Nasal microbiota and clinical features in acute flu-like illness: COVID-19 status and long COVID follow-up.

Abstract

OBJECTIVES: Long COVID (LC) is a challenging medical condition. Reliable diagnostic and targetable biomarkers of LC for a proper and early diagnosis and clinical care are an unmet medical need. We aimed to evaluate targetable biomarkers for LC management. DESIGN: Comparison of nasal microbiota and clinical features in 291 individuals with acute influenzae-like illness (ILI), comparing COVID-19-positive (n=193) and negative (n=98) groups, with further stratification by long COVID (LC) outcomes (persistent symptoms >3 months). RESULTS: Clinical characteristics were balanced across groups, with upper respiratory symptoms predominating. Individuals who developed LC exhibited more cardiorespiratory symptoms during acute infection (70% vs 48%, P=0.002). Nasal microbiota analysis revealed lower alpha diversity in COVID-19-positive individuals vs other ILI (Wilcoxon: Chao2 index P=0.03305; Shannon diversity index P=0.02578; Simpson diversity index P=0.1082) but no differences in beta diversity or taxonomic composition between groups, including LC vs recovered individuals. EBV/CMV infection/reactivation was not associated with LC. Sensitivity analyses confirmed robustness to methodological and temporal biases. CONCLUSIONS: Findings suggest acute nasal microbiota disruption in individuals with COVID-19, but no LC-specific microbial profile