Long COVID (LC) affects an estimated 5-10% of individuals with SARS-CoV-2 causing a persistent physical, cognitive, and functional impairment with potentially severe socioeconomic consequences. While RECOVER-Adult cycle 1 established the largest, most comprehensive U.S. adult LC cohort (14,730 participants), key questions remain about long-term disease trajectories, biological mechanisms, and late-emerging complications. RECOVER-Adult cycle 2 will follow selected participants for two years each, focusing on neurocognitive, cardiopulmonary and infection-associated chronic conditions (IACC) such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and autonomic dysfunction. Using a case-cohort design, the study will investigate disease persistence versus resolution, biological mechanisms, and onset of new chronic illnesses, generating critical insights to guide prevention, treatment, and public health policy.

Inclusion Criteria:

• RECOVER-Adult 2024 LCRI 11 or greater, as defined by Geng et al, 2024;1 or
• At least 1 RECOVER-Adult LCRI symptom and either a) poor quality of life (QoL) as defined by a response of "poor" on the PROMIS-10 QoL question or b) "bother scale" is "quite a bit" or "very much" for corresponding LCRI symptom; or
• At least 1 National Academies of Sciences, Engineering, and Medicine (NASEM) common symptom and either a) poor QoL, or b) "bother scale" is "quite a bit" or "very much" for corresponding NASEM symptom.

Exclusion Criteria:

• Individuals who have a known or documented hemoglobin lower than 8.5 g/dL,
• Individuals who have not yet reached the age of majority,
• Individuals who are unable to provide consent,
• Individuals who are unwilling to consent to biospecimen collection or are unwilling to participate in the complete protocol, including all assessments and the cycle 2 visit schedule. Note that there are no exclusions related to blood volume collection. For healthy adults, the volume of blood collected (70.9 mL per visit and per year) is substantially lower than the federal minimal risk limit of 550 mL within 8 weeks,
• Individuals in hospice care,
• Individuals with a serious medical condition which would prevent in-person participation,
• Individuals participating in the study NIH RECOVER-Pediatric: Understanding the long-term impact of COVID on children and families, unless enrolled only as caregiver, or
• Long-term incarcerated individuals

Subset of adults previously enrolled in RECOVER-Adult cycle 1, who did not withdraw consent to use their data, and are located proximate to a cycle 2 enrolling site.

Data will be stored in registries housed by NHLBI BioData Catalyst® (BDC). Data will be available in three forms: 1) identified line-level, in a private data repository (RECOVER Data Gateway; RDG) maintained by BDC and accessible only to RECOVER Consortium investigators upon approval by a RECOVER PI and the RECOVER publications committee following established policies and procedures; 2) fully deidentified line-level, in a data repository at BDC accessible upon request to the public, for which access is managed by the Database of Genotypes and Phenotypes (dbGaP); and 3) publicly available, grouped, anonymized data for exploration and cohort-building through BDC using the Patient-centered Information Commons: Standardized Unification of Research Elements (BDC-PICSURE) tool. No permissions are required to access PIC-SURE because it is fully anonymized count data.

Immediately following publication. No end date.

Data will be stored in registries housed by NHLBI BioData Catalyst® (BDC). Data will be available in three forms: 1) identified line-level, in a private data repository (RECOVER Data Gateway; RDG) maintained by BDC and accessible only to RECOVER Consortium investigators upon approval by a RECOVER PI and the RECOVER publications committee following established policies and procedures; 2) fully deidentified line-level, in a data repository at BDC accessible upon request to the public, for which access is managed by the Database of Genotypes and Phenotypes (dbGaP); and 3) publicly available, grouped, anonymized data for exploration and cohort-building through BDC using the Patient-centered Information Commons: Standardized Unification of Research Elements (BDC-PICSURE) tool. No permissions are required to access PIC-SURE because it is fully anonymized count data.