The Science Behind Transfusion Safety in the COVID-19 Era

Introduction

The COVID-19 pandemic reshaped nearly every aspect of medicine-including the world of blood transfusion. Early fears and misinformation sparked concerns: Could SARS-CoV-2, the virus behind COVID-19, be transmitted through blood? Would blood from vaccinated donors cause unexpected side effects? As the pandemic evolved, so did the questions-and the need for clear, evidence-based answers.

On a recent episode of Blooducation Baristas, Dr. Nareg Roubininan, a pulmonary intensive care clinician, and Dr. Mike Bush, a pathologist and virologist, shared the results of their research (Blood donor SARS-CoV-2 infection or vaccination and adverse outcomes in plasma and platelet transfusion recipients and Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS-CoV-2 infection and vaccination). Their studies, conducted in collaboration with major blood centers and academic institutions, provide the most comprehensive data yet on transfusion safety during the COVID era. Here’s what every clinician, transfusion specialist, and patient should know.

The Early Days: Uncertainty and Urgency

In the first months of the pandemic, uncertainty reigned. Social media fueled fears that COVID-19 could be transmitted through blood products. These concerns were compounded by the rollout of COVID-19 vaccines, with some patients and advocacy groups expressing anxiety about receiving blood from vaccinated donors.

Dr. Bush, who began his career during the HIV/AIDS crisis, understood the gravity of these concerns. “We had to do the studies to really prove that,” he explained, referencing earlier experiences with transfusion-transmitted infections. Recently, their team launched large-scale investigations to address both the risk of viral transmission and the possible effects of donor vaccination on transfusion recipients.

Study Design: A Multi-Phase, Evidence-Based Approach

To answer these pressing questions, Drs. Roubinian and Bush designed a series of studies that examined:

• Transfusion from donors with recent COVID-19 infection

• Transfusion from donors who had received COVID-19 vaccines

• Potential effects of high antibody titers in donor blood

• Recipient outcomes, including respiratory and thrombotic events

Cohort and Data Collection

The studies focused on patients from Kaiser Permanente Northern California, a region with over four million residents. Nearly all plasma and platelet products for these hospitals were supplied by the American Red Cross and Vitalant, ensuring comprehensive data linkage between donors and recipients.

Donor Testing and Classification

Donors were classified based on:

• Serological testing: Spike and nucleocapsid antibody assays identified prior infection, vaccination, or both (“hybrid immunity”).

• Donor history questionnaires: Captured vaccination status, infection history, and timing of exposures.

This dual approach allowed researchers to accurately categorize donor status and correlate it with recipient outcomes.

Key Outcomes: What Was Studied?

The research zeroed in on three critical outcomes in transfusion recipients:

• Respiratory complications (e.g., pulmonary edema, increased ventilation needs)

• Thrombotic events (e.g., blood clots, a known risk in both COVID-19 and some vaccines)

• General outcomes (hospital length of stay, mortality, 30-day rehospitalization)

To avoid confounding, the studies excluded patients who were already experiencing severe illness prior to transfusion.

Findings: No Evidence of Increased Risk

COVID-19 Transmission via Blood

Despite early fears, the data revealed:

“No evidence supporting transfusion transmission of SARS-CoV-2.”-Dr. Mike Bush

Even in cases where donors developed COVID-19 shortly after donation, extensive follow-up and laboratory studies showed no cases of transfusion-transmitted infection.

Blood from Vaccinated Donors

A persistent concern was whether blood from vaccinated donors could cause adverse effects. The studies found:

• No increased risk of respiratory or thrombotic complications in recipients of plasma or platelet products from vaccinated donors.

• No dose-dependent relationship between the amount of antibody in donor blood and adverse outcomes.

• No evidence that recently vaccinated or recently infected donors posed additional risk.

High-Antibody and Hybrid Immunity

Even when transfused products had high levels of COVID-19 antibodies-either from recent infection, recent vaccination, or both-there was no association with worsened outcomes in recipients.

Convalescent Plasma

Randomized controlled trials of convalescent plasma (plasma from recovered COVID-19 patients) similarly showed no adverse effects, supporting the broader conclusion that antibody-rich plasma is safe for transfusion. (Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.)

Addressing Special Populations and Limitations

While the findings are robust and reassuring, the researchers acknowledged certain limitations:

• Primarily adult population: Most data came from adult patients; further research is needed for pediatric and neonatal populations, which tend to be more conservative in transfusion practices.

• Short-term outcomes: The studies focused on immediate and short-term outcomes post-transfusion. Long-term effects, while unlikely based on current evidence, require ongoing surveillance.

• Immunocompromised patients: Special consideration is needed for patients receiving intravenous immunoglobulin (IVIG), as these products now contain high levels of SARS-CoV-2 antibodies. However, no adverse effects have been observed to date.

The Broader Impact: Science, Communication, and Future Threats

The implications of this research extend beyond COVID-19:

• Empowering clinicians: The data provide a factual foundation for conversations with patients who are hesitant or fearful about transfusion risks.

• Guiding policy: Regulatory bodies and hospital transfusion services can update guidelines with confidence, knowing that the blood supply remains safe.

• Preparing for future threats: The methodologies developed-linking donor and recipient data, rapid serological testing, and outcome tracking-create a template for responding to future infectious threats, including emerging viruses and novel therapies.

As Dr. Bush noted:

“We’ve learned how to do this… and we’ll be prepared as emerging threats or concerns come up.”

Looking Ahead: The Platinum Era of Transfusion Medicine

The pandemic accelerated innovation in transfusion safety research. As gene and cell therapies become more common, similar studies will be crucial in assessing the safety of blood products from donors who receive novel treatments.

The blood supply’s safety record during COVID-19 is a testament to the power of rigorous science, collaboration, and transparent communication. For clinicians, patients, and the public, the message is clear: Transfusion medicine has risen to the challenge-and continues to keep the blood supply safe.

Take-Home Messages

• No evidence exists that blood from COVID-19-infected or vaccinated donors increases risk to transfusion recipients.

• Extensive studies, including serological testing and outcome tracking, support the safety of plasma and platelet transfusions in the COVID era.

• Ongoing surveillance and research are essential, especially for special populations and as new therapies emerge.

• Clinicians now have robust data to reassure patients and guide transfusion practices with confidence.

Final Thoughts

The COVID-19 pandemic tested the resilience of healthcare systems and the blood supply. Thanks to the dedication of researchers like Drs. Roubinian and Bush, the transfusion medicine community can move forward-armed with science, not speculation-into whatever challenges the future may bring.

For more in-depth discussion, listen to the full Blooducation Baristas episode here.

Additional Resources:

1.) ABC Blood Bulletin Directed Donations and COVID-19 mRNA Vaccinated Blood Donors https://bit.ly/blood_bulletin_directed_donations_pdf

2.) How physicians like me are grappling with requests for unvaccinated donor blood

3.) Jeremy W. Jacobs, Garrett S. Booth, Mithya Lewis-Newby, et al. Medical, Societal, and Ethical Considerations for Directed Blood Donation in 2025. Ann Intern Med. [Epub 13 May 2025]. doi:10.7326/ANNALS-25-00815