Research ArticleCOVID-19 Open Access | 10.1172/JCI159876

Paula Saá,1 Rebecca V. Fink,2 Sonia Bakkour,3,4 Jing Jin,3,4 Graham Simmons,3,4 Marcus O. Muench,3,4 Hina Dawar,3 Clara Di Germanio,3,4 Alvin J. Hui,3 David J. Wright,2 David E. Krysztof,1 Steven H. Kleinman,5 Angela Cheung,2 Theresa Nester,6 Debra A. Kessler,7 Rebecca L. Townsend,1 Bryan R. Spencer,1 Hany Kamel,8 Jacquelyn M. Vannoy,8 Honey Dave,3 Michael P. Busch,3,4 Susan L. Stramer,1 Mars Stone,3,4 Rachael P. Jackman,3,4 Philip J. Norris,3,4,9 and for the NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)10

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Saá, P. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Fink, R. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Bakkour, S. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Jin, J. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Simmons, G. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Muench, M. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Dawar, H. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Di Germanio, C. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Hui, A. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Wright, D. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Krysztof, D. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Kleinman, S. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Cheung, A. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Nester, T. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Kessler, D. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Townsend, R. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Spencer, B. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Kamel, H. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Vannoy, J. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Dave, H. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Busch, M. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Stramer, S. in: JCI | PubMed | Google Scholar

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Stone, M. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Jackman, R. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Find articles by Norris, P. in: JCI | PubMed | Google Scholar |

1Scientific Affairs, American Red Cross, Gaithersburg, Maryland, USA.

2Westat, Rockville, Maryland, USA.

3Vitalant Research Institute, San Francisco, California, USA.

4Department of Laboratory Medicine, UCSF, San Francisco, California, USA.

5University of British Columbia, Victoria, British Columbia, Canada.

6Bloodworks Northwest, Seattle, Washington, USA.

7New York Blood Center Enterprises, New York, New York, USA.

8Vitalant, Scottsdale, Arizona, USA.

9Department of Medicine, UCSF, San Francisco, California, USA.

10See Supplemental Acknowledgments for REDS-IV-P details.

Address correspondence to: Philip Norris, 270 Masonic Avenue, San Francisco, California 94118, USA. Phone: 415.923.5769; Email: pnorris@vitalant.org.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Authorship note: PS, RVF, SB, MS, RPJ, and PJN contributed equally to this work.

Published July 14, 2022 - More info

Published in Volume 132, Issue 17 on September 1, 2022
J Clin Invest. 2022;132(17):e159876. https://doi.org/10.1172/JCI159876.
© 2022 Saá et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Published July 14, 2022 - Version history
Received: March 2, 2022; Accepted: July 12, 2022 View PDF Abstract

Respiratory viruses such as influenza do not typically cause viremia; however, SARS-CoV-2 has been detected in the blood of COVID-19 patients with mild and severe symptoms. Detection of SARS-CoV-2 in blood raises questions about its role in pathogenesis as well as transfusion safety concerns. Blood donor reports of symptoms or a diagnosis of COVID-19 after donation (post-donation information, PDI) preceded or coincided with increased general population COVID-19 mortality. Plasma samples from 2,250 blood donors who reported possible COVID-19–related PDI were tested for the presence of SARS-CoV-2 RNA. Detection of RNAemia peaked at 9%–15% of PDI donors in late 2020 to early 2021 and fell to approximately 4% after implementation of widespread vaccination in the population. RNAemic donors were 1.2- to 1.4-fold more likely to report cough or shortness of breath and 1.8-fold more likely to report change in taste or smell compared with infected donors without detectable RNAemia. No infectious virus was detected in plasma from RNAemic donors; inoculation of permissive cell lines produced less than 0.7–7 plaque-forming units (PFU)/mL and in susceptible mice less than 100 PFU/mL in RNA-positive plasma based on limits of detection in these models. These findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection.

Graphical Abstract Introduction

Although routine blood donation screening has rendered the blood supply extraordinarily safe with regard to tested infectious agents such as HIV and hepatitis B and C, in recent decades multiple infectious disease outbreaks have posed potential risks to the blood supply (1). These agents often originate as zoonoses and have a demonstrated capacity to spread rapidly between animal and human populations, and include respiratory viruses such as H1N1 influenza, SARS, MERS, and most recently SARS-CoV-2 (2). The attributes for an infectious agent to be transfusion transmissible include its presence in blood during an asymptomatic phase in the donor, survival in blood during processing and storage, infection in the recipient, and to be identified as clinically relevant, causing apparent disease. To ensure an adequate blood supply during a pandemic, blood establishments must consider whether blood collected during an outbreak may contain the infectious agent given that transfusion recipients are more susceptible to severe disease and serious sequelae.

In addition to screening, donor selection and questioning are in place to remove donors with recognized risk factors and potentially reduce the threat of infectious agents for which no assay is available or testing routinely performed. Many blood centers have procedures for collection of post-donation information (PDI) and retrieval of nontransfused blood products from donors who develop clinical symptoms, are diagnosed with an infection, or who recall risk information shortly after donation. PDI likely prevents transfusion-transmissible infections (TTIs) by allowing for retrieval of potentially contaminated units. PDI reports and testing of plasma units manufactured from these donations allows tracking of seasonal patterns of respiratory infections, including fever and general influenza-like illness (3). In 2020, PDI reporting expanded to include COVID-19–related symptoms or confirmed infection and is being used to monitor seasonal changes in PDI reporting rates relative to SARS-CoV-2 outbreaks. While the risk of transfusion-transmitted SARS-CoV-2 is thought to be low, several studies have noted detectable viral RNA in blood. SARS-CoV-2 RNAemia in hospitalized patients with critical disease ranges from 15% to 90%, compared with that in outpatients with mild disease ranging from 2% to 13% (4). In presymptomatic blood donors who were diagnosed with or developed symptoms of COVID-19 within 15 days of donation, 1% prevalence of SARS-CoV-2 RNAemia has been reported (5). A few studies have attempted to determine whether RNA-positive blood samples harbor infectivity using cellular models, all with negative results (4–8). This suggests that for SARS-CoV-2 RNAemia may not indicate the presence of infectious virions, consistent with what is known of other coronaviruses (9). The sensitivity of these models, however, is limited (10), making it difficult to rule out risk of transfusion transmission, particularly in more vulnerable transfusion recipients.

In this study, we investigated SARS-CoV-2 RNA and antibody reactivity in plasma from over 2,000 donors reporting SARS-CoV-2–compatible symptoms or diagnosis within 2 weeks after donation through routine blood center operational procedures at blood collection organizations collecting approximately 50% of the US blood supply. Using highly sensitive cellular and animal models, we evaluated risk of infection via intravenous (i.v.) exposure and screened RNA-positive plasma with the highest viral load for infectious virions.

Results

Rate of PDI during pre– and post–COVID-19 periods. PDI reports from the fourth quarter of 2016 through the end of July 2021 from the American Red Cross (representing approximately 40% of the US blood supply) were plotted and cross-referenced with public health data on pneumonia-, influenza-, and COVID-19–related mortality for the same period. From 2016 to 2019, the weekly rate of PDI reports ranged from 0.06 to 0.94 per 1,000 donations. A marked seasonality of PDI cases was evident; peaks coincided with mortality surveillance relating to pneumonia and influenza in winter months (Figure 1). In 2020 there were 3 additional peaks in PDI reports occurring in March, July, and November