NIH RECOVER: A Multi-Site Observational Study of Post-Acute Sequelae of SARS-CoV-2 Infection in Adults

The NIH Researching COVID to Enhance Recovery (RECOVER) initiative comprises a set of three combined retrospective and prospective, longitudinal, observational meta-cohort studies with nested case-control studies designed to define and characterize the epidemiology, natural history, clinical spectrum, and underlying mechanisms of post-acute effects of SARS-CoV-2 infection (PASC or Post-COVID syndrome) in a diverse study population representative of the general COVID-19 population in the US. Enrolled patients with and without known SARS-CoV-2 infection will be observed for clinical signs and symptoms of PASC and will be assessed for risk and resiliency factors and potential mediating factors associated with the severity and progression of PASC. The objective of the RECOVER initiative is to enhance knowledge of recovery from SARS-CoV-2 infections in order to support development of novel diagnostic and therapeutic interventions. Overarching scientific objectives are as follows: Characterize the incidence and prevalence of sequelae of SARS-CoV-2 infection. Characterize the spectrum of clinical symptoms, subclinical organ dysfunction, natural history, and distinct phenotypes identified as sequelae of SARS-CoV-2 infection.Define the biological mechanisms underlying pathogenesis of the sequelae of SARS-CoV-2 infection. The RECOVER observational studies comprise three cohorts across the lifespan (adult, pediatric, and tissue pathology (autopsy)). The data collection and data analysis plans for each cohort have been harmonized to use common data elements where feasible. Brief descriptions of each cohort are provided in the following paragraphs:1) NIH RECOVER: A Multi-site Observational Study of Post-Acute Sequelae of SARS-CoV-2 Infection in Adults (this study)The RECOVER adult cohort study is a combined retrospective and prospective, longitudinal, observational meta-cohort of individuals who will enter the cohort with and without SARS-CoV-2 infection and at varying stages before and after infection. Individuals with and without SARS-CoV-2 infection and with or without PASC symptoms will be followed to identify risk factors and occurrence of PASC. This study will be conducted in the United States and subjects will be recruited through inpatient, outpatient, and community-based settings. Study data including age, demographics, social determinants of health, medical history, vaccination history, details of acute SARS-CoV-2 infection, overall health and physical function, and PASC symptom screen will be reported by subjects or collected from the electronic health record using a case report form at specified intervals. Biologic specimens will be collected at specified intervals, with some tests performed in local clinical laboratories and others performed by centralized research centers or banked in the Biospecimen Repository. Advanced clinical examinations and radiologic examinations will be performed at local study sites with cross-site standardization. A summary of information available by request in the RECOVER Adult Cohort (this study) can be reviewed via the "Adult Cohort Dataset Release Notes" and the "REDCap Codebook for the Adult Cohort" documents.2) The RECOVER Post Acute Sequelae of SARS-CoV-2 (PASC) Pediatric Cohort Study: A Multi-Center Observational Study (data not yet released)The RECOVER pediatric study is a combined retrospective and prospective, longitudinal, observational meta-cohort of individuals ages newborn-25 years who will enter the cohort with and without SARS-CoV-2 infection at varying stages before and after infection. Individuals with and without SARS-CoV-2 infection and with or without PASC symptoms will be followed to identify risk factors and occurrence of PASC. This study recruit participants inpatient, outpatient, and community-based settings in the United States. Study data including age, demographics, social determinants of health, medical history, vaccination history, details of acute SARS-CoV-2 infection, overall health and physical function, and PASC symptoms will be reported by participants or collected from the electronic health record using a case report form at specified intervals. Biologic specimens will be collected at specified intervals, with some tests performed in local clinical laboratories and others performed by centralized research centers or banked in the Biospecimen Repository. Advanced clinical and radiologic examinations will be performed at local study sites with cross-site standardization.3) NIH RECOVER: A Multi-site Pathology Study of Post-Acute Sequelae of SARS-CoV-2 Infection (data not yet released)The RECOVER tissue pathology study is a cross-sectional study designed to define and characterize the epidemiology, natural history, clinical spectrum, and underlying mechanisms of post-acute effects of SARS-CoV-2 infection in a diverse population representative of the general COVID-19 population in the US. The autopsy study will characterize the pathology of PASC in (i) non-hospitalized patients who die 30 days or later from symptom onset of COVID-19, and (ii) hospitalized patients who die 30 days or later after discharge from a hospitalization for COVID-19. The study will include decedents who had previously fully recovered from SARS-CoV-2 infection (i.e., >30 days from onset in non-hospitalized, or >30 days from discharge in hospitalized patients), and decedents who meet clinical criteria of PASC as defined by the recent World Health Organization publication (see Section 5.4 below). The autopsy study will also explore the pathology of acute SARS-CoV-2 infection in a smaller subset of patients who died 15-30 days from symptom onset. This protocol defines the common set of clinical data elements, autopsy procedures for tissue collection, core measures, pathology protocols, shared pathology tissues, data elements, and methodology. Each investigator site is expected to perform autopsies on the decedents to address the pathophysiology of the potential long-term effects of SARS-CoV-2 infection on human health. The Consortium analysis plan aims to address research questions by incorporating: 1) tissue obtained from autopsies performed at each Phase II participant's site; and 2) tissue available from other pathology investigators/autopsy sites within the Consortium. ]]>
