OTA-21-015C Link: https://covid19.nih.gov/sites/default/files/2021-07/PASC-MHP-ROA.pdf

With this ROA, NIH is soliciting applications for the Mobile Health Platform (MHP) component of the REsearching COVID to Enhance Recovery (RECOVER) Initiative. The MHP will facilitate research that relies on the collection, annotation, harmonization, curation, and sharing of digital health data collected via mobile health technology by the RECOVER Investigator Consortium to complement and augment existing clinical, electronic health record (EHR), and other real-world data in an integrated manner.

Background on the RECOVER Initiative

Recovery from SARS-CoV-2 infection is extremely variable with many recovering quickly, while for other patients there are important post-acute sequelae. Reported symptoms among persons who have been infected with SARS-CoV-2 range from mild to incapacitating, may persist after recovery from acute disease, may involve multiple organs and systems, and can adversely affect overall quality of life. In some cases, new symptoms and findings are reported that appear linked to the timing of acute infection but emerge subsequently and evolve over time. The magnitude of the public health impact of these sequelae is currently unknown but potentially large, given the numbers of individuals across the age spectrum who have been and will be infected with SARS-CoV-2. It is a public health priority that we better understand and develop strategies to prevent and treat post-acute sequalae of SARS-CoV-2 infection (PASC) and that these strategies enable rapid innovation, evolution, and adaptation as more is learned about PASC and its potential impact on public health. The goal of the trans-NIH RECOVER Initiative is to rapidly improve understanding of recovery after SARS-CoV-2 infection and to prevent and treat PASC. Toward these ends, the Initiative is designed to address these fundamental scientific questions:

• What is the clinical spectrum of and biology underlying recovery from acute SARS-CoV-2 infection over time?
• For those patients who do not fully recover, what is the incidence/prevalence, natural history, clinical spectrum, and underlying biology of this condition? Are there distinct phenotypes of patients who have prolonged symptoms or other sequelae?
• Does SARS-CoV-2 infection initiate or promote the pathogenesis of conditions or findings that evolve over time to cause organ dysfunction or increase the risk of developing other disorders?

The Initiative is designed to be a collaborative and inclusive approach for rapidly advancing our understanding of the recovery process and the epidemiology (including incidence/prevalence) and natural history (including duration) of PASC. Studies conducted will characterize: the clinical spectrum of recovery from SARS-CoV-2 infection, including the subset of patients who have symptoms of disease more than 4 weeks after infection with SARS-Cov-2; the individual, clinical, and contextual factors that contribute to the duration, types of symptoms, and severity of disease; phenotypes of patients who have prolonged symptoms or other sequelae; the impact of treatments for acute COVID-19 or for post-acute symptoms on the duration and severity of symptoms; and factors that impact the outcomes in patients infected by SARS-CoV-2.

At the heart of the Initiative is the rapid launch of the SARS-CoV-2 Recovery Cohort and SARSCoV-2 Recovery Cohort Investigator Consortium.

The SARS-CoV-2 Recovery Cohort is a collaborative meta-cohort that will leverage ongoing fitfor-purpose cohorts, as well as new cohort studies, to chart the process of recovery in diverse adult and pediatric populations. This will include patients acutely infected with SARS-CoV-2 (acute cohort), as well as persons suffering from post-acute symptoms (post-acute cohort), along with appropriate control participants. The RECOVER Initiative will emphasize inclusive participation and leverage a variety of clinical platforms, including large-scale EHR/health systems-based cohort studies; large and long-standing longitudinal studies; COVID-19 clinical trials/networks; and COVID-19 clinics, registries, and observational studies. These will be augmented by utilization of mobile and digital health strategies for participant recruitment, data collection, and follow-up.

SARS-CoV-2 Recovery Cohort studies will characterize PASC symptoms and findings and their trajectory over time and across the lifespan. They will include investigator-initiated studies taking a variety of approaches to probe for evidence of tissue injury or organ system dysfunction or other conditions (e.g., immunologic, pulmonary, cardiac, neurologic/cognitive, metabolic, mental health). Some may focus on special populations including children, the elderly, pregnant or lactating people, or those with relevant comorbidities. Diversity in study populations will be necessary to generalize findings to the U.S. population affected by SARSCoV-2 infection. Toward this end, RECOVER Initiative investigators are encouraged to collaborate where feasible with other relevant NIH initiatives (e.g., Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP), Community Engagement Alliance (CEAL) Against COVID-19 Disparities).

