Fatal Gastrointestinal Disorders Associated with COVID-19: Insights from GI-GVHD and MIS-A

The COVID-19 pandemic has presented numerous challenges, with severe respiratory complications being the primary focus of research and medical intervention. However, emerging evidence suggests that COVID-19 can also lead to fatal gastrointestinal (GI) disorders.

In this article, we explore the characteristics of these disorders, drawing parallels with GI graft-versus-host disease (GI-GVHD) and their potential inclusion within the multisystem inflammatory syndrome in adults (MIS-A).

GI-GVHD and its Clinical Features

GI-GVHD is a condition characterized by the immunological attack on host histocompatibility antigens by donor lymphocytes, primarily affecting the skin, liver, and GI tract. Clinical symptoms commonly include watery diarrhea, nausea, vomiting, and anorexia. The pathogenesis of GI-GVHD involves direct damage to the GI mucosa by cytotoxic T cells and tissue damage mediated by cytokines.

Imaging findings, such as contrast-enhanced CT, reveal abnormal mucosal enhancement in patchy or diffusely thickened bowel segments, particularly in the small intestine. Endoscopic findings encompass mucosal edema, erythema, and fragility, ranging from mild to severe manifestations.

Histopathological features of GI-GVHD comprise epithelial cell apoptosis and lymphocytic infiltration, primarily concentrated at the base of the crypt where intestinal epithelium proliferates. In mild cases, the presence of apoptotic bodies may be the sole indication for diagnosis, while severe cases exhibit crypt abscesses, crypt disappearance, and mucosal sloughing.

COVID-19 and Fatal GI Disorders

Observations of COVID-19 cases have demonstrated the development of fatal GI disorders similar to GI-GVHD. In all the cases discussed, diffuse bowel wall thickening was observed in the small intestine on CT scans. Upper GI endoscopy revealed mucosal edema in the stomach, extensive mucosal sloughing, and multiple duodenal ulcers.

Lower GI endoscopic findings displayed extensive mucosal sloughing in the small intestine, including the terminal ileum, as well as mucosal edema, sloughing, and multiple ulcers in the colon and rectum. Histological analysis showed findings consistent with GI-GVHD, including ulceration, villous atrophy, apoptotic bodies, and mucosal sloughing.

Similarities between COVID-19 and GI-GVHD

The underlying pathogenesis of both COVID-19 and GI-GVHD involves a hyperactivation of the immune response, leading to damage in various organs. The targeting of critical epithelial stem cell populations and cytokine-mediated damage plays a role in both conditions. Furthermore, the presence of extensive mucosal sloughing, elevated IL-6 expression in the small intestine and colon, and the effectiveness of steroids and infliximab in treating GI disorders associated with COVID-19 further supports the similarities to GI-GVHD.

MIS-A and Post-Infection Immune Dysregulation

The delayed onset of GI disorders in our cases suggests a post-infection immune dysregulation rather than a direct effect of SARS-CoV-2 infection. These cases align with the proposed multisystem inflammatory syndrome in adults (MIS-A), which describes a hyperinflammatory state occurring several weeks after primary COVID-19 infection. MIS-A is characterized by an exacerbation of the inflammatory response and the development of multiorgan disorders. The inclusion of these fatal GI disorders within the spectrum of MIS-A highlights the need for early diagnosis and treatment to improve patient outcomes.

Immunological Pathways and Hyperactivation

Both COVID-19 and GI-GVHD share an underlying immune dysregulation leading to tissue damage. In COVID-19, the SARS-CoV-2 virus triggers a cascade of immune responses, resulting in a hyperactivation of the immune system. Similarly, GI-GVHD arises from donor lymphocytes recognizing host histocompatibility antigens as foreign and initiating an immune response against them. This hyperactivation in both conditions leads to tissue destruction, particularly in the gastrointestinal tract.

Targeted Organs and Clinical Features

GI-GVHD predominantly affects the skin, liver, and GI tract, with the latter being the primary target. The clinical symptoms commonly observed in GI-GVHD include watery diarrhea, nausea, vomiting, and anorexia. Similarly, COVID-19 has been associated with a wide range of GI symptoms, such as diarrhea, abdominal pain, nausea, and vomiting. The overlapping clinical features suggest a common pathogenic mechanism affecting the GI system in both conditions.

GI Imaging and Endoscopic Findings

Contrast-enhanced CT scans have revealed abnormal mucosal enhancement, patchy or diffusely thickened bowel segments, and small intestine involvement in approximately 75% of GI-GVHD cases. Remarkably, similar imaging findings have been observed in COVID-19 patients with GI complications. The endoscopic findings in both conditions include mucosal edema, erythema, and fragility, further emphasizing the parallelism between COVID-19 and GI-GVHD.

Histopathological Features

Histopathological analysis plays a crucial role in elucidating the similarities between COVID-19 and GI-GVHD. GI-GVHD is characterized by apoptosis of epithelial cells and lymphocytic infiltration, with prominent involvement of the crypts. Similarly, COVID-19 patients with GI complications exhibit histological features consistent with GI-GVHD, such as epithelial cell apoptosis, villous atrophy, crypt abscesses, and mucosal sloughing. The convergence of these histopathological findings provides compelling evidence of the shared mechanisms between the two conditions.

Cytokine Storm and Tissue Damage

Both COVID-19 and GI-GVHD involve a dysregulated cytokine response, often referred to as a “cytokine storm.” In COVID-19, the excessive release of pro-inflammatory cytokines contributes to systemic inflammation and tissue damage in various organs. Similarly, GI-GVHD is mediated, in part, by cytokines that drive and amplify the disease pathogenesis. This convergence highlights the critical role of cytokines in the development of GI complications and further strengthens the analogy between the two conditions.

Implications for Diagnosis and Treatment

Recognizing the similarities between COVID-19 and GI-GVHD is of paramount importance for accurate diagnosis and appropriate management strategies. Clinicians should consider GI-GVHD in the differential diagnosis of COVID-19 patients presenting with severe GI symptoms and imaging findings consistent with GI-GVHD. Additionally, therapies effective in GI-GVHD, such as steroids and infliximab, have shown promise in treating COVID-19-associated GI complications.

Conclusion

COVID-19 can lead to fatal GI disorders with similarities to GI-GVHD. The clinical features, imaging findings, and histopathological characteristics resemble those of GI-GVHD. The hyperactivation of the immune response, cytokine-mediated damage, and the effectiveness of certain therapies further support the similarities between COVID-19-associated GI disorders and GI-GVHD.

Considering the delayed onset of these GI disorders and their association with post-infection immune dysregulation, their inclusion within MIS-A should be considered. Early diagnosis and appropriate treatment strategies are crucial to improving patient outcomes in these cases. Further research is necessary to fully understand the mechanisms underlying these fatal GI disorders associated with COVID-19 and explore potential therapeutic interventions.

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reference link :https://www.cureus.com/articles/137800-fatal-gastrointestinal-disorders-due-to-covid-19-a-case-series#!/