COVID-19 and the digestive system: A comprehensive review
Open accessAbstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading at an alarming rate, and it has created an unprecedented health emergency threatening tens of millions of people worldwide. Previous studies have indicated that SARS-CoV-2 ribonucleic acid could be detected in the feces of patients even after smear-negative respiratory samples. However, demonstration of confirmed fecal-oral transmission has been difficult. Clinical studies have shown an incidence rate of gastrointestinal (GI) symptoms ranging from 2% to 79.1% in patients with COVID-19. They may precede or accompany respiratory symptoms. The most common GI symptoms included nausea, diarrhea, and abdominal pain. In addition, some patients also had liver injury, pancreatic damage, and even acute mesenteric ischemia/thrombosis. Although the incidence rates reported in different centers were quite different, the digestive system was the clinical component of the COVID-19 section. Studies have shown that angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, was not only expressed in the lungs, but also in the upper esophagus, small intestine, liver, and colon. The possible mechanism of GI symptoms in COVID-19 patients may include direct viral invasion into target cells, dysregulation of angiotensin-converting enzyme 2, immune-mediated tissue injury, and gut dysbiosis caused by microbiota. Additionally, numerous experiences, guidelines, recommendations, and position statements were published or released by different organizations and societies worldwide to optimize the management practice of outpatients, inpatients, and endoscopy in the era of COVID-19. In this review, based on our previous work and relevant literature, we mainly discuss potential fecal-oral transmission, GI manifestations, abdominal imaging findings, relevant pathophysiological mechanisms, and infection control and prevention measures in the time of COVID-19.
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Several studies showed the important role of IL-1 in endothelial dysfunction, inflammation, and thrombi formation in COVID-19 patients by stimulating the production of Thromboxane A2 (TxA2) and thromboxane B2 (TxB2).
“Several studies showed the important role of Il-1 in endothelial dysfunction, inflammation, and thrombi formation in COVID-19 patients by stimulating the production of Thromboxane A2 (TxA2) and thromboxane B2 (TxB2).”
From Acute mesenteric ischemia in COVID-19 patients (2021) · cites this paper as [80]
These findings may justify the recommendation for an IL-1 receptor antagonist (IL-1Ra) which can prevent hemodynamic changes, septic shock, organ inflammation, and vascular thrombosis in severe forms of COVID-19 patients.
“These findings may justify the recommendation for an IL-1 receptor antagonist (IL-1Ra) which can prevent hemodynamic changes, septic shock, organ inflammation, and vascular thrombosis in severe forms of COVID-19 patients [80,81,82].”
From Acute mesenteric ischemia in COVID-19 patients (2021) · cites this paper as [80]
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The Digestive System and the COVID-19
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SARS‐CoV‐2 infection and multi-organ system damage: A review
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BackgroundMelatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions
Ieșanu, M. I., Zahiu, C. D. M., Dogaru, I.-A., Chiţimuș, D. M., Pîrcălăbioru, G. G., Voiculescu, S. E., Isac, S., Galoş, F., Pavel, B., O’Mahony, S. M., et al. (2022) · Antioxidants · doi:10.3390/antiox11112244 · Cited by 60 · see citing works
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“This probably reflects the clinical component of the increased prevalence of gastrointestinal symptoms in COVID-19 infection [20].”
BackgroundAcute mesenteric ischemia in COVID-19 patients
Serban, D., Tribus, L. C., Vancea, G., Stoian, A. P., Dascalu, A. M., Suceveanu, A. I., Tanasescu, C., Costea, A. C., Tudosie, M. S., Tudor, C., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm11010200 · Cited by 46 · see citing works
“Thromboprophylaxis with enoxaparin could be also recommended to ambulatory patients with mild to moderate forms of COVID-19 if the results of prospective studies show statistically relevant benefits [80].”
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“Some gastrointestinal and hepatobiliary sequelae have been reported in COVID‐19 survivors, such as post‐infectious irritable bowel syndrome and dyspepsia.[145]”
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“The high mortality rate in our study may also have been compounded due to other coexisting conditions in patients with COVID-19 resulting in delay in the diagnosis and management [20].”
BackgroundAlcohol use disorder as a potential risk factor for COVID ‐19 severity: A narrative review
Forsyth, C. B., Voigt, R. M., Swanson, G. R., Bishehsari, F., Shaikh, M. W., Zhang, L., Engen, P. A., & Keshavarzian, A. (2022) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14936 · Cited by 18 · see citing works
Tea Polyphenols Prevent and Intervene in COVID-19 through Intestinal Microbiota
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“97% of patients with new coronary pneumonia with gastrointestinal symptoms were severely or critically ill [98].”
