R3 Seminar Recap: Using RECOVER biosamples to advance your research

To watch or read about our first webinar in this 2-part series, which focused on using RECOVER datapoints in Long COVID research, check out our recap.

RECOVER collects biosamples over time for additional study

RECOVER’s observational studies—which includes groups of adults, children, and adolescents—collect biosamples from study participants at multiple time points. These samples are collected alongside other study activities like attending in-person visits and taking symptom surveys. 

Some study participants will continue to the next phase of the observational studies and provide samples each year up to 48 months (4 years) for children and adolescents and up to 72 months (6 years) for adults.

Adult study participants provide samples starting at 3 months from enrollment or baseline (initial) SARS-CoV-2 infection (the virus that causes COVID-19). Available samples from the adult observational study include nasal or nasopharyngeal (nose and back of throat) swabs, blood plasma, serum, DNA (deoxyribonucleic acid) from white blood cell collection and saliva (spit), urine, and stool. 

Pediatric study participants provide samples at enrollment or 8 weeks after enrollment, depending on when they previously had COVID, or if they get COVID within 30 days of enrollment. Available samples from children and adolescents in the study include blood sponge, blood plasma, serum, and DNA from saliva. 

RECOVER also includes 2 unique groups—an in-utero cohort and caregivers—as part of the pediatric study. Caregivers can choose to share baseline samples of blood and saliva. These samples are not required for pediatric participation in the study. The in-utero cohort includes children born to pregnant women in the adult observational study. Blood samples are collected starting at 24 months (or 2 years old).

Watch the webinar on YouTube, starting at minute 35, for the full presentation on available samples and collection time points.

Tissue pathology (autopsy) study collects unique biosamples from adults

RECOVER’s tissue pathology (autopsy) study offers research opportunities to understand Long COVID mechanisms through tissue collected within the body. Study teams at 9 sites across the United States collect these samples within 24 hours after death. Jim Stone, MD, PhD, Chair of the RECOVER Autopsy Coordinating Committee, described the types of samples available for study.

The tissue samples collected from study participants allow researchers to analyze large quantities of tissue from 52 sites in the body. Tissues that are harder to obtain through biopsy (a process to remove a piece of tissue from living people and study it), like tissues from the heart and the brain, are included in this study. Dr. Stone emphasizes that the tissue collected is high quality with RNA (ribonucleic acid) intact, which makes the samples suitable for use through systems biology or ‑omics approaches.

The autopsy study also makes premortem (before death) clinical data available, which are collected from electronic health records, faxed medical charts, or the participant’s family. These additional data include demographics, past medical history, and findings from autopsy reports. Also included in these data are COVID and Long COVID symptoms; COVID tests, treatments, and vaccinations; and SARS-CoV-2 reinfections.

Watch the webinar on YouTube, starting around minute 5, for Dr. Stone’s review of autopsy study samples.

Using NHLBI BioData Catalyst® to assess feasibility of a biosample study

Data from RECOVER’s 3 observational study cohorts—including types of biosamples—are available through NHLBI BioData Catalyst® (BDC). BDC is a secure cloud-based ecosystem with tools and resources to support research analysis and workflows. 

To understand whether a proposed study using biosamples is feasible (possible), anyone can use BDC Powered by PIC-SURE (BDC-PIC-SURE) to view types of samples and associated study variables, like demographics, symptoms, and the time period during which the sample was collected. BDC-PIC-SURE provides open access to anonymized and aggregated RECOVER data. No fees or data access requests are required.

For approved studies using RECOVER biosamples, researchers will use BDC Powered by Seven Bridges (BDC-Seven Bridges) to analyze bioassays (measurements of biosamples) conducted in their laboratories and connect to additional datapoints if needed. The platform provides researchers with high-quality tools for analysis without needing to maintain their own computer hardware. BDC gives new users $500 in cloud computing credits to start.

Watch the webinar on YouTube, starting at minute 46, for a demo of BDC, helpful tips on searching for biosamples in RECOVER datasets, and technical support resources.

RECOVER research opportunities and next steps

To use RECOVER biosamples in a study, researchers must submit a study proposal through one of the initiative’s research opportunities. Review the Research Opportunities and Data Access Flowchart (PDF, 1 page) and applicable RECOVER study protocols to understand the steps required to apply.

For study proposals that aim to use autopsy samples, Dr. Stone shared the following considerations for tissue sample requests:

• Be reasonable in the number of participants chosen for your study.
• Be as specific as possible as to what types of Long COVID patients you are most interested in studying.
• Request the minimum amount of tissue necessary to do the planned study.
• Justify the need for frozen tissue and unstained paraffin-embedded tissue section slides. 

After a study proposal is initially approved through the following opportunities, the RECOVER Biospecimens Access Committee reviews biosample requests to make sure they are reasonable and will not impact other ongoing studies. The considerations noted earlier will help the committee review and finally approve your request.

Opportunity 1: Apply for a funded RECOVER study

RECOVER awards funding through Research Opportunity Announcements (ROAs) or Notices of Special Interest. Currently, ROA OTA-21-015K is seeking applications for ancillary studies that investigate the biological mechanisms underlying persistent Long COVID symptoms. This opportunity is expected to remain open through April 2027, depending on the availability of funds.

Learn how to apply for ROA OTA-21-015K.

Opportunity 2: Request approval for an externally funded RECOVER ancillary study

Researchers can apply to conduct independent research projects through RECOVER’s ancillary studies program. Approved ancillary studies should address research questions that are not included in RECOVER study protocols. Please note that researchers must secure funding for their ancillary study outside of RECOVER.

Learn how to apply for a RECOVER ancillary study.

The research opportunities noted earlier are structured to respect and protect the privacy of RECOVER study participants, in alignment with the National Institutes of Health (NIH) Data Management and Sharing Policy.

To find recordings and transcripts from previous R3 Seminars, visit the R3 Seminar Series webpage or the RECOVER YouTube channel.