Post-COVID-19 Intestinal and Mesenteric Mucormycosis

Abstract

A thirty-eight-year-old uncontrolled diabetic with a recent COVID-19 infection presented with extensive bowel ischemia and gangrene with a microscopic diagnosis of intestinal and mesenteric mucormycosis. Although there are a few reported cases of primary gastrointestinal mucormycosis, our case showing involvement of the intestine and/or mesentery, that too in a post-COVID patient, is quite uncommon. The immunosuppressive effect of the COVID-19 disease, uncontrolled diabetes, and the use of corticosteroids for the treatment of severe COVID are the most probable reasons for the emergence of severe opportunistic infections, both as a coinfection and as a sequalae to COVID.

Brief Report

India has just witnessed the second wave of the coronavirus disease 2019 (COVID-19) pandemic. As the disease process is evolving and as we are testing newer therapeutic strategies, the burden of complications too is increasing. These complications are either disease related, patient related (e.g., comorbidities like diabetes), or management related (e.g., corticosteroid therapy and ventilation). All these factors have together contributed to the recent increase in the incidence of severe opportunistic infections in COVID-19 or COVID-recovered patients. ¹ One such pathogen that has risen in alarming proportions in India is mucormycosis, so much so that several states had declared it an epidemic. However, majority of the cases of post COVID mucormycosis reported so far have been in the rhino-orbito-cerebral regions. ¹ We report an uncommon case of intestinal and mesenteric mucormycosis in a post-COVID patient.

A thirty-eight-year-old woman, a known case of type 2 diabetes for the last 7 years, on irregular medication, presented to the emergency department with complaints of diffuse abdominal pain more on the right side for 6 days which was associated with nausea and vomiting. 14 days back, she had tested positive for COVID-19 with symptoms of fever and cough. She had been symptomatically managed at a local hospital with antipyretics, ivermectin, and oral hypoglycemic drugs. There she had also undergone a CT (computed tomography) scan of the thorax showing patchy areas of peripheral predominant ground-glass opacities and consolidation in bilateral lungs. The CT severity of lung involvement was assessed using the scoring system proposed by Chang et al, which amounted to 14/25. Owing to her mild symptoms, she was not prescribed any anticoagulants. As per the hospital records, her D-Dimer was .52 mcg/ml, Interleukin-6 levels was 4.6 pg/mL and blood sugars were in the range of 300-400 gm/dl.

On arrival to our center, she was on room air with a saturation of 99% and her RT-PCR test for COVID-19 came negative. She had tenderness and guarding over the right iliac fossa on local abdominal examination. She was also found to be in diabetic ketoacidosis and had raised leukocyte counts, the management of which was promptly started and a CECT (contrast-enhanced computed tomography) abdomen was done. Pneumoperitoneum with thrombosis of the ileocolic artery causing gangrene of the cecum, ascending colon, and part of the transverse colon was reported along with a right kidney infarct. (Figure 1)

Figure 1.

Multiplanar reformatted contrast-enhanced CT images of a 38-year-old female. (A) Computed tomography in lung window shows changes of previous COVID-19 infection with patchy areas of peripheral predominant ground-glass opacities in bilateral lung fields. (B) Axial (C) coronal images show dehiscent papery thin non-enhancing medial wall of cecum and ascending colon with air foci and fat stranding within the mesentery (red arrow) suggestive of gangrenous changes, thrombosis of ileocolic branch of superior mesenteric artery, hypo-enhancement of adjacent D2 and D3 segment of duodenum (white arrow), and rectosigmoid colon (yellow arrow). (D) Sagittal image shows an infarct in the inferior pole of right kidney (blue arrow).

After the initial resuscitation in the intensive care unit (ICU), she was taken up for an exploratory laparotomy. The terminal ileum, cecum, ascending colon, and nearly half of transverse colon were gangrenous and were resected. (Figure 2) In view of intraoperative instability, inotropes and vasopressors were started. A damage control approach with the formation of barrel stoma and a mesh laparostomy was done, and the patient was quickly shifted back to the ICU.

Figure 2.

Intraoperative image showing (A) gangrenous distal ileum (red arrow) ascending colon (yellow arrow) and mesenteric thickening and discoloration (black arrow) and (B) gangrenous cecum with greyish patches (blue arrow).

Postoperatively, she was started on liposomal amphotericin B (200 mg IV) along with broad spectrum antibiotics. The requirement for her inotropes and vasopressor drugs kept on increasing till she went into refractory shock and multiorgan dysfunction syndrome. Even with early surgical resection and early administration of antifungals, she succumbed to her disease on the third postoperative day. Informed consent was taken from the next of kin regarding publication of her case in medical literature.

The resected specimen revealed patchy lesions on the intestinal wall along with a thickened mesentery. The intestinal and mesenteric tissue sent for a KOH mound-reported presence of broad hyaline aseptate and right-angled branched fungal suggestive of mucormycosis.

Mucormycosis generally encompasses infections due to fungi of the order mucorales. It is a surgical emergency, in which urgent intervention is recommended even if there is a slight suspicion on clinical or radiological grounds. ² This is due to the rapidly progressive and destructive nature of the disease, with an overall mortality rate of 40%-80% depending on the site of infection and the general condition of the patient. ² The most common route of infection is by inhalation of spores causing pulmonary involvement and rhino-orbito-cerebral disease (typically in diabetics). ² Primary gastrointestinal mucormycosis occurs in neonates, with a very high mortality. ² However, it is extremely rare in adults (>18 years age), and we came across very few articles related to it. Stomach seems to be the most common site of gastrointestinal involvement.

Opportunistic infections are increasingly being reported in COVID-19 patients. Though still debatable, there are some possible explanations to the association between COVID-19 disease and mucormycosis in our patient. First, extensive lung damage has been reported following COVID-19 infection, which may serve as a focus for opportunistic fungal infection. Second, immune system dysregulation (reduced CD4⁺ and CD8⁺ lymphocytes) may contribute to COVID-19-related immunosuppression. Third, severe COVID-19 management involves mechanical ventilation, prolonged intensive care, and the use of corticosteroids which can act as a double-edged sword promoting opportunistic infections. ²

Two cases with similar pathology have been reported from India till now, ours being the third.^3,4 Our patient was an uncontrolled diabetic with a history of COVID-19 infection in the past 2 weeks. She, however, had only mild COVID-19 symptoms, and no history of administration of immunosuppressive drug nor an anticoagulant. Pre-operative diagnosis of mucormycosis and ischemia of the bowel and mesentery is challenging for both the surgeon and the radiologist as this an uncommon entity with nonspecific signs and symptoms. Early diagnosis, prompt surgical resection, early administration of liposomal amphotericin B/posaconazole, and sound critical care management are the key factors that help in reducing the mortality in such cases. ² The management of such cases should be undertaken by a multidisciplinary team, as was done in our case.

With the pandemic continuing relentlessly and with the newer therapeutic options, clinicians must be aware of the risks of opportunistic infections.

Gastrointestinal mucormycosis is rare, and even with aggressive treatment, the mortality remains high. Clinicians, therefore, should consider gastrointestinal mucormycosis as a differential for acute abdomen in post-COVID patients, especially if the patient is diabetic and/or has been on corticosteroids.