Viral Antigen Persistence Linked to “Long-Haul COVID” in Patients With Inflammatory Bowel Disease

Young Caucasian woman sitting inside of a medical clinic, telling her complaints to the doctor about the pain she feels in her stomach, both wearing protective face masks
Researchers assessed whether the persistence of viral antigens of COVID-19 in the gut mucosa of patients with IBD was associated with postacute sequelae of SARS-CoV-2 infection.

Most patients with inflammatory bowel disease (IBD) who recovered from COVID-19 and were experiencing postacute sequelae of SARS-CoV-2 infection — also referred to as “long-haul COVID” —  were found to have signs of SARS-CoV-2 in their gut tissues, according to study findings published in Gastroenterology.

Patients (N=46) with IBD who had confirmed SARS-CoV-2 infection were recruited at the Medical University Innsbruck in Austria. Patients underwent upper and lower endoscopy an average of 7.3 (range, 94-257) months after infection. Retrieved gut tissue samples were phenotyped, underwent RNA testing, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), interferon gamma release assay (IGRA), and virus cultivation to assess for the presence of SARS-CoV-2.

The patient population included 56.5% men, the median age was 44.67 (IQR, 28.11-51.95) years, 67.4% had Crohn disease, 28.3% had ulcerative colitis, and 58.7% were in remission.

Most patients (n=32) tested positive for mucosal SARS-CoV-2. Patients with mucosal SARS-CoV-2 had shorter IBD duration (median, 24.96 vs 35.51 years; P =.02) and fewer were using medication at endoscopy (0.0% vs 14.3%; P =.03).

Stratified by tissue sample location (duodenum, ileum, and colon), 4 of the patients tested positive at all 3 locations, 9 tested positive at 2 locations, 19 at 1 location, and 14 at no locations. Viral RNA was detected in 31% of biopsies, RNA-dependent RNA polymerase in 13.6%, the Spike protein in 11.4%, the Nucleocapsid protein in 10.6%, and the Envelope protein in 6.1%.

No patient who tested negative for mucosal SARS-CoV-2 had long-haul COVID symptoms, whereas 65.6% of the cohort that tested positive had any postacute symptom (P =.001). The most common symptoms were fatigue (56.3%), memory issues (43.8%), loss of smell (34.4%), abdominal pain (28.1%), sleeping disorders (25.0%), persistent cough (21.9%), and shortness of breath (21.9%), among others.

Testing positive for mucosal SARS-CoV-2 was unrelated to fecal calprotectin (P =.40).

Study limitations included a small sample size. The findings should be confirmed in a larger, controlled trial, according to the study authors.

“Collectively, we provide evidence for SARS-CoV-2 antigen persistence in the gut as a basis for immune perturbation in postacute COVID-19,” the study authors wrote.


Zollner A, Koch R, Jukic A, et al. Post-acute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases. Gastroenterology. Published online May 1, 2022. doi:10.1053/j.gastro.2022.04.037