The Gut Microbiome Of Covid-19 Recovered Patients Returns To Uninfected Status In A Minority-Dominated United States Cohort

ABSTRACT

Introduction: Intestinal Microbiota Influences Both Susceptibility And Severity Of Bacterial And Viral-Induced Pathogenicity, Including Respiratory Diseases. In This Study, We Investigated The Relationship Between Intestinal Microbiota And Sars-Cov-2-Mediated Pathogenicity In The United States, Majority African American Cohort. Hypothesis: Intestinal Microbiota Is Modulated By Sars-Cov-2 Infection And Is Related To Symptom Severity And Recovery From The Disease. Methods: We Conducted A Single-Institution Study, Prospectively Collecting Fecal Samples From 50 Sars-Cov-2 Infected Patients Within 3 Days Of Icu Admission And 9 Sars-Cov-2 Recovered Patients Upon Testing Negative For The Virus. Feces Of 34 Uninfected Subjects At The Hospital With Unrelated Respiratory Medical Conditions Were Used As Controls. Total Fecal Rna/Dna Was Extracted And Microbiota Composition Was Determined Using 16s Rrna Gene Sequencing Of The V1-V3 Region. The 16s Rdna Sequencing Reads Were Processed Using Dada2 To Generate Amplicon Sequence Variants (Asv). Rt-Pcr On Fecal Rna Using Two Sets Of Validated Primer/Probes Was Performed To Establish The Presence Or Absence Of Sars-Cov-2 Viral Rna. Results: The Fecal Microbial Composition Was Found To Be Significantly Different Between Sars-Cov-2 Patients And Controls (Permanova Fdr-P=0.004), Independent Of Treatments Such As Antibiotic Exposure. Peptoniphilus, Corynebacterium And Campylobacter Were Identified As The Three Most Significantly Enriched Genera In Covid Patients Compared To Controls. Actively Infected Patients Were Also Found To Have A Different Gut Microbiota Than Recovered Patients (Permanova Fdr-P=0.003), And The Most Enriched Genera In The Covid-19 Patients Was Campylobacter, With Agathobacter Being Enriched In The Recovered Patients. No Difference In Microbial Community Structure Between Recovered Patients And Uninfected Controls Was Observed (Permanova Fdr-P=0.93), With Phocea Being The Top Genus Associated With Patients Who Recovered From Covid-19. Furthermore, No Difference In Alpha Diversity Between The Three Groups Was Noticed. More Importantly, 24 Of The 50 Covid-19 Patients (48%) Tested Positive Via Rt-Qpcr For Fecal Sars-Cov-2 Rna. A Significant Difference In Gut Microbial Composition Between Sars-Cov-2 Positive And Negative Samples Was Observed, With Klebsiella And Agathobacter Being Enriched In The Positive Cohort And Phocea In The Negative Cohort. No Significant Associations Between Microbiome Composition And Disease Severity Or Proton Pump Inhibitor Treatment Were Found. Conclusion: The Intestinal Microbiota Is Sensitive To The Presence Of Sars-Cov-2, With Increased Relative Abundance Of Genera (Campylobacter, Klebsiella) Associated With Gi Disease. Further Studies Are Needed To Investigate The Functional Impact Of Deleterious Bacterial Genera In Sars-Cov-2 On Gi Health.