S2146 Long COVID and Long-Term Adverse Effects Following Vaccination for SARS-CoV-2: A Link With Gut Dysbiosis?

Introduction: Mounting evidence suggests a potential link between gut microbiome alterations and persistent symptoms following SARS-CoV-2 infection and following vaccination. Given the critical importance of the microbiome in host immunity we sought to investigate whether there might a microbiome signature associated with the development of long COVID and in those who experience severe and persistent symptoms following vaccination against SARS-CoV-2. Methods: In this study fecal samples from 31 patients with long COVID post SARS-CoV-2 infection, 37 individuals experiencing long-term adverse effects post-SARS-CoV-2 vaccination, and 20 healthy controls were collected at ProgenaBiome laboratories. DNA was extracted, purified, and normalized prior to library preparation utilizing shotgun methodology. Libraries were sequenced on the NextSeq 550 system with High-Output Kits V.2.5 for 300 cycles. Data was processed through the OneCodex bioinformatics pipeline to ascertain microbiome composition and relative abundances of top genera and phyla. A 2-sample t-test was used to evaluate statistical significance. Results: Compared to healthy controls, both patient groups exhibited significantly reduced levels of Bifidobacterium (P< 0.001) and Faecalibacterium (P = 0.002), genera known for their anti-inflammatory and protective properties. Additionally, Alpha diversity indices (Shannon and Simpson) revealed no significant differences between groups (Shannon P > 0.06; Simpson P > 0.10). Conclusion: These findings suggest a specific gut dysbiosis may play a role in the pathophysiology of Long COVID and persistent vaccine-related symptoms. Further larger studies should explore these findings and whether microbiome-targeted interventions may provide therapeutic benefit in these populations.