Dysbiosis & Long COVID

February 27, 2026 updated by: University of Chicago

DETERMINING THE IMPACT OF MICROBIAL DYSBIOSIS ON IMMUNE AND BARRIER DYSFUNCTION IN LONG COVID

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • The University of Chicago
        • Contact:
        • Contact:
          • Lavanya Visvabharathy, Ph.D
          • Phone Number: 773-834-5087
        • Principal Investigator:
          • Lavanya Visvabharathy, Ph.D
        • Sub-Investigator:
          • Rasika Karnik, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Biological: Subjects with and without Long COVID
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.
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.
Biological: Subjects with and without Long COVID
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: At baseline until final values
At baseline until final values

Secondary Outcome Measures

Outcome Measure
Time Frame
To collect matched stool, blood, and intestinal biopsy samples from a cohort of 300 individuals with and without long COVID (150/group)
Time Frame: At baseline until final values
At baseline until final values

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viral persistence of SARS-CoV-2 in intestinal biopsies (RNAScope).
Time Frame: At baseline until final values
This will only be done if participants consent to both this study and the Genesys study.
At baseline until final values
Composition of microbial taxa in stool (shotgun metagenomics)
Time Frame: At baseline until final values
At baseline until final values
Generation of colonic organoids; determination of barrier function +/- autologous metabolites, PBMCs, T cell stimulation, Spike pseudovirus infection (BSL-2).
Time Frame: At baseline until final values
This will only be done if participants consent to both this study and the Genesys study.
At baseline until final values
Assessment of T cell metabolism by flow cytometry
Time Frame: At baseline until final values
At baseline until final values

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Investigators

  • Principal Investigator: Lavanya Visvabharathy, Ph.D, University of Chicago

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2025

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

February 11, 2025

First Submitted That Met QC Criteria

February 11, 2025

First Posted (Actual)

February 13, 2025

Study Record Updates

Last Update Posted (Actual)

March 2, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB24-1178

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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