,9 Adding to these concerns, dramatic boosting of SARS-CoV-2 antibody levels occurs in donors with previous SARS-CoV-2 infections who were vaccinated compared to those who were infected but not vaccinated.7
Nationally, a significant rise in the prevalence of SARS-CoV-2 antibodies was recognized in the blood donor population as a byproduct of SARS-CoV-2 infection and vaccination.10–13 In the United States, infection-induced SARS-CoV-2 seroprevalence in blood donors increased from 11% to 70% from December 2020 to September 2022.11,13 In parallel, combined infection- and vaccination-induced SARS-CoV-2 donor seroprevalence was estimated to be 96% by September 2022.12,13 Neutralizing and anti-spike antibodies in blood donors are known to increase by several logs following subsequent exposure to novel SARS-CoV-2 variants or vaccine boosting.14,15 Elevations of antibodies following SARS-CoV-2 infection or vaccination may include a concomitant rise in autoantibodies associated with adverse events in COVID-19 patients.16,17 In parallel to patients treated with CCP, passive transfer of donor SARS-CoV-2 antibodies is recognized to occur in transfusion recipients without COVID-19, including recipients of platelet products.18 Transfusion of SARS-CoV-2 antibodies or autoantibodies in high plasma volume blood components may impact outcomes in recipients without COVID-19, and the receipt of blood from previously infected or vaccinated blood donors has been a concern raised by some patient advocacy groups and even lawmakers.19,20
In addition to prolonged hospitalization and death, pulmonary edema and thromboses have separately been associated with severe COVID-19 and blood transfusion.21–23 In this observational study, we assessed whether transfusion of plasma or plasma-rich platelet products collected during periods of increasing prevalence of blood donor SARS-CoV-2 infection and/or vaccination were associated with changes in rates of thrombotic or pulmonary events, ICU length of stay, hospital mortality, and rehospitalization in transfusion recipients without COVID-19.
METHODS:
Design Overview:
We conducted a retrospective cohort study using electronic health record (EHR) data from Kaiser Permanente Northern California (KPNC), which serves a population of 4.6 million members. We included all hospitalized adult, non-obstetric KPNC patients who were transfused plasma or platelet products in 21 hospitals during a 4.5-year period from March 1, 2018 through August 31, 2022. Data were divided into “pre-COVID” (3/1/2018 through 2/29/2020), COVID-19 “pre-vaccine” (3/1/2020 through 2/28/2021), and COVID-19 “post-vaccine” (3/1/2021 through 8/31/2022) study periods based on blood donor SARS-CoV-2 epidemiology and antibody testing results.10–13 Transfused patients were grouped as recipients of only-plasma blood components, only-platelet components, or both plasma and platelet components given the distinct epidemiology of transfusion indications for these components.24,25 Patients were allowed to contribute multiple hospital episodes if they were transfused plasma or platelet units during more than one hospitalization. All KPNC patients who were hospitalized during the COVID-19 pandemic were tested for SARS-CoV-2 by nasal swab polymerase chain reaction, and we excluded subjects with a positive result within 90 days prior to hospitalization. Patients with a history of thrombosis or prior anticoagulation, or those who already required increased levels of respiratory support (i.e., more than the use of a nasal cannula) prior to transfusion were excluded from analysis of thrombosis and respiratory outcomes, respectively. The KPNC Institutional Review Board approved this study.
Exposures:
Transfusion of plasma and platelet blood components during hospitalization during the pre-COVID-19, COVID-19 pre-vaccine, and COVID-19 post-vaccine study periods.
Outcomes:
Post-transfusion arterial or venous thrombosis, maximal level of respiratory support, ICU length of stay, hospital mortality, and 30-day rehospitalization.
The incidence of arterial and venous thromboses after plasma or platelet transfusion was defined using the combination of diagnosis codes and timing of new anticoagulant administration following transfusion.26,27 We categorized the maximal level of respiratory support using mutually exclusive, hierarchical categories (room air, nasal cannula, high flow oxygen, noninvasive ventilation, invasive ventilation). Maximal level of respiratory support was assessed prior to index transfusion and daily thereafter. We defined increased level of respiratory support as the need for greater oxygen than delivered by nasal cannula 24 to 48 hours following index plasma or platelet transfusion.
Covariates:
We considered individual-level factors, including sex, age, body mass index, comorbidities and SARS-CoV-2 vaccination status. We classified patients as having emergency or elective admission based on whether they were admitted through the emergency department. We classified hospitalizations as surgical admissions based upon the occurrence of surgical procedural codes during hospitalization.28 We quantified comorbid disease burden using the COPS2 (Comorbidity Points Score, version 2), which is based upon patients’ medical diagnoses within the 12 months preceding hospitalization.28–30 We quantified severity of illness at admission with the LAPS2 (Laboratory Acute Physiology Score, version 2), which is based on laboratory test results, vital signs, and neurologic status within 72 hours prior to hospital entry.29 SARS-CoV-2 vaccination status of transfusion recipients was obtained from the KPNC EHR and California state immunization records. Concomitant transfusion of red blood cell components was analyzed as a covariate in models.
Statistical Analysis:
Descriptive analyses are presented as counts and percentages, medians, and interquartile ranges (IQRs), or proportions. Accordingly, we used chi-square tests for equal proportion or Wilcoxon rank sum tests to test differences. We examined trends in thromboses, oxygen requirements, ICU length of stay, and mortality for all patients and for subsets of plasma-only, platelet-only, or both plasma and platelet recipients across the pre-COVID, pre-vaccine, and post-vaccine study periods. In addition, we examined ICU length of stay and rates of 30-day re-hospitalization among patients who survived to hospital discharge. For thrombosis and respiratory outcomes, we examined patient outcomes in subgroups based upon age, sex, emergency or elective surgical or medical status, and SARS-CoV-2 vaccination status.
Using the above covariates, we constructed multivariable regression models with thrombosis, increased respiratory support, and hospital mortality as dependent variables. We used logistic regression via generalized estimating equation (GEE) with exchangeable working correlation structure to account for repeated within-individual observations and included study period as a covariate to test for trends. We reported results for dichotomous outcomes as adjusted odds ratios (OR’s) with corresponding 95% confidence intervals (CI).
Statistical significance was indicated by the 95% CI not containing the null or two-sided p-values less than 0.05. Statistical analyses were performed using Stata Version 14.2 and SAS version 9.4.
Role of the funding source
The study sponsor collaborated on the study design and had no role in data collection, data analysis, data interpretation, or preparation of the manuscript. The REDS-IV-P publications committee reviewed the manuscript and approved its submission for publication.
