Dysbiosis & Long COVID
DETERMINING THE IMPACT OF MICROBIAL DYSBIOSIS ON IMMUNE AND BARRIER DYSFUNCTION IN LONG COVID
1 other identifier
observational
400
1 country
1
Brief Summary
The SARS-CoV-2 virus causes COVID-19, which ranges from mild initial symptoms to severe multi-organ dysfunction. While some patients recover to their baseline states, others develop a long COVID, or post-acute sequelae of SARS-CoV-2 (PASC) consisting of symptoms persisting \>2-6 months post-infection. PASC symptoms include post-exertional malaise, fatigue, and heart palpitations as well as incident GI disorders, cognitive dysfunction, and arthritis. Based on prevalence/incidence studies, it is estimated that more than 30 million people in the US have ever developed PASC with 10-11% of patients or 11 million people continuing to feel symptoms to the present day10. SARS-CoV-2 vaccines are only \~32% effective against infection at 4 months post-vaccination11, only 15% effective against the development of PASC12, and only 20% of American adults have received an updated booster as of December 202313. It is therefore imperative that the scientific community make progress in identifying underlying causes of PASC to develop effective treatments. This study will identify microbial metabolites associated with PASC-mediated gut dysbiosis and establish a tractable in vitro model to test T cell-gut epithelium dynamics to develop novel bio-therapeutics for multiple post-viral conditions. This case-control study will collect biospecimens (matched stool \& blood) samples from 400 people with and without long COVID (200 participants/group) to understand how COVID-induced dysbiosis impacts symptom severity, immune suppression, and gut barrier dysfunction both ex vivo and in vitro.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Jan 2025
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 21, 2025
CompletedFirst Submitted
Initial submission to the registry
February 11, 2025
CompletedFirst Posted
Study publicly available on registry
February 13, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2029
March 2, 2026
February 1, 2026
3.9 years
February 11, 2025
February 27, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
To determine whether people with long COVID exhibit microbial dysbiosis characterized by decreased bacterial diversity, overgrowth of Bacteroides taxa, and lower SCFA, indole, and secondary bile acid production with biospecimen collections
At baseline until final values
Secondary Outcomes (1)
To collect matched stool, blood, and intestinal biopsy samples from a cohort of 300 individuals with and without long COVID (150/group)
At baseline until final values
Other Outcomes (4)
Viral persistence of SARS-CoV-2 in intestinal biopsies (RNAScope).
At baseline until final values
Composition of microbial taxa in stool (shotgun metagenomics)
At baseline until final values
Generation of colonic organoids; determination of barrier function +/- autologous metabolites, PBMCs, T cell stimulation, Spike pseudovirus infection (BSL-2).
At baseline until final values
- +1 more other outcomes
Study Arms (2)
Subjects without Long COVID symptoms
We will enroll non-hospitalized patients recruited through the UCM long COVID clinic (headed by Dr. Rasika Karnik) and through the UCM Dept. of Gastroenterology endoscopy center under the umbrella Genesys protocol. We will also enroll convalescent subjects from the community without long COVID symptoms (only blood and stool samples collected from community participants, and they need not consent to the Genesys study to participate). All subjects will have had at least 1 PCR- or antigen-confirmed COVID-19 infection within the past 3 years and will be at least 60 days from their last SARS-CoV-2 infection.
Subjects with Long COVID symptoms
We will enroll non-hospitalized patients recruited through the UCM long COVID clinic (headed by Dr. Rasika Karnik) and through the UCM Dept. of Gastroenterology endoscopy center under the umbrella Genesys protocol. We will also enroll convalescent subjects from the community with long COVID symptoms (only blood and stool samples collected from community participants, and they need not consent to the Genesys study to participate). All subjects will have had at least 1 PCR- or antigen-confirmed COVID-19 infection within the past 3 years and will be at least 60 days from their last SARS-CoV-2 infection.
Interventions
To collect biospecimens (matched stool \& blood) samples from 400 people with and without long COVID (200 participants/group) to understand how COVID-induced dysbiosis impacts symptom severity, immune suppression, and gut barrier dysfunction both ex vivo and in vitro.
Eligibility Criteria
We will enroll non-hospitalized patients recruited through the UCM long COVID clinic (headed by Dr. Rasika Karnik) and through the UCM Dept. of Gastroenterology endoscopy center under the umbrella Genesys protocol. We will also enroll convalescent subjects from the community with and without long COVID symptoms (only blood and stool samples collected from community participants, and they need not consent to the Genesys study to participate). All subjects will have had at least 1 PCR- or antigen-confirmed COVID-19 infection within the past 3 years and will be at least 60 days from their last SARS-CoV-2 infection. We will recruit a total of 400 subjects (200 ea. w/ and w/o long COVID). The research will be conducted at UCM clinic sites and in laboratory facilities
You may qualify if:
- Age: 18-80
- Sex: Any
- Race: Any
- Last COVID infection: within past 3 years, PCR- or antigen-confirmed, symptomatic (mild/moderate/severe)
- COVID vaccination status: Any
- Presence of long COVID symptoms (GI, cardiac, pulmonary, neuro, musculoskeletal, and/or psych): 200 with symptoms, 200 w/o symptoms as defined by SBQ-LCTM.
- May or may not be doing routine endoscopy at UCM
You may not qualify if:
- Age \<18 or \>80
- Last COVID infection \>3 years ago (PCR/antigen-confirmed, symptomatic)
- Currently or within the last 3 months COVID+ by nasopharyngeal PCR/antigen test
- Currently diagnosed with cancer
- Currently pregnant (cannot take colon biopsy sample; only eligible for survey/blood \& stool collection)
- Currently on biologic immunomodulatory medications
- Official diagnosis of irritable bowel disease (IBD) or other chronic GI disorder
- Vulnerable and/or Special Populations
- Healthy adult volunteers
- Pregnant people
- UCMC and UChicago employees
- Staff/faculty
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
The University of Chicago
Chicago, Illinois, 60637, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lavanya Visvabharathy, Ph.D
University of Chicago
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2025
First Posted
February 13, 2025
Study Start
January 21, 2025
Primary Completion (Estimated)
January 1, 2029
Study Completion (Estimated)
January 1, 2029
Last Updated
March 2, 2026
Record last verified: 2026-02