Viral INfections in the Young Lung- The VINYL Clinical Consortium (UG3/UH3 Clinical Trial Optional)

Viral INfections in the Young Lung- The VINYL Clinical Consortium (UG3/UH3 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). This funding opportunity supports research on viral infections in the lungs of young individuals. Texas Health Resources, with its focus on health and research, could potentially apply for this type of research grant.

Expired RFA-HL-26-006: Viral INfections in the Young Lung- The VINYL Clinical Consortium (UG3/UH3 Clinical Trial Optional) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Heart, Lung, and Blood Institute ( NHLBI ) Funding Opportunity Title Viral INfections in the Young Lung- The VINYL Clinical Consortium (UG3/UH3 Clinical Trial Optional) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Resource-Related Research Project (Cooperative Agreements) See Part 2, Section III.

3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose This Notice of Funding Opportunity (NOFO) seeks applications for a Clinical Coordinating Center (CCC) comprised of one Clinical Center (CC) within the CCC, four additional Clinical Centers (CCs) and one Biorepository, coming in as one application for a single, phased award with milestone-driven transition from the first year to the remaining six years of the award, for a total duration of seven years.

A companion NOFO ( RFA-HL-26-008 ) seeks applications for one Data and Analytics Coordinating Center (DACC). Both opportunities will be submitted as companion applications with the same submission date to establish a consortium to elucidate Viral Infections in the Young Lung (VINYL): the VINYL consortium.

The primary goal of the consortium is to build an observational cohort with common data and a biospecimen collection to perform deep phenotyping of 1500 children between 0–2 years, including those born preterm, who are hospitalized in the United States with viral lower respiratory tract infections (LRTI) who have one or more of the following diagnoses: bronchiolitis, pneumonia, and pediatric acute respiratory distress syndrome (PARDS).

The consortium-wide pool of participants enrolled early during hospitalization will be deep-phenotyped and will be retained as a longitudinal cohort until pre-school age for evaluation of early and delayed pulmonary outcomes. Follow-up visits at 6 months post-discharge and at age 4–5 years are required. Enrollment of a control population is required to answer the research question(s).

Leveraging populations from contemporaneous networks and ongoing studies that could serve as comparator controls are encouraged. The longitudinal follow-up may employ a novel ‘hybrid’ cohort model, using questionnaires and electronic health records, along with in-person visits.

The VINYL Consortium seeks to understand the heterogeneity of severity, underlying pathobiology, and long term pulmonary outcomes of viral LRTI in young children hospitalized for this condition.

Research questions may include elucidation of clinical phenotype, impact of therapies upon outcomes, clarification of the impact of early viral infections on the ontogeny of the host respiratory immune response, lung and airway structure and function; and the relationship of these to pulmonary outcomes at 4–5 years of age. This has implications on future lung and airways health, including but not limited to wheezing at preschool age.

Research to understand neurocognitive effects and impact on sleep in this population is strongly encouraged.

Additionally, 2-4 prospective interventional mechanistic studies (Basic Experimental Studies in Humans, BESH), employing one or more clinical centers, are required to be proposed within the CCC application to better understand the pathobiology of viral LRTI and the impact of interventions to treat this condition in the young, developing lung.

The Biorepository within the CCC will lead the effort in collection and storage of biosamples, creation of an inventory, and linking the inventory to the DACC database, to facilitate access of data and biosamples. Throughout the program’s funding period, data (including imaging data) and biospecimens will be made available as a publicly accessible resource to the broader research community as rapidly and as simply as possible.

This will be a function of the companion DACC. The CCC is anticipated to be led by a pediatric clinical researcher with experience in observational and mechanistic human studies.

The CCC and Clinical Centers (CCs) will have expertise in enrolling participants into clinical studies of young, hospitalized children, and expertise in pediatric critical care, pediatric hospital medicine, pediatric pulmonary medicine, or neonatology within a multidisciplinary team that includes but is not limited to immunology, infectious diseases, and epidemiology.

The VINYL consortium will be supported by a DACC, which may be funded for up to 7 years to match the CCC funding. Both applications will be submitted and reviewed together. Funding Opportunity Goal(s) The Division of Lung Diseases supports research and research training on the causes, diagnosis, prevention, and treatment of lung diseases and sleep disorders.