Given the heterogeneity of symptoms and findings involving multiple tissues and systems, understanding PASC will require a multidisciplinary approach. Toward this end, all study investigators under this initiative will work together in a SARS-CoV-2 Recovery Cohort Investigator Consortium with the goal of immediately launching a multi-disciplinary collaboration to conduct rapid systematic screening and follow-up evaluations of SARS-CoV-2 infected individuals, to provide a resource for in-depth multi-disciplinary phenotyping, and to pool data and share biospecimens and data across studies. After award, Consortium investigators will be convened to rapidly develop a streamlined set of common core protocol elements (specific hypotheses, design elements, screening evaluations, exams, lab tests, functional assessments, imaging, digital health measures, patient-reported outcomes, common data elements etc.) and to provide a collaborative for multi-disciplinary phenotyping. Consortium investigators may also propose site- or study-specific hypotheses that, due to specific expertise or technology constraints, may only be possible in subsets of the consortium as sub-studies or ancillary studies. Successful applicants will be required to participate in collaborative protocol development and implementation.

Importantly, the Initiative also will leverage EHR- and other Real-World Data-based approaches to provide data and information on the incidence/prevalence of post-acute sequelae, PASC symptoms, imaging, and lab test results to inform the definition of PASC; describe patient demographics; identify comorbidities; define health care utilization patterns; provide real world data for comparative effectiveness studies, as well as reducing time and scope of potential clinical trial design and implementation; and inform PASC clinical characterization through health systems-based patient common data elements (CDEs). (See https://www.fda.gov/science-research/science-and-research-special-topics/real-worldevidence for a description of real-world data.)

Exploratory clinical trials testing strategies to treat symptoms and prevent progression of SARSCoV-2 infection to PASC are also a critical part of this initiative.

Also, critically important to understanding the pathology associated with PASC will be Autopsy Cohort Studies that will include in-depth histopathologic analysis of multiple organs and tissues, including brain, to identify tissue injury due to SARS-CoV-2 infection and/or its sequelae that lead or contribute to PASC.

RECOVER Initiative Structure The research-related activities of the RECOVER Initiative will be supported by multiple components working closely together, including but not limited to:

• A Clinical Science Core to coordinate the investigator consortium; facilitate clinical protocol development, implementation, monitoring, and data analysis; foster the use of common data elements across groups; promote multi-disciplinary collaboration; and foster community engagement.
• A Data Resource Core to coordinate RECOVER data management, harmonization, integration, and sharing, and provide analytical tools and statistical support to the Clinical Science Core.
• A RECOVER Biorepository Core to receive, manage, and make available a diverse range of biospecimens derived from RECOVER Investigator Consortium studies.
• Data Repositories (e.g., Digital Health Data Repository, Clinical and Observational Data Repository) to deploy, manage and grow a robust, secure digital infrastructure.
• A Mobile Health Platform to develop customized mobile apps to collect PASC digital health measures in the Clinical Recovery Cohort studies.
• An Administrative Coordinating Center to provide central coordination and oversight.

This ROA requests proposals to implement and manage the Mobile Health Platform component of the RECOVER Initiative. The Mobile Health Platform will collaborate closely with the other components of the RECOVER Initiative to gather digital health data to augment the other data collected by the Recovery Cohort studies. The Clinical Science Core, Data Resource Core, and Biorepository Core are the subjects of a separate but related ROA: OTA-21-015A. The research studies (Clinical Recovery Cohort Studies, Autopsy Cohort Studies, and EHR- and Other RealWorld Data-based Studies) are also the subject of a separate but related ROA: OTA-21-015B. Applicants are strongly encouraged to review these related ROAs in detail and to be familiar with their contents. The Data Repositories will be the subject of a separate ROA.

Consortium investigators will be required to develop, implement, and participate in a collaborative governance structure that includes community representatives and affected persons. All study investigators are required to rapidly and appropriately share data, software, and biospecimens (timeline to be determined by the RECOVER Governance Committee) and to consent participants for general research use of data, other medical information, and biospecimens.

This initiative supports NIH’s longstanding commitment to making the results and outputs of NIH-funded research available to the public through effective and efficient FAIR data sharing practices. Consortium investigators will make research data and biospecimens available through the Clinical Science Core, Biorepository Core, and Data Resource Core at agreed upon milestones and upon completion of their study. Researchers will agree not to distribute controlled-access datasets and will acknowledge use of RECOVER datasets through citations in manuscripts and presentations.

For more information click Link: https://covid19.nih.gov/sites/default/files/2021-07/PASC-MHP-ROA.pdf