RESULTS:
Patient characteristics and outcomes
From 2018 to 2022 there were 21,750 hospitalizations of 18,584 patients in which patients were transfused plasma or platelet products. The 21,750 hospitalizations were divided into 10,310 pre-COVID, 4,580 pre-vaccine, and 6,860 post-vaccine study periods based on US blood donor SARS-CoV-2 antibody testing results (Figure 1), which mirrored the COVID-19 vaccination and mortality rates in the general United States population (Appendix Figure 1).10–13 Among these 21,750 hospitalizations, 10,317 hospitalizations involved transfusion of only platelet components, 7,676 involved only plasma components, and 3,757 involved both platelet and plasma components (Figure 2).
Figure 1:
Estimate of SARS-CoV-2 seroprevalence and infections among blood donors by study period
Data presented with permission from the National Blood Donor Seroprevalence Study (https://data.cdc.gov/Laboratory-Surveillance/2020-2021-Nationwide-Blood-Donor-Seroprevalence-Su/mtc3-kq6r). The blue line shows the weighted seroprevalence of the blood donor population with both SARS-CoV-2 spike and nucleocapsid antibodies, representing the proportion of the population with antibodies from infection. The red line shows the weighted SARS-CoV-2 spike antibody seroprevalence, representing the proportion of the donor population with antibodies from infection and/or vaccination.
Figure 2:
Flow Diagram for number of hospitalizations by outcome and transfusion exposure
Number of hospitalizations by outcome (thrombosis, oxygen requirement, intensive care unit length of stay, and 30-day rehospitalization) and transfused component type during hospitalization (plasma-only transfusion, platelet-only transfusion, or transfusion both plasma and platelet components)
Abbreviation: Tx, transfusion
Baseline recipient characteristics are presented in Table 1. The mean recipient age at the time of hospitalization was 66 years (standard deviation [SD], 16 years), and 42.6% of recipients (n=9,273) were female. The median number of hospitalizations per patient was 1 (IQR 1–1), 80.9% (n=17,590) were emergency admissions, and 37.0% (n=8,057) of hospitalizations were surgical.
Table 1:
Hospitalization characteristics
| Pre-COVID n=10,310 | Pre-Vaccine n=4,580 | Post-Vaccine n=6,860 | |
|---|---|---|---|
| Agea | 67 ±15 | 66 ±16 | 65 ±16 |
| Male (%) | 5,880 (57) | 2,649 (58) | 3,948 (58) |
| Body mass index (IQR) | 27 (23–32) | 27 (23–32) | 27 (23–31) |
| Charlson Comorbidity Indexb | 0 (0–5) | 0 (0–5) | 0 (0–4) |
| Comorbidity Point Score 2 (COPS2)b,c | 64 (30–100) | 60 (28–97) | 59 (26–97) |
| Laboratory Acute Physiology Score 2 (LAPS2)b,d | 77 (44–114) | 83 (46–122) | 78 (36–122) |
| Emergency admission (%) | 8,390 (81) | 3,736 (82) | 5,464 (80) |
| Surgical admission (%) | 3,852 (37) | 1,633 (36) | 2,572 (37) |
| Intensive care admission (%) | 5,639 (54.6) | 2,558 (51.2) | 3,971 (54) |
| ICU length of stay (days)b | 2.8 (1.4–5.8) | 2.5 (1.2–5.5) | 2.8 (1.3–6.0) |
| Transfused plasma (%) | 5,690 (55.2) | 2,413 (53.7) | 3,330 (48.5) |
| Transfused platelets (%) | 6,341 (61.5) | 2,941 (64.2) | 4,792 (69.9) |
| Transfused both platelets and plasma (%) | 1,721 (16.7) | 774 (16.9) | 1,262 (18.4) |
| Transfused red blood cells (%) | 6,040 (58.6) | 2,813 (61.4) | 4,340 (63.2) |
| Pre-transfusion anticoagulation (%) | 1,427 (13.8) | 657 (14.3) | 1,038 (15.1) |
| Pre-transfusion thrombosis (%) | 1,166 (11.3) | 501 (10.9) | 657 (9.6) |
| Pre-transfusion oxygen requirement (%)e | 2,214 (21.5) | 1,008 (22.0) | 1,479 (21.6) |
Abbreviation: IQR, interquartile range; ICU, intensive care unit
Mean ± standard deviation
Median (interquartile range)
Longitudinal, diagnosis-based score. Association with hospital mortality rates for scores < 50 are less than 2%, while scores above 100 are associated with mortality rates of 5% or more.
Increasing degrees of physiologic derangement are reflected in a higher LAPS2. The univariate association between LAPS2 and mortality is such that mortality rates for scores < 50 are less than 1.5% while scores above 125 are associated with mortality rates of 10–15% or more.
Defined as greater than the use of oxygen delivery by nasal cannula prior to transfusion
Over the course of the study, a total of 43,021 platelet units and 37,263 plasma units were transfused. Among recipients of each component type, the median number of transfused plasma units was 2 (IQR 1–3) and the median number of transfused platelet units was 2 (IQR 1–3) (Appendix Table 1). 11,683 patients (53.7%) were admitted to the ICU, and the length of stay for these patients was 3 days (IQR 1–6). Death occurred in 3,223 (15.6%) hospitalizations, and 30-day rehospitalization occurred in 4,144 (23.7%) of hospital survivors.
Association of study period on thrombosis and oxygen requirements in transfusion recipients
Among the 21,750 hospitalizations, 5,891 (27.1%) had a history of thrombosis or were already on anticoagulation prior to transfusion (Table 1). Excluding these hospitalizations, 697 arterial and venous thromboses occurred in 15,859 hospitalizations (4.4%). Across the study periods, unadjusted trends in thrombosis outcomes (Table 2) were not changed in transfusion recipients of only plasma components (p=0.46), of only platelet components (p=0.15), and of both platelet and plasma components (p=0.09).