Research is funded through investigator-initiated and Institute-initiated grant programs and through contract programs in areas including asthma, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, cystic fibrosis, respiratory neurobiology, sleep and circadian biology, sleep-disordered breathing, critical care and acute lung injury, developmental biology and pediatric pulmonary diseases, immunologic and fibrotic pulmonary disease, rare lung disorders, pulmonary vascular disease, and pulmonary complications of AIDS and tuberculosis.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO). Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Part 2.

Full Text of Announcement Section I. Notice of Funding Opportunity Description Bronchiolitis, a condition unique to the young lung, is the leading cause of hospitalization for viral lower respiratory tract infections (LRTI) in 0–2-year-old children, including those born preterm.

There are critical knowledge gaps in defining the condition, predicting its severity, and understanding the reasons for hospitalization, including the immature host respiratory immune response to viral infection, heterogeneity in response to different viruses, current interventions, practice variation in diagnosis and management, and subsequent long-term impact on lung health.

To address these needs and begin to move toward precision-based therapies, the Viral Infections in the Young Lung (VINYL) Consortium will conduct a deep phenotyping study of 1500 0-2 year old participants hospitalized in the United States with viral LRTI – bronchiolitis, pneumonia and/or Pediatric Acute Respiratory Distress Syndrome (PARDS), collect data and biospecimens to build a multidimensional database of this cohort that will be followed longitudinally until the age of 4–5 years, and thus elucidate the pathobiology and impact of early hospitalization for viral LRTI on lung and airways health at pre-school age.

This will create the largest multidimensional and publicly accessible database to characterize this unique population and elucidate mechanisms and heterogeneity of host responses to Viral Infections in the Young Lung.

The purpose of the VINYL initiative is to establish a cooperative consortium funded for up to seven years under the UG3/UH3 phased award for a Clinical Coordinating Center (CCC) and a companion U24 award for a Data and Analytics Coordinating Center (DACC, RFA-HL-26-008 ).

This NOFO seeks applications to support the VINYL Consortium CCC as a single award comprised of one clinical center (CC) within it, four additional CCs, and one Biorepository (located at the same or an allied site).

Each CC should consist of one main site and 1-3 optional sub-sites, and plan on enrolling participants in a Consortium-wide longitudinal cohort study with deep phenotyping and characterization at enrollment during hospitalization. The application should include proposals for 2-4 single or multi-site scientific projects that are mechanistic and meet the criteria for Basic Experimental Studies in Humans (BESH).

These may utilize the data, imaging, and/or biospecimens collected Consortium-wide in the proposal, with the goal of elucidating pathobiology but with no impact on clinical outcome, within this primarily pragmatic, observational study. The CCC Principal Investigator (PI) will lead one of the CC sites. The Biorepository may be led by a co-investigator.

A Multiple PI (MPI)-led application may be proposed, with a clearly described leadership plan. It is anticipated that each CC will enroll 300 participants between 0–2 years of age for detailed phenotyping during hospitalization, to meet the total enrollment goal of 1500 participants over 3 years. The cohort will be maintained until the participants are 4–5 years of age.

Each CC (together with sub-sites, if any) needs to provide evidence of ability to enroll 100 subjects per center per year, with emphasis on geographic variation and unique participant pools. The award will be a UG3/UH3 phased transitional award.

The 1-year UG3 phase will support development of the common protocol and procedures, site activation, and meeting regulatory requirements ideally completed within the first 9 months, with a goal for enrollment of the first subject by the end of Year 1. The UH3 phase should consist of longitudinal studies, envisioned as visits at 6 months post-discharge from hospital for assessments, and subsequent maintenance of a ‘hybrid’ cohort.

Cohort maintenance should employ in-person visits, telehealth, mobile technology, tracking devices and electronic health records, or a combination, depending on the research questions, capabilities and resources. A final visit should occur at 4–5 years of age for a comprehensive examination for pulmonary health, addressing the specific research question(s) posed of the cohort in the common protocol and BESH studies proposed.

The CCC and the Biorepository will oversee data (including imaging data), biospecimen-related document development, and finalization of data shells with the DACC.

The Consortium-wide common protocol for deep phenotyping of these infants during their hospital admission would typically include, but is not limited to, clinical data, imaging (including novel techniques), and biosample collection to answer specific research questions relevant to pathobiology, clinical care decisions, clinical course in hospital, interventions, and immediate outcomes.

