BACKGROUND: Long COVID is clinically heterogeneous, with evolving symptom trajectories that complicate classification. Prior clustering studies often rely on Electronic Health Records data, risking underreporting. We examined longitudinal, community-based symptom clusters and associated factors.
METHODS: We analyzed CHASING COVID Cohort participants with confirmed SARS-CoV-2 infection between December 2020 and December 2022, ≥ 12 months of follow-up, and long COVID (≥ 1 new symptom and concurrent activity limitation 3-12 months post-infection, both absent pre-infection). The infection in this window was the index infection; those with pre-index long COVID were excluded. Symptoms were self-reported pre-infection and at ~ 3, 6, 9, and 12 months. Missing data were handled via multiple imputation by chained equations (30 datasets). Longitudinal K-means clustering was performed within each imputed dataset, with hierarchical aggregation to derive final assignments. Logistic regression (age- and sex-adjusted) assessed associations of demographic, clinical, and social factors with cluster membership. Within the highest-burden cluster, hierarchical clustering identified symptom phenotypes.
RESULTS: Of 1,787 infected participants, 511 met criteria (22% ≥50 years; 55% female; 60% White non-Hispanic; 54% mental health disorder; 7.2% immunodeficiency; 21% ≥2 comorbidities). Three longitudinal clusters emerged: highest, moderate, and lowest burden. The highest-burden cluster showed persistent multisystem symptoms (median 6 symptoms at 6-9 months) with frequent fatigue, concentration difficulty, post-exertional malaise, myalgia, sleep disturbance, gastrointestinal symptoms, headache, irritability, and mobility limitations. The moderate cluster peaked at 3 symptoms, while the lowest remained at 1 symptom. Older age (aOR 2.68, 95% CI 1.59-4.53), female sex (2.36, 1.48-3.76), mental health disorder (2.65, 1.65-4.25), and immunodeficiency (4.23, 1.71-10.51) were associated with highest vs. lowest burden. Within the highest-burden cluster, three phenotypes emerged: multisystemic dysfunction, psychiatric/neurological dysfunction, and physical/respiratory dysfunction.
CONCLUSIONS: Distinct long COVID clusters and phenotypes underscore heterogeneity and support tailored management and risk stratification.
Long Covid