Table 2:
Thrombosis and oxygen requirements in hospitalizations by study period
| Study period | Pre-COVID | Pre-Vaccine | Post-Vaccine | ||||
|---|---|---|---|---|---|---|---|
| Unadjusted | Adjusted OR (95% CI) | Unadjusted | Adjusted OR (95% CI) | Unadjusted | Adjusted OR (95% CI) | P-valuea | |
| Arterial or venous thrombosis (n=15,859)b | |||||||
| All N=15,859 | 4.8% (360/7,468) | [Ref] | 4.4% (148/3,362) | 1.0 (0.8–1.2) | 3.8% (189/5,029) | 0.8 (0.6–1.1) | 0.22 |
| Plasma only N=5,108 | 3.8% (102/2,629) | [Ref] | 3.6% (39/1,097) | 0.8 (0.6–1.2) | 3.1% (43/1,382) | 0.8 (0.5–1.2) | 0.49 |
| Platelets only N=8,010 | 4.0% (145/3,599) | [Ref] | 3.9% (66/1,690) | 0.9 (0.7–1.3) | 3.1% (85/2,721) | 0.8 (0.5–1.0) | 0.72 |
| Plasma and Platelets N=2,741 | 9.1% (113/1,240) | [Ref] | 7.5% (43/576) | 1.1 (0.6–1.8) | 6.6% (61/926) | 0.7 (0.4–1.2) | 0.09 |
| Increased oxygen requirement (n=17,049)c | |||||||
| All N=17,049 | 11.0% (888/8,096) | [Ref] | 9.8% (350/3,572) | 0.8 (0.7–0.9) | 11.3% (609/5,381) | 1.0 (0.8–1.1) | 0.41 |
| Plasma only N=6,012 | 7.6% (239/3,156) | [Ref] | 7.4% (93/1,265) | 0.9 (0.7–1.1) | 8.0% (127/1,591) | 1.0 (0.8–1.2) | 0.50 |
| Platelets only N=8,513 | 7.8% (297/3,812) | [Ref] | 6.3% (112/1,777) | 0.8 (0.7–1.0) | 7.2% (209/2,824) | 0.9 (0.8–1.1) | 0.19 |
| Plasma and Platelets N=2,524 | 26.7% (301/1,128) | [Ref] | 24.9% (132/530) | 0.9 (0.7–1.1) | 27.8% (241/866) | 1.0 (0.8–1.2) | 0.78 |
Abbreviation: OR, odds ratios; CI, confidence interval
Adjusted odds ratios (aOR) with 95% confidence interval presented for oxygen requirements and thromboses in Pre-vaccine and Post-vaccine study periods relative to the Pre-COVID period adjusting for demographics and comorbidities presented in Table 1 and number of plasma, platelet, and RBC units.
P-value for unadjusted trends in thrombosis for recipients of only plasma (p=0.46); only platelets (p=0.15); both platelet and plasma components (p=0.09)
P-value for unadjusted trends in oxygen requirements for only plasma (p=0.81); only platelets (p=0.33); both platelet and plasma components (p=0.82)
Among the 21,750 hospitalizations, 21.6% (n=4,701) of patients had increased oxygen requirements prior to transfusion (Table 1). Excluding these hospitalizations, oxygen requirements were increased in 1,751 (10.2%) hospitalizations during the 24-to-48-hour period following transfusion. Across the study periods, unadjusted trends in increased oxygen requirements (Table 2) were unchanged in patients transfused only plasma components (p=0.81), only platelet components (p=0.33), and both platelet and plasma components (p=0.82).
In multivariable analysis comparing the pre-COVID, pre-vaccine, and post-vaccine study periods, there were no trends in rates of thromboses (OR 0.9 [95% CI 0.8, 1.1]; p=0.22) or oxygen requirements (OR 1.0 [95% CI 0.9, 1.1]; p=0.41). Among recipients of specific blood components, there were no adjusted trends across study periods for thromboses in patients transfused only plasma components (OR 0.9 [95% CI 0.8, 1.1]; p=0.49), only platelet components (OR 1.0 [95% CI 0.8, 1.1]; p=0.72), and both platelet and plasma components (OR 0.9 [95% CI 0.7, 1.0]; p=0.09). In parallel, there were no adjusted trends across study periods for increased oxygen requirements in patients transfused only plasma components (OR 1.0 [95% CI 0.6, 1.3]; p=0.50), transfused only platelet components (OR 0.9 [95% CI 0.9, 1.0]; p=0.19), or transfused both platelet and plasma components (OR 1.0 [95% CI 0.9, 1.1]; p=0.78).
There was no evidence of increased post-transfusion oxygen requirements or thrombotic events across study periods when examined by patient sex and age, admission category, or surgical status (Appendix Table 2). In fact, fewer thrombotic events occurred during the post-vaccine study period in several age and admission subgroups (Appendix Table 3). Across study periods, there were no significant trends in thromboses (p=0.41) or oxygen requirements (p=0.29) in unvaccinated patients transfused plasma or platelet components or when examining subgroups of transfusion recipients during the SARS-CoV-2 Omicron variant period from January through August 2022 (Appendix Table 4). In addition, we compared vaccinated and unvaccinated recipients during the post-vaccine period and found no differences in thromboses (137/3,761 [3.6%] vs. 52/1,268 [4.1%]; p=0.46) or oxygen requirements (448/4,096 [10.9%] vs. 129/1,287 [10.0%]; p=0.35).
Associations of study period on ICU length of stay and mortality in transfusion recipients
The median ICU length of stay [IQR] was similar in 11,683 transfused ICU patients (Table 3) during the pre-COVID (2.8 days [1.3–5.8]) pre-vaccine (2.8 days [1.3–6.6]) and post-vaccine study periods (2.9 [1.4–6.3]; p=0.83). This relationship did not differ when examining ICU length of stay excluding patients with a competing risk of death (p=0.57). In parallel there were no trends in ICU length of stay across study periods among ICU patients transfused only plasma components (p=0.31), only platelet components (p=0.79), or both plasma and platelet components (p=0.31).
Table 3:
Trends in intensive care length of stay, 30-day rehospitalization and mortality by study period
| Study period | Pre-COVID | Pre-Vaccine | Post-Vaccine | P-valuea |
|---|---|---|---|---|
| Intensive care length of stay in days [interquartile range] (n=11,683) | ||||
| All N=11,683 | 2.8 [1.3–5.8] | 2.8 [1.3–6.6] | 2.9 [1.4–6.3] | 0.83 |
| Plasma only N=3,344 | 2.9 [1.5–5.8] | 2.6 [1.3–5.2] | 2.9 [1.5–5.9] | 0.81 |
| Platelets only N=5,201 | 2.2 [1.2–4.7] | 2.1 [1.1–4.1] | 2.2 [1.2–4.7] | 0.79 |
| Plasma and Platelets N=3,138 | 3.6 [1.8–7.9] | 3.6 [1.8–8.0] | 3.9 [1.8–8.8] | 0.31 |
| 30-day rehospitalization (n=17,480) | ||||
| All N=17,480 | 23.6% (2,065/8,746) | 24.7% (948/3,834) | 23.1% (1,131/4,900) | 0.19 |
| Plasma only N=6,326 | 21.9% (753/3,432) | 23.3% (322/1,382) | 23.2% (351/1,512) | 0.46 |
| Platelets only N=8,623 | 25.6% (1,038/4,058) | 26.8% (512/1,924) | 24.0% (633/2,641) | 0.08 |
| Plasma and Platelets N=2,531 | 21.8% (274/1,256) | 20.8% (110/528) | 19.7% (147/747) | 0.52 |
| Hospital mortality, adjusted odds ratio [95% confidence interval] (n=21,750) | ||||
| All N=21,750 | [Ref] | 1.1 [0.9–1.2] | 1.0 [0.9–1.1] | 0.76 |
| Plasma only N=7,676 | [Ref] | 1.1 [0.9–1.3] | 1.1 [0.9–1.3] | 0.33 |
| Platelets only N=10,317 | [Ref] | 0.9 [0.7–1.3] | 0.8 [0.5–1.0] | 0.76 |
| Plasma and Platelets N=3,757 | [Ref] | 1.1 [0.6–1.8] | 0.7 [0.4–1.2] | 0.88 |
P-value for trends across study period
Adjusted odds ratios with 95% confidence interval presented for hospital mortality in Pre-vaccine and Post-vaccine study periods relative to the Pre-COVID study period adjusting for demographics and comorbidities presented in Table 1 and number of plasma, platelet, and RBC units.
