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Clinical features and inflammatory signatures of patients with persistent gastrointestinal long COVID two years after severe SARS-CoV-2 infection
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  • Published: 29 January 2026

Clinical features and inflammatory signatures of patients with persistent gastrointestinal long COVID two years after severe SARS-CoV-2 infection

  • Arlene dos Santos Pinto1,2,
  • Victor Irungu Mwangi1,2,
  • Juliana Costa Ferreira Neves1,3,
  • Alex Bezerra Silva Maciel1,2,
  • Alexandre V. Neto1,2,
  • Jefferson da Silva Valente1,2,
  • Gisely Cardoso de Melo1,2,
  • Wuelton Marcelo Monteiro1,2,
  • Vanderson de Souza Sampaio1,5,
  • Allyson Guimarães da Costa1,2,3,4 &
  • …
  • Fernando F. Almeida-Val1,2,6 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Gastroenterology
  • Immunology
  • Medical research

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).

Author information

Authors and Affiliations

  1. Programa de Pós-Graduação em Medicina Tropical (PPGMT), Universidade do Estado Do Amazonas, Manaus, 69040-000, AM, Brazil

    Arlene dos Santos Pinto, Victor Irungu Mwangi, Juliana Costa Ferreira Neves, Alex Bezerra Silva Maciel, Alexandre V. Neto, Jefferson da Silva Valente, Gisely Cardoso de Melo, Wuelton Marcelo Monteiro, Vanderson de Souza Sampaio, Allyson Guimarães da Costa & Fernando F. Almeida-Val

  2. Fundação de Medicina Tropical Dr. Heitor Veira Dourado, Manaus, 69040-000, AM, Brazil

    Arlene dos Santos Pinto, Victor Irungu Mwangi, Alex Bezerra Silva Maciel, Alexandre V. Neto, Jefferson da Silva Valente, Gisely Cardoso de Melo, Wuelton Marcelo Monteiro, Allyson Guimarães da Costa & Fernando F. Almeida-Val

  3. Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, 69050-001, AM, Brazil

    Juliana Costa Ferreira Neves & Allyson Guimarães da Costa

  4. Programa de Pós-graduação em Imunologia Básica e Aplicada (PPGIBA), Universidade Federal do Amazonas, Manaus, 69080-900, AM, Brazil

    Allyson Guimarães da Costa

  5. Instituto Todos Pela Saúde, São Paulo, 01310-942, SP, Brazil

    Vanderson de Souza Sampaio

  6. Universidade Federal do Amazonas, Manaus, 69077-000, AM, Brazil

    Fernando F. Almeida-Val

Authors
  1. Arlene dos Santos Pinto
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  2. Victor Irungu Mwangi
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  3. Juliana Costa Ferreira Neves
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  7. Gisely Cardoso de Melo
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Contributions

**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.

Corresponding authors

Correspondence to Allyson Guimarães da Costa or Fernando F. Almeida-Val.

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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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  • Received: 14 August 2025

  • Accepted: 23 January 2026

  • Published: 29 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-37595-8

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Keywords

  • Long COVID
  • Gastrointestinal symptoms
  • Inflammation
  • SARS-CoV-2
  • Brazil
  • COVID-19
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