COVID-19 and pneumatosis intestinalis: An early sign of intestinal ischemia.

To the Editor,

Intestinal ischemia in association with COVID-19 had been recently reported. In this journal, Norsa et al recently described the case of a patient with extensive intestinal ischemia [1], in which they emphasized the need of clinicians to be aware of this complication and suggested the occurrence of COVID-19-induced thromboembolism in that case. Although pneumatosis intestinalis (PI) is a rare radiological sign characterized by the presence of gas in the bowel wall, it can be a sign of impending intestinal ischemia. Furthermore, the presence of portal or portomesenteric venous gas along with PI is an ominous sign indicating transmural bowel necrosis [2].

PI is generally diagnosed by abdominal radiography, especially abdominal computed tomography (CT), which reveals gas-filled cysts in the submucosa/serosa of the intestine. The pathogenesis of PI is usually explained by either mechanical theory or bacterial theory. The mechanical theory hypothesizes direct diffusion of intraluminal bowel gas through the intact intestinal mucosal membrane due to increased intraluminal pressure as in blunt trauma, ileus, or pseudo-obstruction. The bacterial theory proposes that gas-forming bacteria enter the submucosa through mucosal breaks as in bowel inflammation, infection, bowel ischemia, or necrosis [3].

COVID-19 virus can cause PI by direct injury of mucosa of the gastrointestinal tract through its attachment to the angiotensin-converting enzyme receptors (ACER2), which are abundantly expressed on enterocytes [4], or by disruption of the normal colonic gut flora or by bowel ischemia due to thromboembolic complications [5], [6], [7], [8].

Bhayana et al. reported in their radiological study about four patients with COVID-19 with pneumatosis or portal venous gas observed in abdominal CT. Three of those patients had frank bowel infarction at laparotomy, and one patient with gas in the transverse mesocolon in CT had a corresponding patchy yellow discoloration of the antimesenteric transverse colon of unknown origin [9].

Herein, we summarize a few recent reports that have described the association of PI with COVID-19 (Table 1 ) [5], [6], [7], [8]. The mean age of the patients was 59 ± 16 years, all patients were males, one of them had no comorbidities, and two patients had abdominal pain. Marked elevation of d-dimer level was observed in one patient. Extensive PI was detected in one patient in the small and large intestines, and two patients had free intraperitoneal air. Portal vein gas was prominent in one patient, and although surgery was indicated in this patient, a conservative approach was undertaken as the blood flow was normal in the superior mesenteric artery origin, and the patient recovered. One patient had renal transplantation and multiple comorbidities; however, his condition improved with the conservative management. In all patients, conservative management with bowel rest, antibiotics, intravenous fluid, or heparin infusion was successful.

Table 1

Characteristics of COVID -19 patients with pneumatosis intestinalis.

	Lakshmanan and Toubia [5]	Meini et al [6]	Kietly et al [7]	Aiello et al [8]
Age, sex	72, male	44, male	47, male	73, male
Medical history of comorbidities	Multiple comorbidites	Negative	Anxiety, obese, obstructive sleepapnea	Diabetes mellitus, hypertension, heart failure, AF,aortic valve replacement, renal transplant on chemotherapy
Clinical presentation:FeverRespiratory symptomsGIT Symptoms	YesNoDiffuse abdominal pain and bleeding per rectum	YesCough, chest painNo	YesDry coughAcute abdomen	NoAcute respiratory failureNo
PI diagnosis:CT abdomen	PI in mid ascending colon	PI in caecum, RT colon with intraperitoneal free bubbles	PI in caecum, proximal ileum and Jejunum with mesenteric free air	PI in transverse and ascending colon
Additional CT abdomen findingPortal vein gas	Descending, sigmoid wall thickeningNo	NoNo	Bowel distensionYes	NoNo
D- dimer (ng/mL)	NA	Increasing from 1248 to 3398	NA	NA
Oxygen therapyManagement of PI	NABowel restHydrationIV antibiotics	YesCiprofloxacin plus metronidazole	Mechanically ventilatedUnfractionated heparin infusionVasopressorCrystalloid fluid	Mechanically ventilatedMetronidazole
Outcome	Complicated by sepsis, cardiac ischemia, renal insufficiency, and respiratory failure due to severe COVID 19	Improved	Improved	Improved
Explained mechanism of PI	- COVID19-induced ischemic colitis .	- Bowel wall damage and microbiota impairment due toSARS-COV-2 infection.Thromboembolicmechanism was excluded by doppler ultrasound on IVC, ileac, femoral, popliteal and infrapopliteal venous axis. Chest CT showed no pulmonary emboli	- SARS-COV-2 causes atrophy of the lymphoid follicles.That lead to increased mucosal permeability allowing dissection of the gas in the bowel wall.	- Multiple risk factors for PI is present with organ transplant.- Antibiotics therapy during ICU admission disrupted microbiota of the gut,- Direct damage of the bowel wall integrity by COVID-19 virus.

AF: atrial fibrillation, GIT: gastrointestinal tract, PI: pneumatosis intestinalis, CT: computed tomography, IVC: inferior vena cava, NA: not available.

Management of PI depends on the overall assessment of patients, considering medical and surgical history, clinical examination, laboratory assessment, and imaging are important in determining the treatment approach. Although PI management is generally conservative, surgery is indicated in complicated cases of perforation, peritonitis, abdominal sepsis, and failed conservative management [10].

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.