There were no trends across study periods for adjusted hospital mortality (OR 1.0 [95% CI 0.9–1.0]; p=0.36) including for subsets of recipients of plasma only (OR, 1.0 [CI, 0.9 to 1.1]; p=0.62), platelet only (OR, 0.9 [CI, 0.9 to 1.0]; p=0.09), and both platelet and plasma (OR, 1.0 [CI, 0.9 to 1.1]; p=0.79) components. There were no trends across study periods for adjusted hospital mortality among unvaccinated recipients (OR, 1.0 [CI, 0.9 to 1.0]; p=0.49). Lastly, among survivors of hospitalization, there were no trends in rates of 30-day rehospitalization across study periods for all transfused recipients (p=0.29) as well as recipients of plasma-only (p=0.72), platelet-only (p=0.10) and both platelet and plasma (p=0.55) components.
DISCUSSION:
In our cohort of transfused patients, we found no trends in unadjusted or adjusted rates of thromboses or increased oxygen requirements in plasma and platelet product recipients during known periods of increasing blood donor SARS-CoV-2 infection and vaccination. We did not identify changes in ICU length of stay, adjusted hospital mortality, or rehospitalization across the study periods. Lastly, there were not worsened outcomes among subgroups of patients, including unvaccinated transfusion recipients. In sum, transfusion of plasma and platelet components collected during the pre-vaccine and post-vaccine periods of the COVID-19 pandemic was not associated with worsened outcomes in SARS-CoV-2 negative transfusion recipients.
Prior to the implementation of mitigation strategies, plasma transfusions from female donors were associated with the occurrence of transfusion-related acute lung injury (TRALI), likely through an antibody-mediated mechanism.31 With few treatments available for severe COVID-19 disease, CCP was investigated as a therapy in a series of randomized controlled clinical trials.2–5 In some clinical trials, the investigators assessed for cardiopulmonary complications of plasma transfusion, including TRALI as well as transfusion associated circulatory overload (TACO), and transfusion associated dyspnea (TAD).22 Rare adverse transfusion outcomes were identified in some COVID-19 recipients of CCP.4,5
The investigators of the CONCUR clinical trial hypothesized that elevated autoantibody titers in CCP units could be the cause of the adverse reactions. Several studies associated interferon autoantibodies in patients with COVID-19 with adverse events, such as ICU admission and death, and autoantibodies were identified in plasma components manufactured from blood donations from CCP donors.6,7,32 A subset of patients with severe COVID-19 also have anti-phospholipid antibodies and/or anti–neutrophil extracellular trap autoantibodies that may activate complement and promote thrombosis.33,34 While titers of pre-existing anti-HLA antibodies are recognized to increase in the setting of vaccination,17 recent studies have shown that SARS-CoV-2 infection but not vaccination are associated with development of new autoantibodies.35,36 Autoantibodies associated with adverse outcomes have been identified in severe COVID-19 patients; however, evidence of an effect of these antibodies on COVID-19 pathogenesis remains limited.
Recent findings from animal studies of vaccine-boosted CCP also raised concerns related to the safety of high plasma volume blood components from CCP donors. As noted, SARS-CoV-2 infection followed by vaccination of blood donors is known to result in dramatic boosting of binding and neutralizing antibodies in CCP.15 Hamsters infected with SARS-CoV-2 who were infused with pooled vaccine-boosted donor CCP (but not pooled normal titer CCP donor plasma or control plasma) developed acute kidney injury and worsened pulmonary outcomes.37
Despite these findings in animal models and clinical trials of CCP in patients with COVID-19, we found no association between exposure to plasma-containing blood products and adverse outcomes in SARS-CoV-2 negative patients during the COVID-19 pandemic. We hypothesized that patient outcomes other than mortality might be more sensitive to a potential antibody-mediated effect. We did not identify increased levels of respiratory support or rates of thrombosis following transfusion of plasma or plasma-rich platelet products when comparing study periods prior to and during the COVID-19 pandemic. Complementing hypotheses of worsened thrombotic and respiratory outcomes, we did not identify any changes in ICU length of stay, adjusted hospital mortality, or 30-day rehospitalization across study periods.
Recognizing that there may be risks to specific patient populations, we examined multiple subgroups and found no worsening of outcomes. While speculative, reduced post-transfusion thrombotic events during the post-vaccine period may reflect heightened awareness of the risk of venous thromboembolism during the COVID-19 pandemic. Our study also examined outcomes during the period of SARS-CoV-2 Omicron variant predominance, during which large numbers of vaccinated blood donors were infected with SARS-CoV-2 and may have had substantial boosting of antibody levels. Again, we found no worsening of outcomes in the study-eligible transfused population during this period nor among a subgroup of unvaccinated transfusion recipients; the latter notable because some recipients of blood products have expressed concern about the passive transfer of SARS-CoV-2 antigens or antibodies.19 Our findings are also consistent with clinical trial and observational data supporting the safety of CCP and laboratory-based studies that did not find evidence of an impact of CCP transfusion on the adaptive immune response of recipients.38
We focused on evaluating outcomes among transfusion recipients during study periods with known variation in donor SARS-CoV-2 infection and vaccination.10–12 However, it is worth recognizing that other factors occurring during the COVID-19 pandemic did not appear to impact outcomes in our cohort. Several studies found increased mortality for non-COVID illnesses during the COVID-19 pandemic.39–41 Widespread disruption of care delivery of healthcare services, including elective surgeries and procedures as well as preventative services, such as cancer screening, was recognized. Periods of national blood shortages also occurred during the COVID-19 pandemic.42,43 Despite these factors, we found no worsening in outcomes among a group of transfused patients within an integrated healthcare delivery system.
