Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome

Abstract

Importance: Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown.

Objective: To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome.

Design, setting, and participants: A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged <18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase-polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases.

Main outcomes and measures: The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes.

Results: Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98-7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child's age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; >10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0).

Conclusions and relevance: In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications.

Figure 1.. Clinical and Biochemical Presentation of Children With Different Gastrointestinal Manifestations

Abbreviations: ESR, erythrocyte sedimentation rate; MIS-C, multisystem inflammatory syndrome in children.

Figure 2.. Factors Associated With Severe Gastrointestinal (GI) Outcomes in Multivariable Analysis

Adjusted odds ratios (aORs) and 95% CIs of factors associated with severe GI manifestations, adenomesenteritis, appendicitis, and fluid collection. Multivariable analysis included age, sex, GI symptoms, multisystem inflammatory syndrome in children (MIS-C), and variables found to have P ≤ .10 in the univariate analysis (eTable 1 in Supplement 1). Parameters necessary for the definition of MIS-C (ie, elevated leukocyte, C-reactive protein, and ferritin levels) were excluded from multivariable analysis to avoid biases. Red lines indicate significant findings; whiskers, 95% CIs.

Figure 3.. Imaging Findings in Children With Severe Gastrointestinal (GI) Involvement

A, Abdominal computed tomography (CT) images of a child (age, 4 years) affected by multisystem inflammatory syndrome in children (MIS-C) with subhepatic and diffuse mesenteric fluid collection (red arrowheads), mesenterial adenopathy, and fat inflammation (white arrowheads). B, Radiological localization of the most frequent GI manifestations. Fluid was collected from more than 1 site in some patients (ie, 34 sites in 21 patients). LLQ indicates left lower quadrant; LUQ, left upper quadrant; P, pelvis; RLQ, right lower quadrant; and RUQ, right upper quadrant.