Release NotesData Dictionary Codebook: i2b2 Pediatric Main CohortEntry criteria for the RECOVER observational cohort studies are harmonized when feasible. The pediatric study includes enrollment from extant cohorts previously enrolled in other NIH-funded studies. The tissue pathology study includes enrollment of decedents with remote history of SARS-CoV-2 infection. Adult Study Inclusion Criteria:Patients will be eligible for inclusion if they are at least 18 years of age and have reached the age of majority in their state of residence Infected individuals must have suspected, probable, or confirmed SARS-CoV-2 infection as defined by WHO criteria within 36 months of enrollment, or positive SARS-CoV-2 infection-specific antibody testing, to meet inclusion criteria Participants must be willing to generally comply with the overall protocol (e.g. cannot agree to participate only for survey collection) and must expect to be available for the duration of the study. Adults with Suspected SARS-CoV-2 InfectionAn adult qualifies as having suspected SARS-CoV-2 infection if meeting criteria a, b or c below: a. Patients who meet the following clinical criteria plus one of the epidemiological criteria: Clinical criteria: i. Acute onset of fever and cough OR acute onset of any three of more of the following signs or symptoms: fever, cough, general weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, anorexia/nausea/vomiting, diarrhea, altered mental status. Note: Signs separated with a slash (/) are counted as one sign, in which the slash means “OR” (i.e., participants may have anorexia and/or nausea and/or vomiting; any combination of these symptoms counts as one of three symptoms needed to meet clinical criteria). Epidemiological criteria: i. Residing or working in an area with a high risk of transmission of virus: closed residential settings, humanitarian settings such as camp and camp-like settings for displaced persons; anytime within the 14 days before symptom onset; or ii. Residing or travel to an area with community transmission* anytime within the 14 days before symptom onset; or iii. Working in any health care setting, including within health facilities and within households or within the community; anytime within the 14 days before symptom onset. Note: For purposes of this protocol, we define “community transmission” as any county with at least substantial community transmission according to the CDC definition (50 or more cases per 100,000 in the past 7 days). If the participant has traveled to or from another country, use the most granular data available to determine transmission in that area. Historical data about community transmission levels can be found in the MOP. b. A patient with severe acute respiratory illness: (acute respiratory infection with history of fever or measured fever of ≥38C°; and cough; with onset within the last 10 days; and requires hospitalization). c. A person with a positive SARS-CoV-2 Antigen-RDT who is asymptomatic or meets some but not all clinical or epidemiologic criteria. Note: A patient who meets criteria for suspected SARS-Cov-2 infection who had a negative test at the time does NOT qualify as an infected case. Adults with Probable SARS-CoV-2 Infection An adult qualifies as having probable SARS-CoV-2 infection if meeting any one of a-d below: A patient who meets clinical criteria for suspected SARS-CoV-2 AND is a contact of a probable or confirmed case or linked to a COVID-19 cluster; A suspect case with chest imaging showing findings suggestive of COVID-19 disease; A person with recent onset of anosmia (loss of smell) or ageusia (loss of taste) in the absence of any other identified cause; Death, not otherwise explained, in an adult with respiratory distress preceding death AND was a contact of a probable or confirmed case or linked to a COVID-19 cluster (Not applicable to the RECOVER adult protocol) Note: A patient who meets criteria for probable SARS-Cov-2 infection who had a negative test at the time does NOT qualify as an infected case. Adults with Confirmed SARS-CoV-2 Infection An adult qualifies as having confirmed SARS-CoV-2 infection if meeting any one of a-d below: Any person with a positive Nucleic Acid Amplification Test (NAAT) OR positive SARS-CoV-2 antibody test*; Any person with a positive SARS-CoV-2 Antigen-RDT (including home-administered rapid test) AND meeting either the probable case definition or suspect criteria A OR B; An asymptomatic person with a positive SARS-CoV-2 Antigen-RDT (including home-administered rapid test) who is a contact of a probable or confirmed case; Any person with a positive SARS-CoV-2 nucleocapsid protein antibody test OR a positive SARS-CoV-2 spike protein antibody test IF not vaccinated *This protocol modifies the WHO criterion a to add detectable SARS-CoV-2 antibody as a qualifying test Adults with no SARS-CoV-2 Infection: Does not meet WHO criteria for a suspected, probable, or confirmed case of SARS-CoV-2 infection, AND Has negative NAAT SARS-CoV-2 testing from a respiratory specimen performed at the time of enrollment/screening AND Has a negative SARS-CoV-2 nucleocapsid protein antibody and spike protein antibody test (spike only if not vaccinated) performed at the time of enrollment, AND Lives in the same communities or recruited from the same sources as those in the SARS-CoV-2 infected cohort Note: uninfected individuals may participate independent of their vaccination status Adult Study Exclusion Criteria: Individuals who have not yet reached the age of majority Unable to provide consent Individuals in hospice care Any serious medical condition which would prevent long-term participation Individuals participating as children in the study NIH RECOVER-Pediatric: Understanding the long-term impact of COVID on children and families; individuals participating as caregivers are eligible for inclusion in the adult protocol Incarcerated individuals For adult cohort sites only: individuals who were pregnant at the time of their COVID infection or qualifying negative test, and whose pregnancy is ongoing For adult cohort sites only: individuals who were pregnant at the time of their COVID infection or qualifying negative test, and whose pregnancy is completed and resulted in a live birth Individuals who were pregnant at the time of COVID or qualifying negative test and who did not have a live birth remain eligible for inclusion at adult cohort sites Individuals who were pregnant at the time of COVID or are currently pregnant, regardless of pregnancy outcome, remain eligible for inclusion at pregnancy cohort sites For pregnancy cohort sites only: pregnant participants with an estimated date of delivery on or after December 31, 2023. ]]>
Version 3: Additional survey and clinical data were added for existing individuals.]]>