Some limitations should be emphasized. While our patient population reflects the regional community practice of transfused adults at 21 medical centers in Northern California, it may not reflect pediatric age groups, or specific populations (e.g., immunocompromised and obstetric patients). We attempted to control for other factors that might be related to patient survival (e.g., admission severity of illness, comorbidity indices and concomitant RBC transfusions); however, residual confounding may persist.
We chose length of stay as a sensitive but non-specific outcome that might encompass morbidity effects related to a blood donor characteristic. While length of stay provides little insight into biologic mechanisms, a lack of association, in parallel with thrombotic and pulmonary outcomes, is nonetheless reassuring. Lastly, we were unable to examine direct relationships between blood donor antibody titers and outcomes in transfusion recipients and thus may not be able to detect rare adverse effects. Additional analysis will link transfusion of these plasma-containing blood products with donor SARS-CoV-2 spike and nucleocapsid antibody results and survey data on donor infection and vaccination.44 These planned linked donor-transfusion recipient analyses will also help answer blood safety questions regarding criteria for the timing of blood donation after SARS-CoV-2 infection or vaccination.
In conclusion, we found no associations between periods of differing blood donor SARS-CoV-2 infection and vaccination and multiple clinical outcomes in SARS-CoV-2 negative transfusion recipients of plasma and platelet components. We found no association between pre-COVID, pre-vaccine, and post-vaccine study periods and unadjusted or adjusted rates of thromboses or increased oxygen requirements, ICU length of stay, adjusted hospital mortality, or rehospitalization. Our findings are reassuring for both clinicians and professionals involved in blood banking and do not indicate any changes are necessary to current transfusion practice.
Acknowledgements
The NHLBI Recipient Epidemiology Donor Evaluation Study-IV (REDS-IV-P), domestic component, is the responsibility of the following persons:
Hubs:
A.E. Mast and J.L. Gottschall, Versiti Incorporated, Milwaukee, WI
B. Custer and E. Vickinsky, University of California, San Francisco, San Francisco, CA
J. Hendrickson and B. Spencer, Yale University School of Medicine, New Haven, CT
Data coordinating center:
Central laboratory:
P.J. Norris and M. Stone, Vitalant Research Institute, San Francisco, CA
Publication committee chairman:
P. Ness, Johns Hopkins University, Baltimore, MD
Steering committee chairs:
S. Kleinman, University of British Columbia, Victoria, BC, Canada
C.D. Josephson, Johns Hopkins All Children’s Hospital, St. Petersburg, Florida and Johns Hopkins School of Medicine, Baltimore, MD
National Heart, Lung, and Blood Institute, National Institutes of Health:
B. Hailu, S. Zou, and K. Malkin
Financial Support:
This work was supported by research support from the National Heart, Lung, and Blood Institute as well as by funding support from the National Institute of Allergies and Infectious Diseases (NHLBI Contracts HHSN 75N92019D00032 and HHSN 75N92019D00033)
Appendix Figure 1:
Nationwide SARS-CoV-2 Mortality and Vaccination Estimates
Data presented with permission from the Centers for Disease Control https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/about-vaccine-data.html; https://data.cdc.gov/Case-Surveillance/COVID-19-Case-Surveillance-Public-Use-Data-with-Ge/n8mc-b4w4). The blue line shows the total number of reported deaths nationally due to COVID-19 during each study period. The red line shows the proportion of the population who received SARS-CoV-2 vaccination.
Appendix Table 1:
Number and proportion transfused blood components
| Transfused blood component | Pre-COVID (n=10,310) | Pre-Vaccine (n=4,580) | Post-Vaccine (n=6,860) |
|---|---|---|---|
| Red blood cell | 59% | 61% | 63% |
| Number of units per hospitalization | 3 (2–5) | 3 (2–5) | 3 (2–5) |
| Total number of transfused units | 26,468 | 12,654 | 20,508 |
| Platelet | 62% | 64% | 70% |
| Number of units per hospitalization | 2 (1–3) | 2 (1–3) | 2 (1–3) |
| Total number of transfused units | 20,686 | 9,955 | 16,644 |
| Plasma | 55% | 53% | 49% |
| Number of units per hospitalization | 2 (1–3) | 2 (1–3) | 2 (1–4) |
| Total number of transfused units | 17,684 | 8,194 | 11,385 |
Appendix Table 2:
Trends in increased oxygen requirements in subgroups of plasma or platelet recipients
| Patient characteristics | Component Type | Pre-COVID (n=8,096) | Pre-Vaccine (n=3,572) | Post-Vaccine (n=5,381) | p-valuea |
|---|---|---|---|---|---|
| Male | 510/4,523 (11.3) | 214/2,032 (10.5) | 352/3,013 (11.7) | 0.45 | |
| Plasma | 133 (8.0) | 49 (7.5) | 71 (8.7) | 0.74 | |
| Platelets | 196 (8.8) | 79 (7.4) | 142 (8.4) | 0.38 | |
| Plasma & Platelets | 181 (27.9) | 86 (27.3) | 139 (28.1) | 0.97 | |
| Female | 327/3,573 (9.2) | 123/1,540 (8.0) | 225/2,368 (9.5) | 0.25 | |
| Plasma | 106 (7.1) | 44 (7.2) | 56 (7.3) | 0.98 | |
| Platelets | 101 (6.3) | 33(4.7) | 67 (5.5) | 0.25 | |
| Plasma & Platelets | 120 (25.1) | 46 (21.4) | 102 (27.4) | 0.27 | |
| Age 18–59 | 240/2,147 (11.2) | 97/1,061 (9.1) | 188/1,629 (11.5) | 0.12 | |
| Plasma | 63 (8.9) | 27 (8.1) | 36 (8.0) | 0.84 | |
| Platelets | 76 (7.3) | 24 (4.6) | 50 (6.0) | 0.11 | |
| Plasma & Platelets | 101 (25.4) | 46 (22.3) | 102 (29.5) | 0.16 | |
| Age 60–75 | 350/3,096 (11.3) | 140/1,327 (10.5) | 254/2,052 (12.4) | 0.24 | |
