To identify subgroups with similar social determinants of health (SDOH) characteristics using latent class analysis (LCA) and examine their associations with physical and mental health, cognitive function and missed workdays at 3 and 6 months post-SARS-CoV-2 infection. We hypothesised that intersecting SDOH factors would differentially influence COVID-19-related health outcomes across subgroups.

Prospective cohort study from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), with longitudinal data collection and cross-sectional analyses at baseline, 3-month and 6-month follow-ups.

Multicentre registry across eight US academic medical centres (Chicago, Dallas, Houston, Los Angeles, New Haven, Philadelphia, San Francisco and Seattle).

Adults aged ≥18 years, fluent in English or Spanish, with self-reported acute COVID-19 symptoms and a confirmed positive SARS-CoV-2 test within 42 days before enrolment (9 December 2020 to 12 August 2022), and access to an internet-connected device. Exclusions included incarceration, inability to provide informed consent, lack of confirmed SARS-CoV-2 infection or no internet access. Of 3791 eligible participants with complete baseline data, 2897 (76.4%) completed the 3-month follow-up and 2666 (70.3%) completed the 6-month follow-up; most were aged 18–49 years (74–75%), female (66–67%), white (86.6–87.5%) and non-Hispanic (86.6–87.5%).

Prespecified primary outcomes were physical and mental health (Patient-Reported Outcomes Measurement Information System (PROMIS)-29 V.2.1 T-scores for depression, anxiety, fatigue, sleep disturbance, pain interference, physical function and social participation), cognitive function (PROMIS Cognitive Function Short Form 8 T-scores) and missed workdays due to illness (binary: >1 week vs ≤1 week, from a single-item survey). All measures were self-reported and collected at baseline, 3 months and 6 months; no changes from protocol.

LCA identified a 4-class model as optimal (lowest Bayesian Information Criterion (BIC) after evaluating 1–7 class models; significant demographic differences (² p

In this US prospective cohort, SDOH-based subgroups showed persistent disparities in health outcomes post-SARS-CoV-2 infection. Findings highlight the urgent need for intersectional approaches to address systemic inequities in post-COVID-19 recovery.

NCT04610515.