In a recent article published in the journal Biomedicines, a team of Italian scientists has presented case reports of five coronavirus disease 2019 (COVID-19) patients undergoing emergency surgery for intestinal ischemia.
The case reports highlight that the histopathological changes observed in the intestine of COVID-19 patients are similar to that observed in the lung, which is the primary target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Background
The gastrointestinal pathologies associated with SARS-CoV-2 infection are believed to be triggered by multiple factors. The presence of gastrointestinal symptoms has been observed in about 40% of COVID-19 patients. Regarding mode of action, studies have suggested that SARS-CoV-2 uses transmembrane serine protease TMPRSS2 to enter and replicate inside the gastrointestinal (GI) tract. In addition, the virus could translocate from the respiratory tract to the GI tract through blood circulation.
However, there is no clear evidence whether intestinal damages are associated with direct viral replication or SARS-CoV-2-induced hyper-coagulation.
In the current study, scientists have described case reports of five COVID-19 patients who had developed intestinal ischemia.
Important observations
The study included COVID-19 patients who were undergoing surgery for intestinal ischemia between March 2020 and May 2021 at the Emergency Surgery and Trauma Center Department of the University of Pisa, Italy.
The first patient was a 74-year-old man with a history of hypertension and ischemic heart disease. Three days after COVID-19 diagnosis, the patient was intubated and shifted to the intensive care unit (ICU) because of developing dyspnea, severe desaturation, vomiting, and coma. He also experienced acute abdominal distension. The findings of CT scan and laparotomy indicated ischemic intestinal alterations. The surgical removal of the cecum (a part of the large intestine) along with the terminal ileum (the last part of the small intestine) was performed. The histological analysis of surgically-removed ileum and cecum revealed ischemic necrosis of the mucosal layer and intestinal pneumatosis.
The second patient was a 69-year-old man with a history of hypertension and subdural hematoma. The CT scan and laparotomy findings indicated intestinal perforation. The surgical removal of the jejunum (the middle part of the small intestine) and subsequent anastomosis was performed. The histological analysis revealed thickening of the intestinal wall, edema formation, and intestinal pneumatosis.
The third patient was a 77-year-old man with a history of cardiovascular, pulmonary, and metabolic disorders. The clinical findings indicated ischemic intestinal perforation. The surgical removal of the one side of the colon along with ileostomy mucous fistula was performed.
The fourth patient was 75-year-old man with a history of myocardial infarction and gastric ulcer. The CT scan and laparotomy findings revealed intestinal perforation and interstitial pneumonia. Based on the clinical findings, a resection anastomosis was performed.
The fifth patient was a 72-year-old man with a history of hypertension, post-ischemic dilated heart disease, atrial fibrillation, dyslipidemia, and chronic obstructive pulmonary disease. He was hospitalized due to COVID-19 related interstitial pneumonia. The endoscopic and CT scan findings showed a clot and active arterial endoluminal bleeding in the duodenum. Despite administration of angioembolization (a medical procedure to reduce blood loss), the patient repeatedly experienced active intestinal bleeding.
A series of surgical procedures were performed to prevent the bleeding and repair the damage.
During the post-surgical phase, the patient developed sepsis and peritonitis. On day 10 post-surgery, he died due to septic shock. The analysis of surgically-removed intestinal samples showed dilated small intestinal wall and attenuated mucosa with fibrin stratification. In addition, ischemic necrosis and mucosal, muscular, and adipose tissue ulceration were detected.
The peritoneal fluid collected from the patients during surgery was negative for SARS-CoV-2. The immunohistochemical and molecular analysis of patient-derived intestinal tissues showed weak intensity expression of SARS-CoV-2-specific spike and nucleocapsid proteins in four out of five patients. A strong expression of virus-specific proteins was observed only in the third patient. Importantly, all patients showed infiltration of immune cells in the intestinal blood vessels and interstitial edema in the small intestine and colon.
Study significance
The study highlights that gastrointestinal manifestation in COVID-19 patients may or may not be associated with respiratory or systemic symptoms. Although SARS-CoV-2 positivity in the intestinal tissue has been detected in only one patient, endothelial inflammation observed in the intestinal vessels of all patients suggests a microvascular small intestinal injury. These clinical features are similar to that observed in the small blood vessels of COVID-19-affected lungs.
Overall, the study findings indicate that SARS-CoV-2 induces lung and intestinal damage through a similar mode of action. Given the study findings, the scientists suggest that physicians should carefully monitor the presence of SARS-CoV-2 infection in the intestine of COVID-19 patients in order to avoid severe and fatal outcomes of ischemic intestinal perforation.
