Gut Microbial Signatures in Long COVID: Potential Biomarkers and Therapeutic Targets

Abstract

Introduction: Following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, symptoms can persist for more than 12 weeks in over 10% of patients in a condition known as long coronavirus disease (COVID). Gut microbiota dysbiosis is correlated with long COVID, but the specific relationship between long COVID and the gut microbiome remains unclear. Here, we aimed to investigate connections between the gut microbiota and long COVID severity. Methods: Fecal samples were collected from 31 patients with long COVID, 14 with COVID-19 but not long COVID, and 23 healthy controls. The mean interval between COVID-19 diagnosis and sample collection was 65.5 (range: 13.0–110.3) weeks for patients with long COVID and 74.8 (range: 50.7–110.4) weeks for positive control group. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Patient-reported outcomes were used to comprehensively assess long COVID symptom severity. Results: Symptom severity was higher in patients with severe initial infections and significantly correlated with serum triglyceride, fasting blood glucose, and high-density lipoprotein-cholesterol levels. Results showed distinct microbial profiles in patients with long COVID. Leuconostoc, Actinomyces, and Granulicatella were significantly enriched, and they accurately distinguished patients with long COVID from controls, indicating their potential as long COVID biomarkers. Particular gut bacteria were significantly correlated with certain systemic, gastrointestinal, otolaryngologic, and visual symptoms. Parabacteroides, Eubacterium ventriosum group, and Rothia abundance was correlated with blood biomarkers that influence long COVID development, including total and low-density lipoprotein cholesterol and basophil levels. Conclusions: The gut microbial signature of patients with long COVID differed from that of healthy controls. Certain microbial genera showed significant differences between patients with long COVID and controls, suggesting potential as preliminary biomarkers and therapeutic targets for long COVID pending validation in larger studies.