BackgroundHealth management of patients with COVID-19: is there a room for hydrotherapeutic approaches?
Bailly, M., Evrard, B., Coudeyre, E., Rochette, C., Mériade, L., Blavignac, C., Fournier, A.-C., Bignon, Y., Dutheil, F., Duclos, M., et al. (2022) · International Journal of Biometeorology · doi:10.1007/s00484-022-02246-w · Cited by 10 · see citing works
COVID-19 and diarrhea: putative mechanisms and management
Juthi, R. T., Sazed, S. A., Sarmin, M., Haque, R., & Alam, M. S. (2022) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2022.11.018 · Cited by 10 · see citing works
Severity of COVID-19 in Patients with Diarrhoea: A Systematic Review and Meta-Analysis
Dhakal, S., Charoen, P., Ngum, W. P., Luvira, V., Sivakorn, C., Hanboonkunupakarn, B., Chirapongsathorn, S., & Poovorawan, K. (2023) · Tropical Medicine and Infectious Disease · doi:10.3390/tropicalmed8020084 · Cited by 9 · see citing works
“In COVID-19 patients, SARS-CoV-2 infection can cause gut dysbiosis by altering the intestinal microbiota which affect gut microbiota composition [5].”
InfluentialAljaaly, E. A., & Khatib, M. A. (2024) · Diagnostics · doi:10.3390/diagnostics14151630 · Cited by 10 · see citing works
“…invasion of the gastrointestinal tract, increased fecal calprotectin, presence of viral RNA in feces, altered intestinal permeability, gut microbiota dysbiosis, mucosal damage on gastrointestinal endoscopy, and involvement of enteric nervous system mechanisms that lead to FGID development [10].”
BackgroundResultZheng, L., Zhang, L., Zheng, Y., An, J., Wen, G., Jin, H., & Tuo, B. (2023) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2023.5222 · Cited by 8 · see citing works
“Nausea was associated with the first case of COVID‑19 in both China and the USA (41).”
InfluentialAhsan, K., Anwar, M. A., & Munawar, N. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i11.1708 · Cited by 8 · see citing works
Al-Momani, H., Aolymat, I., Almasri, M., Mahmoud, S. A., & Mashal, S. (2023) · Future Science OA · doi:10.2144/fsoa-2023-0040 · Cited by 8 · see citing works
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Role of nutrition in diabetes mellitus and infections
Yu, X.-L., Zhou, L., Huang, X. J., Li, X., Wang, M., & Yang, J. (2024) · World Journal of Clinical Cases · doi:10.12998/wjcc.v13.i3.94389 · Cited by 7 · see citing works
Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains
Rhodes, R. H., Love, G. L., Lameira, F. D. S., Shahmirzadi, M. S., Fox, S., & Heide, R. S. V. (2024) · Diagnostic Pathology · doi:10.1186/s13000-024-01445-w · Cited by 9 · see citing works
Investigating the trajectory of post-COVID impairments: a longitudinal study in Sweden
Badinlou, F., Abzhandadze, T., Rahimian, F., Jansson‐Fröjmark, M., Hedman‐Lagerlöf, M., & Lundgren, T. (2024) · Frontiers in Psychology · doi:10.3389/fpsyg.2024.1402750 · Cited by 6 · see citing works
Zhang, S., Yan, Z., Zhang, Y., Wu, X., Liu, L., Yang, A., & Duan, M. (2023) · BMJ Open · doi:10.1136/bmjopen-2022-068291 · Cited by 5 · see citing works
SARS-CoV-2 Variant-Specific Gastrointestinal Symptoms of COVID-19: 2023 Update
Slabakova, Y., Gerasoudis, S., Miteva, D., Peshevska-Sekulovska, M., Batselova, H., Snegarova, V., Vasilev, G., Vasilev, G., Sekulovski, M., Lazova, S., et al. (2023) · Gastroenterology Insights · doi:10.3390/gastroent14040032 · Cited by 5 · see citing works
Wang, C.-H., Yang, J., Chen, C., Su, S.-H., Yu, H.-Y., Juan, Y., Chiu, Y., & Ho, T. (2024) · Tzu Chi Medical Journal · doi:10.4103/tcmj.tcmj_267_23 · Cited by 5 · see citing works
“Studies have reported that SARS-CoV-2 mainly infects the lungs and other organs, such as the kidneys and heart [2,9].”
