Gastrointestinal Involvements in Children With COVID-related Multisystem Inflammatory Syndrome.

Dear Editors:

We read with interest the article by Miller et al reporting the gastrointestinal involvement in COVID-related multisystem inflammatory syndrome in children (MIS-C). Indeed, gastrointestinal symptoms are not uncommon in patients with Coronavirus Disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-Cov-2]) infection and may occur in the absence of any respiratory symptoms. As SARS-Cov-2 can also infect enterocytes through an angiotensin system by binding the angiotensin-converting enzyme 2 receptors, digestive symptoms might present in 50.5% of adult patients. Compared with adults, 13% of COVID-19–infected children are reported to have diarrhea, followed by nausea/vomiting (11%) and abdominal pain (6%). Besides the report of Miller et al, we have reviewed recent studies that describe pediatric patients diagnosed with Kawasaki-like MIS-C, who also presented with a variety of gastrointestinal symptoms and signs.3, 4, 5, 6, 7, 8 Strikingly, we found that 90% of 72 children with MIS-C, which was higher than the report of Miller et al., had gastrointestinal manifestations, most of which consisted of abdominal pain, vomiting, and diarrhea (Table 1 ). Besides, 10% of MIS-C cases had some rare presentations mimicking appendicitis and peritonitis, of which 3 cases were surgically explored. In contrast, only 2.3% to 4.6% of children with classic Kawasaki disease have been reported complicated with gastrointestinal involvement.

Table 1

Demographics and Clinical Characteristics of MIS-C Patients with Gastrointestinal Involvement

Case series	MIS-C cases, n	Age (median)/Gender, n	Incomplete KD, n (%)	GI involvements, n (%)	GI symptoms/signs, n (%)	Findings of GI system examination
Riphagen et al (2020)	8	8 y; male: 5	8 (100)	7 (88)	Diarrhea: 7 (88); vomiting: 4 (50); abdominal pain: 6 (75)	Not described in detail
Toubiana et al (2020)	21	7.9 y; male: 9	10 (48)	21 (100)	Abdominal pain with vomiting and diarrhea: 20 (95); acute surgical abdomen: 2 (10)	Abdominal ultrasound: peritoneal effusions in 4, 1 had abdominal surgery for suspected appendicitis with a final diagnosis of aseptic peritonitis
Belhadjer et al (2020)	35	10 y; male: 18	35 (100)	29 (83)	Abdominal pain, vomiting, or diarrhea present in 80	Exploratory laparoscopy in 2 cases due to suspected appendicitis, with a confirmed diagnosis of mesenteric lymphadenitis
Licciardi et al (2020)	2	9.5 y, male: 2	0	2 (100)	Abdominal pain and diarrhea: 2 (100), vomiting: 1 (50)	Abdominal ultrasound: both showed mesentery lymphadenitis or enlarged mesenteric lymph nodes
Waltuch et al (2020)	4	10 y, male: 3	3 (75)	4 (100)	Abdominal pain: 4 (100), diarrhea:	Abdominal ultrasound: mild ascites and inflammatory gallbladder in 1; abdominal CT: suspected appendicitis in 1
Dallan et al (2020)	2	10 y, male: 2	2 (100)	2 (100)	Abdominal pain: 2 (100); peritoneal signs: 2 (100); vomiting: 1 (50)	Abdominal CT: mesenteric lymphadenitis in 1

CT, computed tomography; GI, gastrointestinal; KD, Kawasaki disease; MIS-C, multisystem inflammation syndrome in children.

The high incidence of gastrointestinal involvement in MIS-C cases is unclear. The most plausible pathomechanism might be attributed to the overwhelming multiorgan inflammation, including the digestive system. This hypothesis might be further substantialized by the significantly high inflammatory markers and positive SARS-Cov-2 antibodies in the serum of most children, but negative viral reverse transcriptase polymerase chain reaction (RT-PCR) in nasopharyngeal swab or feces. Furthermore, the gastrointestinal investigations also showed mesenteric lymphadenitis and serous effusions (ascites) in severe cases, which implied that an active inflammatory reaction occurred in the digestive systems. However, a recent study on COVID-related gastrointestinal involvement showed that up to 41% of children without MIS-C had positive SARS-Cov-2 RT-PCR in feces. This finding may also reflect that the high incidence of gastrointestinal symptoms in MIS-C cases is likely due to the heightened inflammatory response.

Conclusively, our summary suggests that the gastrointestinal manifestations should not be overlooked in children with COVID-related MIS-C, and meticulous evaluation of the inflammatory response of the digestive system is essential to prevent unnecessary exploratory surgical intervention.