Publication date: Jul 30, 2025

Long-term sequelae of COVID-19 remain critical public health concerns, with limited therapeutic options available. We conducted two case-control studies among COVID-19 infected individuals in the UK Biobank to explore the association of sociodemographic factors, clinical biomarkers, and comorbidities with the risk of two key phenotypes: Long COVID (LC, defined by patient self-report symptoms) and post-acute complications of SARS-CoV-2 infection (PACS, defined by clinical diagnosis), separately. Our study included 8,668 participants in the LC cohort (32% classified as cases) and 108,407 in the PACS cohort (with 2% being cases). Findings showed that age and sex were associated with both LC and PACS but in opposite directions. Additionally, obesity, socioeconomic deprivation, elevated C-reactive protein, triglyceride, vitamin D, HbA1c, cystatin C, urate, and alanine aminotransferase, and decreased HDL cholesterol and IGF-1, as well as CKD and COPD, were associated with LC. Most of these factors were also significant for PACS, except for alanine aminotransferase and vitamin D. These findings have potential mechanistic implications for the distinction between LC and PACS and can guide clinical implementation of identifying high-risk groups for targeted vaccination or other public health mitigation strategies.

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