Babies and infants admitted to the hospital, whether the pediatric floor or the intensive care unit, including those born preterm, should be included if they meet the inclusion criteria specific to the research questions posed. The longitudinal cohort study protocol, with harmonization between CCs and their sub-sites (if any), will collect data and samples based upon feasibility and ability to answer the research question(s).

But, it is strongly encouraged that as many subjects as possible (and not less than 1200 subjects) from the initial cohort are studied up to age 4–5 years. Additionally, the CCC application will be required to propose 2-4 scientific projects that address hypothesis-driven scientific questions that involve basic experimental studies in humans (BESH).

These scientific questions may be focused on the hospital course and/or post-hospital period, on pathobiology (such as central airway collapse versus peripheral airways obstruction in the pathobiology of wheeze, role of diaphragmatic fatigue in the pathophysiology of exhaustion and respiratory distress leading to hospitalization, biomarkers of disease severity, impact of the immunophenotype on clinical course and mechanistic bases of interventions and/or outcomes of severe LRTI in 0-2 year old children), and their relationship to pulmonary status at pre-school age.

This Consortium will generate key information about the heterogeneity (including clinical, physiological, and biological heterogeneity) and underlying mechanisms of viral LRTI, particularly as they relate to impact on ontogeny of the developing respiratory immunophenotype, that is both virus agnostic and virus specific, and may include the impact of the microbiome (including the virome and/or the fungome) and super-infection.

The consortium will allow examination of cellular mechanisms and/or pathways using current and novel molecular methods such as single cell technology and RNA sequencing. A pragmatic observational study of these young children, when hospitalized will help to understand and clarify the different presentations, therapies, and clinical outcomes.

The longitudinal follow-up will assess trajectory of respiratory health and lung development with detailed pulmonary phenotyping at pre-school age. Neurocognitive and sleep health evaluation at that time is strongly encouraged. Throughout the program’s funding period, data (including imaging data) and biospecimens collected will be made available as a resource to the broader research community.

Data collection will employ forward-looking data sharing policies compatible with broad consent to enable future research studies by others, both within and outside the Consortium. The process for sharing data and biospecimens throughout the program’s funding period with the broader research community will be developed in the first 6 months, consistent with NHLBI policies for deposition into NHLBI BioData Catalyst and BioLINCC.

Data and biospecimens are expected to be shared as rapidly as possible, with processes that are simple and achievable. Wherever possible, the consortium will not hold data or biospecimens for its exclusive use or for the exclusive use of one of its components, and will endeavor to make samples (including information about how the samples were obtained and processed) and data available to the broader research community.

In accordance with data and biospecimen policies set up within the first 6 months of the program, data will be deposited into NHLBI’s repositories (anticipated to be BioData Catalyst) and made available for use by the research community annually and at the end of the program..

Biospecimens will be deposited into NHLBI's repository (anticipated to be BioLINCC) and made available for continued use by the research community at the end of the program. Submission of biospecimens for genetic testing and multiomics analysis to TOPMed when appropriate and acceptable, is strongly encouraged.

Scientific questions that the VINYL consortium could help address, by providing a publicly accessible database of these participants include, but are not limited to: Why do young children have such severe disease? Why are babies born preterm at higher risk? What are the immune underpinnings of severe LRTI in this age group?

What are the prognostic indicators of clinical outcome-phenotypes and endotypes? What clinical interventions are effective and in which subgroups? How can those that are at risk for long term lung disease be identified?

Some Examples of Research Interest Identification of underlying endotypes and sub-phenotypes in Viral LRTI in 0-2 year old children who are admitted to the hospital. Use of Artificial Intelligence (AI) algorithms in metrics and measures of severity and clinical decision-making.

Novel approaches to analyze data from the inpatient setting - cutting-edge analytical workflows (e.g., machine learning and AI approaches) to elucidate and unpack human factors that influence treatment choices while in hospital. Impact of immunization against RSV (vaccine or antibodies) on the immunophenotype and on susceptibility to other respiratory viruses.

Specific characteristics and the underlying pathobiology of premature babies who develop severe Viral LRTI. Pathophysiology of the different clinical presentations- diaphragmatic function and fatigue, central airway collapse, contributions of pulmonary hypertension, intracardiac shunts and parenchymal disease as examples.

