The post-COVID-19 intestinal damages: clinical, endoscopic and morphological features. The results of a single-center prospective observational cohort study

Abstract

Background: Clinical signs of gastrointestinal disorders can manifest both from the first days of COVID-19 and after recovery, and may last up to 6 months or more. Most studies examined the gastrointestinal changes in acute coronavirus infection, whereas intestinal abnormalities in the early and late post-COVID period and their causes have not been sufficiently studied. Aim: To determine the frequency and types of clinical, endoscopic and morphological abnormalities in patients with post-COVID-19 intestinal lesions. Materials and methods: This was a prospective, observational, open-label, cohort, non-controlled study in 72 patients with intestinal symptoms after the coronavirus infection (female 48, mean age 54.6 (95% confidence interval 51.08–58.12) years), who were admitted to the Department of Gastroenterology of general hospital during the first and second waves of COVID-19 from June 2020 to September 2021. The assessment included routine anamnestic, clinical, laboratory, endoscopic, and morphological methods. When indicated, visualization methods (ultrasound, computed tomography, magnetic resonance imaging) were performed. The treatment was symptom-oriented and aimed at inflammation, anemia and protein and electrolyte abnormalities. Outcomes were assessed by the time of discharge from the hospital and thereafter by telephone interviewing of the patients for 8 weeks. Results: In all patients, the main symptom was diarrhea, which started right just after SARS-CoV-2 infection with negative PCR test or 2–4 weeks later. The average stool frequency was 6.8 (5.61–7.99) times daily. In 19/72 patients (26.4%), there were blood and mucus in stools. 2.8% of the patients developed massive intestinal bleeding. Fever was present in 40.3% of the patients, decreased hemoglobin levels in 44.4%, and hypoalbuminemia in 16.7%. Signs of systemic inflammation (increased erythrocyte sedimentation rate, C-reactive protein, fibrinogen, thrombocytosis, leukocytosis) were found with various frequencies in a half of the patients. Clostridioides difficile A and B toxins were identified in 38.9% of the cases and increased fecal calprotectin in 22.2%. Ileocolonoscopy was performed in 67 patients. The colonic mucosa in 21 (31.3%) patients either was not different from the normal, or showed minimal inflammatory changes such as absence of vascular pattern, hyperemia, mild friability even in patients with severe diarrhea, fever and laboratory abnormalities. Pseudomembranous colitis was diagnosed in 12 (17.9%) patients, and focal hemorrhagic colitis in 11 (16.4%) patients. In 2 (3%) cases, moderate to severe ulcerative colitis was newly diagnosed after the SARS-CoV-2 infection. Single or multiple erosions and ulcers of various sizes against the unchanged surrounding mucosa were found in 19 (28.4%) patients. In 2 (3%) cases with profuse intestinal bleeding, the endoscopy showed diffuse spontaneous bleedings from colonic mucosa, with no local source of bleeding found. Biopsy samples from colonic mucosa were taken from 47 patients. Morphological abnormalities of only moderate or dense lymphoplasmocytic infiltration were detected in 29 (67.7%) patients, erosions in 8 (17%). In 2 (4.3%) cases, highly dense lymphoid infiltration with neutrophils, eosinophils and crypt abscesses was found, as typical for ulcerative colitis. In 2 (4.3%) patients, the lymphoid infiltration was associated with small venular and arteriolar clots, and in 5 (10.6%) patients there were no significant morphological abnormalities, except mild lymphoid infiltration. During the hospitalization period, 56.9% of the patients showed a decrease in stool frequency, improvement of clinical and laboratory signs of systemic inflammation and metabolic abnormalities, and partial restoration of their body weight. One patient with ulcerative colitis received adalimumab and achieved stable clinical and endoscopic remission. Complete recovery was noted in 27.8% of the cases within 4–8 weeks, among them in 1 patient who had had profuse intestinal bleedings. In 3 cases (4.2%), an emergency colectomy was performed due to severe pseudomembranous colitis. Two (2.8%) deaths were registered: one patient with newly diagnosed post-COVID severe ulcerative colitis died of pneumonia, and another patient died of severe multiorgan failure. In 6 (8.3%) cases, a moderate long-term (above 8 weeks) diarrhea with metabolic disorders, weight loss, but without systemic inflammationwas noted. Conclusion: In patients with post-COVID intestinal lesions, the clinical symptoms are almost the identical and manifest with diarrhea of varying severity, systemic inflammation and metabolic disorders, whereas the endoscopic and morphological lesions are quite diverse. The severity of clinical symptoms often does not correspond to poorly expressed endoscopic and morphological signs. The variability and inconsistency of the clinical, endoscopic and morphological changes have not yet been systematized and do not allow for a clearly formulated diagnosis (except cases of pseudomembranous and ulcerative colitis). This makes it impossible to provide pathophysiologically-based treatments.