BackgroundCurrent Views About the Link between SARS-CoV-2 and the Liver: Friends or Foe?
Lovero, R., Charitos, I. A., Topi, S., Castellaneta, F., Cazzolla, A. P., & Colella, M. (2023) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/0118715303251985231009050626 · Cited by 3 · see citing works
Мосійчук, Л. М. (2022) · Український медичний часопис · doi:10.32471/umj.1680-3051.150.232527 · Cited by 3 · see citing works
Nunes, B. B. D. S., Mendonça, J. D. S., de Matos, L. P., Guimarães, A. T. B., Soares, W. R., Rodrigues, A. S. D. L., Govindarajan, M., Gomes, A. R., da Luz, T. M., & Malafaia, G. (2025) · Environmental Science and Pollution Research · doi:10.1007/s11356-024-35840-z · Cited by 2 · see citing works
“…the ingestion of SARS-CoV-2 lysate protein does not trigger, in these organs, responses similar to those observed in humans infected with SARS-CoV-2 (Wang et al. 2021a; Abdullaev et al. 2021; Anastasio et al. 2021; Lins & Smaniotto 2021; Halawa et al. 2022; Jansen et al. 2022; Zhang et al. 2023).”
Shah, S. C., Canakis, A., Halvorson, A. E., Dorn, C., Wilson, O., Denton, J., Hauger, R., Hunt, C., Suzuki, A., Matheny, M. E., et al. (2022) · Gastro Hep Advances · doi:10.1016/j.gastha.2022.06.015 · Cited by 2 · see citing works
“Angiotensin-converting enzyme II receptors are concentrated on type 2 alveolar cells and intestinal epithelial cells, 6 with the small intestine exhibiting a 10-fold higher tissue concentration than the lungs.”
BackgroundMesenteric ischemia: a case of extrapulmonary presentation in COVID-19
Salpekar, R., & Krishna, S. M. (2022) · Annals of African Surgery · doi:10.4314/aas.v20i1.6 · Cited by 1 · see citing works
Patterns of Gastrointestinal Symptoms of Covid-19 Patients in a University Hospital of Bangladesh
Islam, S., Islam, S., Tabassum, N., Islam, N., Tarik, I., & Alam, M. R. (2024) · Bangabandhu Sheikh Mujib Medical College Journal · doi:10.3329/bsmmcj.v3i1.71913 · Cited by 1 · see citing works
A Series of COVID-19 Cases With Findings in the Gastrointestinal and Hepatobiliary System
Wu, D., Hacking, S. M., & Lee, L. (2022) · Cureus · doi:10.7759/cureus.22602 · Cited by 1 · see citing works
“Approximately 25% of infected patients have gastrointestinal symptoms including nausea, vomiting, and diarrhea, with up to 39% of patients having elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels [2].”
BackgroundPrognostic Role of Clinical Features of Moderate Forms of COVID-19 Requiring Hospitalization
Trofor, A. C., Cernomaz, A. T., Lotrean, L. M., Crișan-Dabija, R. A., Peñalvo, J. L., Melinte, O. E., Popa, D. R., & Man, M. A. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13060900 · Cited by 1 · see citing works
“Immune-mediated mucosal lesions and alterations to the gut microbiota have also been considered [37].”
BackgroundGaba, A., Nambi, N. K., & Joshi, A. (2022) · Global Journal of Health Science · doi:10.5539/gjhs.v14n7p1 · Cited by 1 · see citing works
“, 2021), gastrointestinal disorders (Aguila et al., 2020; Hunt et al., 2021; Kostoff et al., 2021; Wang et al., 2021), liver disease (Cha, Regueiro, & Sandhu, 2020; Levy et al.”