Relevant clinical, radiological, immunological and genetic, molecular and immunologic ‘omics’ signatures that aid diagnosis, choice of and response to specific therapies, prediction of outcome, prognosis including long-term pulmonary morbidity, susceptibility to subsequent infection severity or asthma. Trajectories of recovery after viral LRTI in young children and factors influencing them.

Pulmonary and airways health outcomes viral LRTI. Impact of the microbiome, virome, or fungome and other microbial infection/colonization on presentation, outcomes and pulmonary and immune outcomes. It is anticipated that the VINYL Consortium will be funded as a single award to the CCC, which will make sub-awards to the CCs and the Biorepository.

The successful single application will thus be enabled to pose common research questions, harmonize protocols and coordinate data and sample collection. These components will work together in a cooperative and interactive manner to develop, and implement a Consortium-wide longitudinal cohort study with deep phenotyping and characterization at enrollment during hospitalization.

Plans to share data (including imaging data) with researchers both within and outside the VINYL Consortium are required in the application.

The Investigator leading the Biorepository will create and maintain a database and repository of biospecimens, appropriately processed for the different novel investigative platforms being employed to answer the research questions, assist the CCs in biospecimen collection as needed and be responsible for distribution of samples within and outside the consortium as needed.

The Biorepository will provide to the DACC an inventory of biospecimens that are, or will be made available as the study progresses, along with clinical and other phenotyping information to investigators available on the VINYL database. In addition, the CCC and the CCs may propose a minimum of two and a maximum of 4 mechanistic sub-studies that may utilize one or more CCs in the application.

The final Consortium-wide common longitudinal cohort protocols with rationale, methods, and procedures for biospecimen collection will be developed or adapted for approval by the Steering Committee during the first six months of the program using the protocols and methods for biospecimens collection proposed by the successful CCC application.

The application must demonstrate the feasibility of the CCs, and any sub-sites, of enrolling at least 100 participants per CC per year throughout the ideal enrollment period of three years, bringing the total number of participants to 1500 to meet the goals of the program.

The CCC and the 5 CCs will be responsible for collecting and transferring clinical and imaging data for the Consortium-wide common protocol to the Data and Analytics Coordinating Center (DACC) for management, collation and establishment of the live publicly accessible platform. An independent Chair of the Steering Committee will be appointed by the NHLBI without any other roles or responsibilities within the study.

Investigators must agree to use common guidelines and a manual of procedures developed by the Steering Committee that will also include NIH Program Staff as voting members and other Institute representatives at the NIH as needed as non-voting members, who will serve in an advisory capacity to the NHLBI Program Scientist.

Clinical Coordinating Center (CCC), Biorepository and Clinical Centers (CCs): The responsibilities of the CCC include overseeing the preparation of informed consent templates, recruitment brochures, and other Consortium-wide study-related participant materials; ensuring that all CCC and CC personnel are trained on necessary human subject procedures including the informed consent process, VINYL Consortium policies, applicable regulations, and Good Clinical Practice (GCP); routine tracking and reporting of adverse events and unanticipated problems to NHLBI, the DSMB, and other regulatory agencies as appropriate; and monitoring study execution at CCs to assure compliance with the common protocol, manual of procedures, VINYL Consortium policies, applicable regulations, and guidelines throughout the duration of the program.

The CCC will be expected to identify any study-related issues at the CCs as early as possible, develop corrective and preventative action plans in consultation with the NHLBI, and oversee the implementation of the corrective and preventative action plans.

Estimated protocol cost funds for the Consortium-wide protocol will be part of the CCC award and will be distributed by the CCC to the five CCs as sub-awards in accordance with the budget approved by the Steering Committee and NHLBI. As such, the CCC application will be expected to request a line item for protocol costs which will be restricted for this use only.

Only research-related costs above those incurred as part of usual clinical care are eligible to be covered by reimbursement via protocol costs from the Coordinating Center. Costs for reimbursement will be in the form of capitated payments to the sites on a per participant basis.

Biorepository Establishment and Management The Biorepository must demonstrate expertise in specimen collection, handling, shipping, processing and storage, and cataloging of the source and ontogeny of the samples.

