Gastrointestinal Manifestations of SARS-CoV-2: A Comprehensive Examination of Mesenteric Ischemia

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The ongoing COVID-19 pandemic has presented an unprecedented challenge to the global healthcare community. While the respiratory symptoms of the SARS-CoV-2 virus have dominated the spotlight, there is growing evidence to suggest that the virus can affect various other organ systems, including the gastrointestinal (GI) tract.

In this article, we will delve into the intricate relationship between SARS-CoV-2 infection and GI symptoms, particularly focusing on the rare but severe complication of mesenteric ischemia.

GI Symptoms in COVID-19

GI symptoms such as nausea, anorexia, vomiting, and diarrhea have been recognized as common among SARS-CoV-2 infected patients. These symptoms, often overshadowed by respiratory distress, have raised questions about the virus’s multi-faceted impact on the human body (1, 2).

One noteworthy aspect of SARS-CoV-2’s involvement with the GI tract is the presence of viral shedding in stool samples. This viral presence may contribute to the onset of GI symptoms, though the exact mechanisms remain under investigation (3).

Furthermore, the virus has been detected in other specimens, such as the gallbladder, during cholecystectomy procedures, suggesting a broader affinity for the GI system (4, 5). Acute replication of the virus within the GI tract has also been demonstrated in some studies (6).

Liver enzyme abnormalities are a common finding in COVID-19 patients with GI symptoms. However, it is the atypical presentations that warrant significant attention. Conditions like acute cholecystitis, acute pancreatitis, ileus, pseudo-colonic obstruction, mesenteric ischemia, and bowel necrosis, while rare, have been associated with high morbidity and mortality rates. In particular, bowel necrosis has a staggering mortality rate of 50% (7–12).

Mesenteric Ischemia in COVID-19

Mesenteric ischemia is a condition characterized by inadequate blood supply to the intestine, leading to tissue damage and, if untreated, necrosis. This condition is often reported by critically ill COVID-19 patients and is associated with a distinct set of symptoms, including abdominal pain, nausea, vomiting, and per-rectal bleeding. Distension and tenderness are typical features of peritonism, which may indicate advanced disease (13).

Laboratory findings play a crucial role in the diagnosis and assessment of mesenteric ischemia. While the importance of these findings is still being validated, elevated leukocyte count is observed in over 90% of patients. High lactate levels accompanied by acidosis were found in 88% of cases, with lactate levels exceeding 2 mmol/l associated with poor prognosis (14, 15).

One key marker that has shown promise in early assessment is D-dimer, which has a specificity, sensitivity, and accuracy of 82%, 60%, and 79%, respectively. D-dimer is released from fibrinolysis, making it a potentially valuable indicator in the evaluation of mesenteric ischemia (16).

Other markers, such as elevated amylase, intestinal fatty acid binding protein (I-FABP), serum alpha-glutathione S-transferase (alpha–GST), and the cobalt-albumin binding assay (CABA), have been suggested for initial diagnosis but require further validation.

The gold standard for identifying thrombus or embolus in the mesenteric arterial system (MSA) is computed tomography angiography (CTA). CTA boasts a sensitivity of 93%, specificity of 100%, and positive and negative predictive values of 100% and 94%, respectively (17, 18).

Treatment and Surgical Considerations

When mesenteric ischemia is suspected, operative intervention is often considered for bowel examination and resection. Endovascular or open angiography and thrombectomy may be necessary when proximal arterial thromboembolic disease is suspected.

Intraoperative examination of the bowel in these patients has revealed unusual findings, including patchy areas of well-demarcated yellow discoloration involving the antimesenteric bowel wall. In some cases, multiple patches varying in size from 0.5-2 cm have been observed. The terminal ileum is often the most affected area of intestinal necrosis, and the bowel may appear pale or ischemic but not frankly necrotic (19).

A unique approach in some instances involves temporarily leaving the abdomen open for a planned second-look laparotomy within 12 to 24 hours. This is recommended because ischemia can rapidly progress to transmural necrosis. However, clinical judgment may guide the decision to close the abdomen during the initial operation. Second-look laparoscopy is an emerging option worth considering (20).

Pathological examination of the resected bowel in mesenteric ischemia cases often reveals extensive mucosal ulceration, congestion with areas of extensive transmural inflammation, and transmural infarction. Additionally, fibrin microthrombi can be occasionally noted in the capillaries underlying areas of necrosis, raising the possibility of thrombosis at the submucosal vessel level (19).

Pathophysiology of Bowel Ischemia in COVID-19

Despite these observations, the precise pathophysiology of bowel ischemia in critically ill COVID-19 patients remains uncertain. It has been reported that mesenteric ischemia typically occurs when mean arterial pressure falls below 45 mmHg (21).

Patients admitted to the ICU can develop mesenteric ischemia due to factors such as high doses of vasopressors, hemodynamic instability, and metabolic derangements that compromise intestinal blood flow. This could contribute to the high rate of bowel ischemia observed in COVID-19 patients (7–10, 22).

However, some cases, like the one described in this article, do not exhibit symptoms of severe COVID-19 before the onset of abdominal pain. This suggests that SARS-CoV-2 may trigger a direct mechanism leading to bowel ischemia. The atypical features of mesenteric ischemia and the rare involvement of the watershed areas strongly suggest alternative mechanisms specific to COVID-19.

Inflammatory coagulopathy has been proposed as a possible link to mesenteric ischemia in COVID-19 patients. This coagulopathy has been associated with worse pulmonary disease, deep vein thrombosis, cerebrovascular accidents, and renal failure.

However, as of now, there is limited evidence to recommend empiric therapeutic anticoagulation for COVID-19 patients. Potential markers like D-dimer show promise but require further validation.

The Grim Reality of Mesenteric Ischemia in COVID-19

The mortality rate for COVID-19 patients who develop mesenteric ischemia is alarming, currently reported to be as high as 40%, with over 92% of deaths occurring within the immediate postoperative days due to multiorgan failure or refractory septic shock.

Conclusion

The COVID-19 pandemic has forced the medical community to adapt rapidly to an ever-evolving understanding of the disease’s manifestations. The association between SARS-CoV-2 infection and gastrointestinal symptoms, along with the severe complication of mesenteric ischemia, demonstrates the complexity of the virus’s impact on the human body.

As we continue to learn about the rare expressions of the infection and its complications, global collaboration is imperative for identifying and managing these complications effectively. Developing risk algorithms for the prevention of


reference link : https://www.researchsquare.com/article/rs-3567430/v1

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