Oral microbiota in patients with long COVID: A pilot study.

INTRODUCTION: The COVID-19 pandemic continues to pose a substantial threat to global public health. While most efforts have focused on the acute phase SARS-CoV-2 infection, a significant proportion of individuals experience persistent symptoms after infection, known as "persistent COVID disease" (PCD). The etiology of PCD remains poorly understood, although some evidence suggests that microbiota, particularly those located in the upper respiratory tract, may play a role. The aim of this study was to investigate differences in the composition of the oral microbiota, salivary cytokine, and short-chain fatty acids (SCFAs) concentration, between PCD and healthy controls. METHODS: We conducted an age- and sex-matched case-control study. Oral bacterial communities were profiled by 16S rDNA gene (V3-V4) amplicon high-throughput sequencing. Salivary IL-6 and TNF-α concentrations were measured, and SCFA were quantified by liquid chromatography-tandem mass spectrometry. Cognitive and fatigue status were assessed with the Montreal Cognitive Assessment (MoCA) and the Modified Fatigue Impact Scale (MFIS). RESULTS: Oral-microbiota α/β-diversity did not differ between groups; salivary cytokines were likewise similar. After Benjamini-Hochberg correction, no SCFA differences were significant (q>0.05); valeric acid showed the strongest uncorrected signal (p=0.02; r=0.52) but not after adjustment (q=0.23; power ≈0.73). CPD participants had lower MoCA and higher MFIS scores than controls (both p<0.005). CONCLUSIONS: The increase of valeric acid levels in PCD patients warrants further investigation to clarify its potential biological role and implications in the pathophysiology of this syndrome.