The centralized Biorepository will have the necessary personnel, equipment, and protocols and procedures for transfer of biospecimens from the enrolling sites to the centralized Biorepository, to core facilities/laboratories as needed for analysis in a timely manner, to investigators approved to obtain biospecimens during the project period, and to the NHLBI repository at the end of the project period.

The CCC and Biorepository will also develop standardized protocols for the collection, preparation, processing, storage, and shipment of biospecimens (e.g., blood, urine, lung specimens) into and out of the Biorepository, provide training of CC personnel on the proper collection, preparation, processing, and storage of biospecimens as needed, and will maintain accurate inventories of what is available in the Biorepository.

The Biorepository may exist either within the CCC institution or as a subaward.

Expenses associated with the day-to-day operations of a centralized Biorepository include those associated with collection containers, procurement, storage, and shipping of biospecimens collected as part of the Consortium-wide protocol from the CC sites to the CCC; training site coordinators and other study personnel to obtain the data and biospecimens for the protocols in a uniform manner; and instituting quality control measures.

It is anticipated that the biospecimens collected may include, but are not limited to, blood, urine, and lung specimens (e.g., sputum, tracheal aspirate, bronchoalveolar lavage fluid). The Biorepository budget is expected to include sufficient resources to establish procedures that meet quality standards of the NHLBI Biorepository (BioLINCC).

Expenses are expected to include plans for facilitating data and biospecimen analyses on Consortium-wide protocol biospecimens, shipping containers and shipping costs for the CCs, costs for storage at the CCCC Biorepository during the project period, costs to facilitate sharing of biospecimens with approved investigators within and outside the Consortium during the project period, and costs for final shipping to the NHLBI Biorepository upon study completion.

It is anticipated that CCs will ship biospecimens collected as part of the Consortium-wide protocol to the CCC Biorepository at regular intervals throughout the project period to facilitate sharing of samples both within and outside the Consortium. NHLBI expects the costs for routine biospecimen quality assurance to be included and described.

The biospecimen collection plan will be finalized by the Steering Committee, but the CCC is expected to present a vision and budget for the biospecimen collection. A subcontract may be proposed for the bio repository.

The Clinical Centers (CCs) will enroll participants hospitalized in the U.S. in the Consortium-wide longitudinal cohort study, and may participate either individually or together with other CCs in the mechanistic studies proposed in the application that do not impact clinical outcome (BESH). Between 2- 4 such studies that are feasible and within budget will be submitted together in the single application.

Each CC will be expected to enroll 300 subjects over years 1, 2 and 3 of the awards, for a total of 1500 participants to be followed-up at 6 months post discharge and retained until 4-5 years of age. Investigators must agree to use common guidelines and a manual of procedures developed by the Steering Committee for all VINYL Consortium studies.

Funding for the CC-specific scientific project(s), including personnel, related infrastructure costs, analysis of data, imaging, and/or biospecimen costs must be budgeted for in the CCC application. The CCs will be responsible for distributing the funds to any sub-sites.

CCs, in coordination with the CCC and DACC, are expected to (1) ensure that all participating sites are trained on VINYL Consortium policies, applicable regulations, and GCP; (2) be responsible for ensuring that study execution at the CC and sub-sites (when applicable) is compliant with the VINYL Consortium protocols, manual of procedures, and applicable regulations and guidelines throughout the duration of the program; and (3) routinely track and report adverse events and unanticipated problems, monitor enrollment and data quality, and identify and address any study-related issues through development of corrective and preventative action plans in consultation with the CCC and NHLBI.

CCC and CCs must agree to use of the single Institutional Review Board (sIRB) selected by the CCC for all VINYL Consortium studies, consistent with NIH policies regarding multi-site studies involving human subjects. The local IRBs at the CC sites (including the CC within the CCC) are expected to establish processes for working with the sIRB so that Consortium operations are streamlined as much as possible.

NHLBI will be responsible for overall support, direction and oversight of the VINYL Consortium. The NHLBI Program Office and Office of Grants Management will oversee the overall direction and progress of the VINYL Consortium.

In addition to regular grant stewardship, the NHLBI Program Officer and Project Scientist (envisioned to be the same individual) will be involved substantially with the awardees as one voting member of the Steering Committee, consistent with the Cooperative Agreement mechanism. The NHLBI will appoint an independent DSMB, Steering Committee chair and an independent Advisory Board to the Institute and the VINYL investigators.

