Nasal Microbiota and Clinical Features in Acute Flu-Like Illness: COVID-19 Status and Long COVID Follow-Up
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. 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% versus 48%, p=0.002). Nasal microbiota analysis revealed lower alpha diversity in COVID-19-positive individuals versus other ILI (Wilcoxon: Chao2 p=0.03305; Shannon p=0.02578; Simpson p=0.1082) but no differences in beta diversity or taxonomic composition between groups, including LC versus 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.