BackgroundRibeiro, I. B., de Moura, D. T. H., & de Moura, E. G. H. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i37.6345
Extrapulomnary-extragastrointestinal manifestations in patients with COVID-19
Soliman, G. M. M., El-Dessouky, Y. M. M., & Mohamed, R. S. (2022) · International Journal of Health Sciences · doi:10.53730/ijhs.v6ns4.8190
Bedock, D., Faucher, P., & Oppert, J. (2022) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2022.07.002
“En effet, tous les mécanismes favorisant la dénutrition peuvent être présents : les symptômes respiratoires et sensoriels (dyspnée, dysphagie, dysgueusie, anosmie, anorexie), présents chez 30 à 70 % des patients hospitalisés pour COVID-19, réduisent la prise alimentaire, les symptômes généraux et digestifs (sueurs, na…”
BackgroundIntestinal ischemia in COVID-19 patients: A case series
Winkel, T. V. D., Janssens, W., Messaoudi, N., Schoneveld, M., Stijns, J., Eetvelde, E. V., & Jansen, Y. J. (2023) · Case Reports International · doi:10.5348/100113z06tw2023cs
Каночкина, М. С., & Sokolov, I. R. (2022) · Хранение и переработка сельхозсырья · doi:10.36107/spfp.2022.332
Spare a thought for swallowing
Allen, J. E. (2023) · Current Opinion in Otolaryngology & Head & Neck Surgery · doi:10.1097/moo.0000000000000923
Freshwater Pollution by Sars-Cov-2 Lysate Protein Induces Multiple Impacts on C57bl/6j Female MicePreprint
Nunes, B. B. D. S., Mendonça, J. D. S., de Matos, L. P., Guimarães, A. T. B., Matos, S. G. D. S., de Souza, S. S., Rodrigues, A. S. D. L., Islam, A. R. M. T., Govindarajan, M., Mujawar, M., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4789640
Upper and lower gastrointestinal symptoms and manifestations of COVID-19
Woods, B., Mehta, P. D., Jagirdhar, G. S. K., Kashyap, R., & Bansal, V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18703-2.00008-6
COVID-19 and Digestive Diseases: A Comprehensive Review on Pathophysiology and Clinical Management
Ibrahim, N. E., & Hassan, F. M. (2024) · Coronaviruses · doi:10.2174/0126667975293524240625115448
Kaverina, A. A., Вавринчук, С. А., & Kosenko, P. M. (2024) · Clinical Medicine (Russian Journal) · doi:10.30629/0023-2149-2024-102-4-360-366
Effect of COVID-19 on the Gut Microbiota of Pregnant Women (review)
Bembeeva, B. O., Priputnevich, T. V., & Dolgushina, N. V. (2024) · Epidemiology and Vaccinal Prevention · doi:10.31631/2073-3046-2024-23-5-92-98
Inasiyyah, R., Kusuma, I. Y., Fauziah, F., Nurkholis, F., & Kurniasih, K. I. (2025) · International Journal of Gastrointestinal Intervention · doi:10.18528/ijgii240083
Hunger, R., König, V., Stillger, R., & Mantke, R. (2022) · Figshare · doi:10.6084/m9.figshare.20175732
Hunger, R., König, V., Stillger, R., & Mantke, R. (2022) · Figshare · doi:10.6084/m9.figshare.20175735
Eosinophil-associated intestinal immune responses following SARS-CoV-2 infection in K18-hACE2 mice
Tamaki, S., Kawashima, R., Uematsu, T., Kawakami, F., Imai, M., Kurosaki, Y., Matsumoto, T., Maehana, S., Hara, Y., Sugawara, S., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0355607
“Together, these observations indicate that the GI tract plays an important role in the heterogeneous clinical presentation of COVID-19 [1,4,5].”
InfluentialYu, X., Xiang, Y., Lv, S., Wang, X., Liu, N., Yan, X., Liu, Y., Yan, X., Shi, J., & Wang, M. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1017022
- Authors
- Wang, M.-K., Yue, H.-Y., Cai, J., Zhai, Y.-J., Peng, J.-H., Hui, J.-F., Hou, D.-Y., Li, W.-P., & Yang, J.-S.
- Affiliations
- Second Military Medical University (CN)
- ORCID
- Cai, Jin
- Venue
- World Journal of Clinical Cases
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2021-06-06
- Volume
- 9
- Issue
- 16
- Pages
- 3796-3813
- ISSN
- 2307-8960 (ISSN-L)
- PMC
- PMC8180220
- OpenAlex
- W3162527482
- Cited by
- 50
- References
- 134
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 11 · 2023: 11 · 2022: 19 · 2021: 5
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Clinical Cases (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Dermatology › Dermatological and COVID-19 studies
- Keywords
- COVID-19 pandemic, SARS-CoV-2, gastrointestinal symptoms, fecal-oral transmission, ACE2 receptor, gut dysbiosis, liver injury, acute mesenteric ischemia, abdominal imaging findings, infection control, diarrhea, nausea
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