Representatives from other ICs may participate as needed as non-voting members of the Steering Committee and will provide input to the NHLBI representative, when indicated, on items presented to the Steering Committee for a vote.

A Steering Committee composed of the principal investigators of the CCC and co-investigator of the Biorepository (if applicable), the DACC, CC investigators, a Steering Committee chair appointed by NHLBI, and NHLBI and other IC representatives will form the core governing body of the VINYL Consortium. All major scientific decisions will be determined by majority vote of the Steering Committee.

The CCC, Biorepository co-investigator, each CC (independent of multiple PIs), the DACC, and the NHLBI will have one vote each; the Steering Committee chair will have a vote in case of a tie vote among the other Steering Committee members. It is anticipated that the Steering Committee will meet once a month by conference call and by in-person meeting once a year (with virtual meetings as an option/alternative if necessary).

The Steering Committee has primary responsibility for the general organization of the VINYL Consortium, approval of the Consortium-wide longitudinal cohort study protocol and budget, including protocol revisions, before review by the DSMB, the conduct and monitoring of VINYL Consortium studies, the expeditious reporting of study results, and the rapid sharing agreements for VINYL consortium data and biospecimens.

Subcommittees of the Steering Committee will be established to oversee specific functions such as protocol development and oversight, ancillary studies, publications, biorepository, and data and biospecimen sharing.

The Steering Committee will monitor disclosures of financial interests and potential conflicts of interest among investigators, but such monitoring will not preclude investigators’ responsibility to report their financial disclosures to their respective recipient institutions. Recipient members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

During the first 6-9 months of the U24 award to the DACC, which matches the UG3 award year (Year 1 of the companion award to the CCC), the Steering Committee (in conjunction with the CCC and with assistance from the DACC) will be responsible for developing the consortium-wide longitudinal cohort protocol that outlines standardized procedures for enrolling participants and procedures and methods for the collection of data, images, and biospecimens across all participating sites within the VINYL Consortium.

It is expected that the Consortium-wide protocol may be refined iteratively over the course of the project period as new data become available. The protocol, and any subsequent changes to that protocol, in the observational component, the peer-reviewed mechanistic studies (BESH) and the longitudinal and follow-up evaluation will be voted on and must be approved by majority vote of the Steering Committee to be implemented.

In addition, NHLBI will appoint an independent expert advisory board to the VINYL consortium, the VINYL Advisory Board (VAB) that may be consulted for opinions and advice.

The Advisory Board will comprise a chairperson, clinicians, and scientists with expertise in infectious diseases, viral immunology, airways disease, pediatric hospital and critical medicine and pulmonology, observational study design, outcome measures, biostatistics, ethics, biospecimen collection, and other areas of expertise as needed.

The Advisory Board will evaluate scientific merit, experimental design and approach, feasibility, appropriateness in the context of the VINYL Consortium program goals, and consistency with NHLBI’s mission and policies. VINYL Advisory Board (VAB) An independent VINYL Advisory Board (VAB) will be appointed by and be advisory to the NHLBI.

It will consist of a chairperson, clinicians, and scientists who are recognized as experts in viral infections in the young lung, immunology, infectious diseases, cell biology, molecular biology, observational study design, outcome measures, biostatistics, ethics, biospecimen collection, and other areas of expertise as needed.

This Board may be consulted for independent advice on any aspect of the underlying science, the relevance and significance of research questions, clinical monitoring, human subject protection, policies and procedures, analysis of outcomes, and data analytics while building the VINYL consortium.

Observational Study and Data and Safety Monitoring Board An independent Observational Study and Data and Safety Monitoring Board (DSMB) will be appointed by and advisory to the NHLBI. The DSMB will be responsible for providing independent advice to the NHLBI regarding study safety and related ethical considerations, the progress of the study, and the appropriateness of continuing the studies performed by the VINYL Consortium.

The DSMB will oversee the observational studies in hospitalized participants, the BESH and the longitudinal cohort studies and concur with the implementation of the Consortium-wide protocol and associated studies. The DSMB will meet approximately every six months, with interim meetings being held as necessary.

Responsiveness to this NOFO NHLBI will accept applications that include Basic Experimental Studies in Humans (BESH) - mechanistic