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VEGFA sex-specific signature is associated to long COVID symptom persistence

Year: 2025

Type: article

Abstract: BACKGROUND: Long COVID involves persistent symptoms after COVID-19 recovery, affecting multiple organ systems for months or years. Risk factors include female sex, prior chronic conditions, severe SARS-CoV-2 infection, reinfections, and lack of vaccination. As a major public health concern, ongoing research continues to investigate its causes, mechanisms, and long-term effects. METHODS: Proteomic expression analysis of 171 individuals, in two time points, with confirmed SARS-CoV-2 infection, including 133 long COVID patients from the deeply characterized COVICAT cohort, assessed 1395 protein biomarkers using Olink® technology. Statistical analyses with linear mixed models examined protein expression changes, long COVID status, and sex-specific differences. Functional analysis included gene set enrichment analysis and protein-protein interaction networks. RESULTS: ). Network analysis identified 109 nodes and 274 edges, with VEGFA ranking highest in centrality. Dysregulated chemokine signaling, complement activation, and viral reactivation were also confirmed, consistent with prior studies. CONCLUSIONS: Using high-throughput proteomic profiling in a population-based cohort, we observed that vascular dysfunction, particularly involving VEGFA, is a key feature of long COVID, especially in milder cases, with significant overexpression of VEGFA in postmenopausal women. Sex-specific proteomic patterns suggest distinct recovery mechanisms, highlighting the need to consider sex, vascular health, and disease severity in the pathogenesis and management of long COVID.

Source: BMC Medicine

DOI: 10.1186/s12916-025-04402-6