Abstract
Persistent gastrointestinal (GI) symptoms are increasingly recognized as part of long COVID, yet their underlying mechanisms remain poorly defined. We conducted an exploratory case-series study of 80 adults hospitalized with severe COVID-19 in March-May 2020 in Manaus, Brazil. Two years post-infection, participants underwent structured clinical interviews and longitudinal cytokine analysis (IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α). Overall, 30 participants reported ongoing GI symptoms (GI group) predominantly gastroesophageal reflux (63%), abdominal pain (43%), and diarrhea (37%). Compared with participants without GI symptoms (nGI group, n = 50), the GI group reported a higher burden of additional long COVID symptoms, including palpitations, headache, and arthralgia. They also exhibited distinct clinical and laboratory features, including lower baseline creatinine and ferritin levels and altered platelet indices. Although IL-6 levels were lower during the acute hospitalization phase, they became significantly elevated at four months post-infection (D120, p = 0.005), suggesting delayed inflammatory response. Ascendent biomarker analysis identified TNF-α as highly expressed in a large proportion of GI group. The findings suggest GI problems can persist two years after severe COVID-19, and long-term inflammatory dysregulation may underlie the pathogenesis of these GI manifestations in long COVID. Prolonged gastrointestinal surveillance in COVID-19 survivors is necessary.
Data availability
All data generated or analyzed during for this study are included in this published article. Additional information or data regarding the study can be availed upon reasonable request.
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Acknowledgements
We thank all the patients and families who participated in this study, as well as the clinical and laboratory staff of Hospital Delphina Rinaldi Abdel Aziz, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas and Fundação de Medicina Tropical Dr. Heitor Vieira Dourado for their support during patient recruitment and follow-up. We are also grateful to the research groups whose data contributed to this cohort.
Funding
This study was supported by a research fund from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (Funding Code 001 and CAPES/PROAP 1247/2022); the Fundação de Amparo a Pesquisa do Estado do Amazonas (FAPEAM) (Call No. 006/2020 – PCTI-EMERGESAÚDE/AM – Priority Areas and Call No. 038/2022 - PDPG/CAPES/FAPEAM) and FAPEAM undergraduate research scholarships awarded to student collaborators involved in this project. Support was also obtained from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (CNPq/MCTI/ CT-Saude Call – Research, development and innovation in long COVID); notice n°53/2022 (RECLAIM Brazil Study), and a CNPq PDJ scholarship to author VIM (175855/2023-4). GCM, WMM, VSS and AGC are grateful to CNPq for their research fellowship (Produtividade Program).
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**A.S.P: ** Conceptualization, Investigation, Writing – original draft, Writing – review & editing, Investigation, Data analysis, curation and visualization. **V.I.M: ** Conceptualization, Writing – original draft, Writing – review & editing, Data analysis, curation and visualization. **J.C.F.N: ** Writing – review & editing, Data analysis, curation and visualization. **A.B.S.M: ** Conceptualization, Writing – original draft, Writing – review & editing, Investigation, Data analysis, curation and visualization. **A.V.S.N** : Data analysis, curation, and visualization. **J.S.V** : Investigation, Methodology. **G.C.d.M: ** Conceptualization, Resources, Writing – review & editing. **W.M.M: ** Conceptualization, Writing – review & editing. **V.S.S: ** Supervision, Data analysis, curation. **A.G.C: ** Conceptualization, Supervision and coordination, Investigation, Funding, Resources, Writing – review & editing. **F.F.A.V: ** Conceptualization, Supervision, Funding acquisition, Resources, Validation, Writing – review & editing. All authors read and approved the final version of the manuscript.
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dos Santos Pinto, A., Mwangi, V.I., Neves, J.C.F. et al. Clinical features and inflammatory signatures of patients with persistent gastrointestinal long COVID two years after severe SARS-CoV-2 infection. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37595-8
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DOI: https://doi.org/10.1038/s41598-026-37595-8