| Plasma | 89 (8.7) | 33 (8.0) | 52 (9.9) | 0.58 | |
| Platelets | 131 (8.3) | 55 (7.9) | 108 (9.1) | 0.60 | |
| Plasma & Platelets | 130 (26.6) | 52 (24.0) | 94 (27.5) | 0.65 | |
| Age 76+ | 247/2,853 (8.7) | 100/1,184 (8.5) | 135/1,700 (7.9) | 0.70 | |
| Plasma | 87 (6.1) | 33 (6.4) | 39 (6.4) | 0.97 | |
| Platelets | 90 (7.6) | 33 (5.9) | 51 (5.6) | 0.16 | |
| Plasma & Platelets | 70 (29.1) | 34 (31.8) | 45 (25.3) | 0.47 | |
| Elective Admission | 232/1,517 (15.3) | 95/672 (14.1) | 190/1,147 (16.6) | 0.37 | |
| Plasma | 21 (7.5) | 7 (5.3) | 16 (8.7) | 0.53 | |
| Platelets | 103 (11.8) | 45 (11.2) | 95 (13.3) | 0.51 | |
| Plasma & Platelets | 108 (29.5) | 43 (31.2) | 79 (31.6) | 0.84 | |
| Emergency Admission | 605/6,579 (9.2) | 242/2,900 (8.3) | 387/4,234 (9.1) | 0.38 | |
| Plasma | 218 (7.6) | 86 (7.6) | 111 (7.9) | 0.93 | |
| Platelets | 194 (6.6) | 67 (4.9) | 114 (5.2) | 0.03 | |
| Plasma & Platelets | 193 (25.3) | 89 (22.7) | 162 (26.3) | 0.43 | |
| Surgical Admission | 456/2,884 (15.8) | 184/1,193 (15.4) | 337/1,925 (17.5) | 0.20 | |
| Plasma | 113 (9.7) | 36 (8.4) | 64 (10.3) | 0.58 | |
| Platelets | 144 (13.1) | 61 (12.0) | 125 (14.8) | 0.32 | |
| Plasma & Platelets | 199 (32.3) | 87 (34.1) | 148 (32.3) | 0.85 | |
| Medical Admission | 381/5,212 (7.3) | 153/2,379 (6.4) | 240/3,456 (6.9) | 0.37 | |
| Plasma | 126 (6.3) | 57 (6.8) | 63 (6.5) | 0.90 | |
| Platelets | 153 (5.6) | 51 (4.0) | 84 (4.0) | 0.01 | |
| Plasma & Platelets | 102 (20.0) | 45 (16.4) | 93 (22.8) | 0.12 | |
| SARS-CoV-2 Unvaccinated | 837/8,096 (10.3) | 335/3,568 (9.4) | 129/1,287 (10.0) | 0.29 | |
| Plasma | 239 (7.6) | 92 (7.3) | 22 (6.0) | 0.52 | |
| Platelets | 297 (7.8) | 111 (6.3) | 36 (5.3) | 0.02 | |
| Plasma & Platelets | 301 (26.7) | 132 (24.9) | 71 (30.2) | 0.31 |
P-value for trends across study period
Appendix Table 3:
Trends in thrombosis in subgroups of plasma or platelet recipients
| Patient Characteristic | Component Type | Pre-COVID (n=7,468) | Pre-Vaccine (n=3,362) | Post-Vaccine (n=5,029) | p-valuea |
|---|---|---|---|---|---|
| Male | 218/4,288 (5.1) | 95 (4.9) | 112 (3.9) | 0.05 | |
| Plasma | 61 (4.3) | 21 (3.6) | 25 (3.3) | 0.49 | |
| Platelets | 84 (3.9) | 42 (4.1) | 45 (2.8) | 0.11 | |
| Plasma & Platelets | 73 (9.9) | 32 (9.3) | 42 (7.7) | 0.38 | |
| Female | 142/3,180 (4.5) | 53/1,416 (3.7) | 77/2,136 (3.6) | 0.24 | |
| Plasma | 41 (3.4) | 18 (3.5) | 18 (2.8) | 0.78 | |
| Platelets | 61 (4.2) | 24 (3.6) | 40 (3.6) | 0.66 | |
| Plasma & Platelets | 40 (8.0) | 11 (4.8) | 19 (5.0) | 0.12 | |
| Age 18–59 | 115/2,068 (5.6) | 54/1,063 (5.1) | 57/1,596 (3.6) | 0.02 | |
| Plasma | 26 (4.1) | 15 (4.6) | 13 (3.1) | 0.54 | |
| Platelets | 44 (4.5) | 20 (4.1) | 23 (3.0) | 0.28 | |
| Plasma & Platelets | 45 (9.9) | 19 (7.6) | 21 (5.1) | 0.03 | |
| Age 60–75 | 140/2,786 (5.0) | 46/1,208 (3.8) | 89/1,847 (4.8) | 0.24 | |
| Plasma | 33 (4.1) | 10 (3.0) | 18 (4.1) | 0.63 | |
| Platelets | 63 (4.3) | 26 (4.0) | 41 (3.8) | 0.83 | |
| Plasma & Platelets | 44 (8.6) | 10 (4.6) | 30 (9.0) | 0.13 | |
| Age 76+ | 105/2,614 (4.0) | 48/1,091 (4.4) | 43/1,586 (2.7) | 0.04 | |
| Plasma | 43 (3.6) | 14 (3.3) | 12 (2.3) | 0.38 | |
| Platelets | 38 (3.3) | 20 (3.6) | 21 (2.4) | 0.32 | |
| Plasma & Platelets | 24 (8.8) | 14 (12.7) | 10 (5.5) | 0.09 | |
| Elective Admission | 89/1,498 (5.9) | 24/664 (3.6) | 48/1,096 (4.4) | 0.04 | |
| Plasma | 12 (5.6) | 4 (3.6) | 10 (5.8) | 0.69 | |
| Platelets | 41 (4.5) | 14 (3.3) | 14 (2.0) | 0.03 | |
| Plasma & Platelets | 36 (9.9) | 6 (4.5) | 24 (10.6) | 0.12 | |
| Emergency Admission | 271/5,970 (4.5) | 124/2,698 (4.6) | 141/3,933 (3.6) | 0.04 | |
| Plasma | 90 (3.7) | 35 (3.6) | 33 (2.7) | 0.29 | |
| Platelets | 104 (3.9) | 52 (4.1) | 71 (3.5) | 0.66 | |
| Plasma & Platelets | 77 (8.8) | 37 (8.4) | 37 (5.3) | 0.02 | |
| Surgical Admission | 194/2,758 (7.0) | 70/1,178 (5.9) | 96/1,886 (5.1) | 0.02 | |
| Plasma | 60 (6.3) | 17 (4.6) | 24 (4.5) | 0.25 | |
| Platelets | 53 (4.8) | 5 (4.8) | 27 (3.1) | 0.16 | |
| Plasma & Platelets | 81 (11.8) | 28 (9.9) | 45 (9.2) | 0.31 | |
| Medical Admission | 166/4,710 (3.5) | 78/2,184 (3.6) | 93/3,143 (3.0) | 0.37 | |
| Plasma | 42 (2.5) | 22 (3.0) | 19 (2.3) | 0.61 | |
| Platelets | 92 (3.7) | 41 (3.5) | 58 (3.1) | 0.57 | |
| Plasma & Platelets | 32 (5.8) | 15 (5.2) | 16 (3.7) | 0.32 | |
| SARS-CoV-2 Unvaccinated | 360/7,468 (4.8) | 148/3,358 (4.4) | 52/1,268 (4.1) | 0.41 | |
| Plasma | 102 (3.9) | 39 (3.6) | 13 (3.6) | 0.89 | |
| Platelets | 145 (4.0) | 66 (3.9) | 24 (3.7) | 0.94 | |
| Plasma & Platelets | 113 (9.1) | 43 (7.5) | 15 (5.6) | 0.13 |
P-value for trends across study period
Appendix Table 4:
Trends in thrombosis and oxygen requirements in hospitalizations by study period
| Study period | Pre-COVID | Pre-Vaccine | Post-Vaccine | ||
|---|---|---|---|---|---|
| Pre-Omicron | Omicron | P-valuea | |||
| Increased oxygen requirement (n=17,049) | |||||
| Plasma only N=6,012 | 7.6% (239/3,156) | 7.4% (93/1,265) | 7.7% (74/966) | 8.5% (53/625) | 0.85 |
| Platelets only N=8,513 | 7.8% (297/3,812) | 6.3% (112/1,777) | 6.8% (114/1,675) | 7.6% (95/1,249) | 0.19 |
| Plasma and Platelets N=2,524 | 26.7% (301/1,128) | 24.9% (132/530) | 29.1% (149/512) | 26.0% (92/354) | 0.48 |
| Arterial or venous thrombosis (n=15,859) | |||||
| Plasma only N=5,108 | 3.8% (102/2,629) | 3.6% (39/1,097) | 3.7% (31/837) | 2.2% (12/545) | 0.30 |
| Platelets only N=8,010 | 4.0% (145/3,599) | 3.9% (66/1,690) | 3.3% (50/1,539) | 3.0% (35/1,182) | 0.26 |
| Plasma and Platelets N=2,741 | 9.1% (113/1,240) | 7.5% (43/576) | 7.3% (39/531) | 5.6% (22/395) | 0.12 |
