REDS IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE)

Non-BioLINCC Resource: This resource is managed by the Study group. For information on obtaining biospecimens and their associated data, follow the Study Website link below.

Study Type
Epidemiology Study

Collection Type
Non-BioLINCC Resource

Study Period
1/1/2020 – 3/30/2022

NHLBI Division

Clinical Trial URLs

Primary Publication URLs

Parent Study Contact
Mars Stone, PhD,


Commercial Use Specimen Restrictions No

Non-Genetic Use Specimen Restrictions Based On Area Of Use No

Genetic Use Of Specimens Allowed? Yes, For Some Specimens

Genetic Use Area Of Research Restrictions Yes

Specific Consent Restrictions
Participants in the longitudinal follow-up study provided yes or no responses to consenting to three items: (1) blood/tissue sample being used for gene research in this study, (2) blood/tissue sample being stored/shared for future gene research, and (3) blood/tissue sample being stored/shared for future gene research for other health problems (such as cancer, heart disease, etc.).


This study focused on blood donors reporting post-donation information (PDI) consistent with COVID-19 by testing plasma from all available PDI donations for SARS-CoV-2 RNA by NAT. Subjects who were diagnosed with COVID-19 based on PDI reports or who tested positive by SARS-CoV-2 NAT on index donation plasma were enrolled into a longitudinal follow-up study which collected multiple samples for up to one-year post-infection. The longitudinal follow-up study also enrolled community members who reported a new positive SARS-CoV-2 NAT test in the prior 7-14 days. We sought to investigate PDI rates relevant to SARS-CoV-2 clinical disease and answer fundamental questions on the evolution of viremia, early immune responses, and waning of immunity over 3-12 months of follow-up.


Leveraging access to the blood supply and blood donors, the REDS-IV-P program began conducting the RESPONSE study in early 2020 in order to 1) evaluate if SARS-CoV-2 RNA was found in blood donations in the U.S. using an assay that could potentially be used to screen the blood supply if evidence of SARS-CoV-2 transfusion-transmission became apparent, 2) conduct serosurveys using optimized assays/algorithms to monitor antibody reactivity in blood donor populations over time, 3) enroll SARS-CoV-2 positive donors and others into a longitudinal cohort study to answer fundamental questions about the evolution of viremia and immune responses, and 4) establish a sharable biorepository that includes specimens collected early on in the infection and potentially large volumes of plasma from infected/convalescent donors.


Available specimens include approximately 3,800 index PDI plasma donations as well as plasma, serum, saliva, nasal swab, and buccal swab specimens from 102 longitudinal cohort members at approximately 1, 3, 6, 9, and 12 months after COVID-19 diagnosis and enrollment. Specimens from the subset of 40 longitudinal cohort members who were enrolled from the community are also available from 0, 7, and 14 days after COVID-19 diagnosis and enrollment.


During the COVID-19 pandemic, four blood collection organizations (the American Red Cross, Vitalant, the New York Blood Center, and Bloodworks Northwest) collected standardized information (enhanced PDI) on donors who reported PDI and met the study eligibility criteria. Plasma components from donations with relevant PDI were quarantined and sent to the testing laboratory for TMA and serological testing. The PDI study population included blood donors who self-reported a COVID-19 diagnosis or positive test result within 14 days of donation and those who reported at least 2 potential COVID-19 symptoms within 7 days of donation. To further probe the transfusion-transmission risk of RNAemic donors, a susceptible mouse model was established to test the same plasma units. In addition, to evaluate the risk associated with i.v. exposure to a known infectious product, lab-cultured SARS-CoV-2 variant B.1.1.7 (Alpha variant) was chosen as this strain was dominant in the United States at the time the RNA-positive donor samples were collected.

SARS-CoV-2-infected participants for the longitudinal follow-up study were identified from two populations: 1) Vitalant, American Red Cross, and New York Blood Center blood donors in the PDI study and 2) SARS-CoV-2-infected participants identified in the Denver and San Francisco areas within 14 days of a positive diagnostic test. Index plasma samples were derived from blood donations and the first visit from community participants; follow-up samples collected at subsequent study visits included blood, saliva, nasal swabs, and buccal swabs. As compared to blood donors, community participants had additional early samples collected at 1 week and 2 weeks. Nasal swab, saliva, and plasma samples were tested for RNA by TMA. RNA persistence in nasopharyngeal compartments was estimated by survival analysis using the Turnbull estimator for interval-censored data. The time interval from last positive result to the first negative result for each participant was used to estimate the median duration and 95% confidence interval for any positive test. Binding antibodies were assayed in plasma samples using anti-spike (S) and anti-nucleocapsid (NC) Ig total assays as well as anti-S IgG quantitative assay. Buccal swabs were tested for anti-S, anti-NC, and anti-RBD IgA.


No infectious virus was detected in plasma from RNAemic PDI 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.

Prior infection and vaccination both protected PDI donors from developing SARS-CoV-2 RNAemia and from symptomatic infection. RNAemia rates did not differ in the Delta and Omicron variant eras.

The longitudinal follow-up study of blood donors and community participants demonstrated that higher BMI was associated with both persistence of mucosal SARS-CoV-2 RNA and COVID-19 symptoms, underlining the need to focus prevention and treatment efforts on this swath of the population. Additionally, the correlation of low serum anti-S antibody responses with risk of reinfection provides a basis to inform vaccination strategies, particularly for persons at higher risk of serious outcome with COVID-19.


Resources Available

Specimens Only

Materials Available

  • Gingival Swab
  • Nasal Swabs
  • Peripheral Blood Mononuclear Cells
  • Plasma
  • Serum

Study Documents

  • There is no Data Dictionary associated with this study.

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