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Journal Article Ppublish

PubMed: 40450635 DOI: 10.1007/s40121-025-01167-6

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

Infect Dis Ther 14(7):1461-1475

Authors: Soyoung Oh, Sujin An, Kihyun Park, Soohyung Lee, Yoo Min Han, Seong-Joon Koh, Joowon Lee, Hyerin Gim, Donghyun Kim, Haesook Seo

Affiliations

  • Infectious Disease Research Center, Citizen's Health Bureau, Seoul Metropolitan Government, Seoul, Republic of Korea.
  • Department of Food and Drug, Seoul Metropolitan Government Research Institute of Public Health and Environment, Seoul, Republic of Korea.
  • Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
  • Department of Family Medicine, Seoul Medical Center, Seoul, Republic of Korea.
  • Department of Internal Medicine and Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
  • Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea. Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea. Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea.
  • Infectious Disease Research Center, Citizen's Health Bureau, Seoul Metropolitan Government, Seoul, Republic of Korea. Department of Tuberculosis, Seoul Metropolitan Seobuk Hospital, Seoul, Republic of Korea.

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.

MeSH

Coronavirus, Genes, Genes, Rrna, Sars-Cov-2, Blood, Lipoproteins, Biomarkers, Signs And Symptoms, Cholesterol, Covid-19, Therapeutics, Gastrointestinal Microbiome, Microbiota, Infections, Post-Acute Covid-19 Syndrome