P-value for unadjusted trends across study period including subgroups of pre-Omicron and Omicron periods during the Post-Vaccine period
Footnotes
Conflict of Interest Disclosures: No author reports any relevant conflicts of interest.
Ethics Committee Approval: All participating sites received IRB approval prior to performing the study.
CITATIONS:
- 1.Libster R, Pérez Marc G, Wappner D, et al. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. N Engl J Med. Feb 18 2021;384(7):610–618. doi: 10.1056/NEJMoa2033700 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Korley FK, Durkalski-Mauldin V, Yeatts SD, et al. Early Convalescent Plasma for High-Risk Outpatients with Covid-19. N Engl J Med. Nov 18 2021;385(21):1951–1960. doi: 10.1056/NEJMoa2103784 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet. May 29 2021;397(10289):2049–2059. doi: 10.1016/s0140-6736(21)00897-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Estcourt LJ, Turgeon AF, McQuilten ZK, et al. Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial. Jama. Nov 2 2021;326(17):1690–1702. doi: 10.1001/jama.2021.18178 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Bégin P, Callum J, Jamula E, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med. Nov 2021;27(11):2012–2024. doi: 10.1038/s41591-021-01488-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. Oct 23 2020;370(6515)doi: 10.1126/science.abd4585 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Vazquez SE, Bastard P, Kelly K, et al. Neutralizing Autoantibodies to Type I Interferons in COVID-19 Convalescent Donor Plasma. J Clin Immunol. Aug 2021;41(6):1169–1171. doi: 10.1007/s10875-021-01060-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Estcourt LJ, Cohn CS, Pagano MB, et al. Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma. Ann Intern Med. Sep 2022;175(9):1310–1321. doi: 10.7326/m22-1079 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Joyner MJ, Carter RE, Senefeld JW, et al. Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19. N Engl J Med. Mar 18 2021;384(11):1015–1027. doi: 10.1056/NEJMoa2031893 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Jones JM, Stone M, Sulaeman H, et al. Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021. Jama. Oct 12 2021;326(14):1400–1409. doi: 10.1001/jama.2021.15161 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Busch MP, Stramer SL, Stone M, et al. Population-Weighted Seroprevalence From Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, Vaccination, and Hybrid Immunity Among US Blood Donations From January to December 2021. Clin Infect Dis. Oct 3 2022;75(Suppl 2):S254–s263. doi: 10.1093/cid/ciac470 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Jones JM, Opsomer JD, Stone M, et al. Updated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Estimates Based on Blood Donations, July 2020-December 2021. Jama. Jul 19 2022;328(3):298–301. doi: 10.1001/jama.2022.9745 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Jones JM, Manrique IM, Stone MS, et al. Estimates of SARS-CoV-2 Seroprevalence and Incidence of Primary SARS-CoV-2 Infections Among Blood Donors, by COVID-19 Vaccination Status - United States, April 2021-September 2022. MMWR Morb Mortal Wkly Rep. Jun 2 2023;72(22):601–605. doi: 10.15585/mmwr.mm7222a3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Erikstrup C, Laksafoss AD, Gladov J, et al. Seroprevalence and infection fatality rate of the SARS-CoV-2 Omicron variant in Denmark: A nationwide serosurveillance study. Lancet Reg Health Eur. Oct 2022;21:100479. doi: 10.1016/j.lanepe.2022.100479 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Vickers MA, Sariol A, Leon J, et al. Exponential increase in neutralizing and spike specific antibodies following vaccination of COVID-19 convalescent plasma donors. Transfusion. Jul 2021;61(7):2099–2106. doi: 10.1111/trf.16401 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Spiliopoulou P, Janse van Rensburg HJ, Avery L, et al. Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy. Cell Death & Disease. 2023/01/20 2023;14(1):49. doi: 10.1038/s41419-022-05548-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Nissen-Meyer LSH, Czapp E, Naper C, Jensen T, Boulland LML. Screening for antibodies to HLA class I in apheresis donors following Covid-19 or SARS-CoV-2 vaccination. Transfus Apher Sci. Oct 2022;61(5):103567. doi: 10.1016/j.transci.2022.103567 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Ramirez GA, Gautam-Goyal P, Shariatmadar S, et al. Passive transfer of SARS-CoV-2 antibodies with platelet transfusions. Transfusion. Apr 2022;62(4):764–769. doi: 10.1111/trf.16841 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Jacobs JW, Bibb LA, Savani BN, Booth GS. Refusing blood transfusions from COVID-19-vaccinated donors: are we repeating history? Br J Haematol. Feb 2022;196(3):585–588. doi: 10.1111/bjh.17842 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Jacobs JW, Binns TC, Chooljian DM, et al. Blood bans and COVID-19: Government attempts to influence medicine and science threaten us all. Am J Clin Pathol. Jul 6 2023;doi: 10.1093/ajcp/aqad071 [DOI] [PubMed] [Google Scholar]
- 21.Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med. Jul 2020;26(7):1017–1032. doi: 10.1038/s41591-020-0968-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Roubinian N TACO and TRALI: biology, risk factors, and prevention strategies. Hematology Am Soc Hematol Educ Program. Nov 30 2018;2018(1):585–594. doi: 10.1182/asheducation-2018.1.585 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Carson JL, Stanworth SJ, Dennis JA, et al. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. Dec 21 2021;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Karafin MS, Bruhn R, Westlake M, et al. Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database. Transfusion. Dec 2017;57(12):2903–2913. doi: 10.1111/trf.14370 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Morley SL, Hudson CL, Llewelyn CA, et al. Transfusion in adults: 10-year survival of red cell, plasma and platelet recipients following transfusion. Transfus Med. Aug 2016;26(4):264–70. doi: 10.1111/tme.12307 [DOI] [PubMed] [Google Scholar]
- 26.Goel R, Plimier C, Lee C, et al. Blood donor, component, and recipient-specific factors associated with venous thromboembolism in transfused hospitalized adult patients: Data from the recipient epidemiology and donor evaluation Study-III (REDS-III). Transfusion. May 2023;63(5):925–932. doi: 10.1111/trf.17292 [DOI] [PubMed] [Google Scholar]
- 27.Baumann Kreuziger L, Edgren G, Hauser RG, et al. Red blood cell transfusion does not increase risk of venous or arterial thrombosis during hospitalization. Am J Hematol. Feb 1 2021;96(2):218–225. doi: 10.1002/ajh.26038 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Escobar GJ, Gardner MN, Greene JD, Draper D, Kipnis P. Risk-adjusting hospital mortality using a comprehensive electronic record in an integrated health care delivery system. Med Care. May 2013;51(5):446–53. doi: 10.1097/MLR.0b013e3182881c8e [DOI] [PubMed] [Google Scholar]
- 29.Escobar GJ, Greene JD, Scheirer P, Gardner MN, Draper D, Kipnis P. Risk-adjusting hospital inpatient mortality using automated inpatient, outpatient, and laboratory databases. Med Care. Mar 2008;46(3):232–9. doi: 10.1097/MLR.0b013e3181589bb6 [DOI] [PubMed] [Google Scholar]
- 30.Kipnis P, Liu V, Escobar GJ. Accuracy of hospital standardized mortality rates: effects of model calibration. Med Care. Apr 2014;52(4):378–84. doi: 10.1097/MLR.0000000000000111 [DOI] [PubMed] [Google Scholar]
- 31.Toy P, Gajic O, Bacchetti P, et al. Transfusion-related acute lung injury: incidence and risk factors. Blood. Feb 16 2012;119(7):1757–67. doi: 10.1182/blood-2011-08-370932 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Chang SE, Feng A, Meng W, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun. Sep 14 2021;12(1):5417. doi: 10.1038/s41467-021-25509-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Zuo Y, Estes SK, Ali RA, et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med. Nov 18 2020;12(570)doi: 10.1126/scitranslmed.abd3876 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Abers MS, Rosen LB, Delmonte OM, et al. Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19. Immunol Cell Biol. Oct 2021;99(9):917–921. doi: 10.1111/imcb.12495 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Muri J, Cecchinato V, Cavalli A, et al. Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course. Nat Immunol. Apr 2023;24(4):604–611. doi: 10.1038/s41590-023-01445-w [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Jaycox JR, Lucas C, Yildirim I, et al. SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity. Nat Commun. Mar 9 2023;14(1):1299. doi: 10.1038/s41467-023-36686-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Carroll TD, Wong T, Morris MK, et al. Administration of vaccine-boosted COVID-19 convalescent plasma to SARS-CoV-2 infected hamsters decreases virus replication in lungs and hastens resolution of the infection despite transiently enhancing disease and lung pathology. bioRxiv. Aug 23 2023;doi: 10.1101/2023.08.22.553458 [DOI] [Google Scholar]
- 38.McDyer JF, Azimpouran M, Durkalski-Mauldin VL, et al. COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response. JCI Insight. Apr 24 2023;8(8)doi: 10.1172/jci.insight.167890 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Lau VI, Dhanoa S, Cheema H, et al. Non-COVID outcomes associated with the coronavirus disease-2019 (COVID-19) pandemic effects study (COPES): A systematic review and meta-analysis. PLoS One. 2022;17(6):e0269871. doi: 10.1371/journal.pone.0269871 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Leafloor CW, Imsirovic H, Qureshi D, et al. Characteristics and Outcomes of ICU Patients Without COVID-19 Infection-Pandemic Versus Nonpandemic Times: A Population-Based Cohort Study. Crit Care Explor. Apr 2023;5(4):e0888. doi: 10.1097/cce.0000000000000888 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.McLarty J, Litton E, Beane A, et al. Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study. Thorax. May 24 2023;doi: 10.1136/thorax-2022-219592 [DOI] [PubMed] [Google Scholar]
- 42.Al-Riyami AZ, Burnouf T, Wood EM, et al. International Society of Blood Transfusion survey of experiences of blood banks and transfusion services during the COVID-19 pandemic. Vox Sang. Jun 2022;117(6):822–830. doi: 10.1111/vox.13256 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Jacobs JW, Karafin MS, Allen ES, et al. Blood conservation strategies at United States hospitals during the COVID-19 pandemic: Findings from a multi-institutional analysis - International Society of Blood Transfusion survey. Transfusion. Nov 2022;62(11):2271–2281. doi: 10.1111/trf.17116 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Bouhou S, Lahjouji K, Masrar A. Blood donor eligibility after COVID-19 vaccination: the current state of recommendations. Pan Afr Med J. 2021;40:207. doi: 10.11604/pamj.2021.40.207.29119 [DOI] [PMC free article] [PubMed] [Google Scholar]