Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has had a drastic impact on our healthcare system, and providers are continuing to identify the spectrum of disease and symptoms across age groups. In the United States, children accounted for approximately 8% of all cases by the end of August.1 In children, COVID-19 presents as a wide spectrum of disease states, from asymptomatic infection to multi-system inflammatory syndrome.2,3 The data evaluating COVID-19 in infants are sparse, but appears to highlight most infants present with mild symptoms and require minimal supportive care unless the infant has significant comorbidities, such as congenital cardiac disease or prematurity.4,5 Our understanding of symptoms secondary to COVID-19 also continues to evolve. Coronaviruses have been implicated in pediatric acute gastroenteritis,6 and detection of SARS-CoV-2 RNA has been detected in stool samples of children recovering from COVID-19 pneumonia.7 Our case adds to the evolving COVID-19 literature as we report a unique case of a term male infant infected with COVID-19 who manifested clinical findings similar to necrotizing enterocolitis (NEC).
A 7-week-old male born at 37 weeks via vaginal delivery with medical history significant for neonatal jaundice requiring phototherapy initially presented to the emergency room (ER) with low-grade fever (100.4F), fussiness, poor oral intake, and mild congestion without respiratory distress. Vitals were stable, and labs were within normal limits. His clinical work-up was negative at that time, with the exception of a positive RT-PCR for SARS-CoV-2 from a nasopharyngeal swab. The infant was discharged from the ER after tolerating oral intake with no change in clinical status. Parents brought the infant back to the ER 2 days later with multiple episodes of emesis, large volume bloody stools, and lethargy. Despite being positive by RT-PCR for SARS-CoV-2, he had no notable respiratory symptoms. Vitals were significant for fever (101.1F) and tachycardia, with associated lab abnormalities including transaminitis (ALT 203/AST 403), elevated alkaline phosphate (636), elevated D-Dimer (1.09), elevated Ferritin (607) and persistently positive RT-PCR SARS-CoV-2. Significant normal lab values included white blood cell count 8.6, hemoglobin 10, platelets 405 and INR 1.0. On physical examination, the infant’s abdomen was distended and tender. Abdominal radiograph showed significant diffuse pneumatosis intestinalis (PI) with thickened intestine and no pneumoperitoneum (Fig. 1).
The infant was admitted to the intensive care isolation unit for resuscitation and close observation. Blood, urine, and stool cultures were collected at admission and subsequently negative. He was treated per the NEC protocol with antibiotics (piperacillin-tazobactam), bowel rest, gastric decompression, and serial imaging and abdominal examination by a pediatric surgeon. On hospital day 1, his abdominal examination was reassuring and surgery was not indicated. By hospital day 2, the bloody stools resolved, but he developed a significant lactic acidosis, which peaked at 6.3. On serial abdominal imaging, the pneumatosis remained significant and progressed to involve the entire colon. Given these worsening clinical and imaging findings, surgical exploration was considered, which would have likely required partial or total colectomy. Abdominal ultrasound showed simple perihepatic fluid and pneumatosis with peristalsing bowel, and the acidosis improved with fluid resuscitation. Since there was no evidence of colonic ischemic or perforation, surgery was deferred with continued serial abdominal examination and imaging. Antibiotic coverage was broadened to include anaerobic coverage with Metronidazole. On hospital day 3, the infant started to clinically improve. The NEC protocol was continued for 1 week. On serial abdominal radiographs, the colonic pneumatosis was resolved by day 5. Enteral nutrition was restarted on hospital day 9, which the infant tolerated well, and he was subsequently discharged on hospital day 10. Throughout hospitalization, inflammatory markers down trended, and he remained on room air without significant respiratory symptoms. At 2-week follow-up, the infant was asymptomatic with regular stooling and tolerating oral intake.
Our case describes an infant diagnosed with COVID-19 who presented with bloody stools and imaging significant for PI, similar to NEC. It is well known that the incidence of NEC increases with decreasing birth weight and gestational age, with only 15%–20% of cases occurring in term infants.8 Additionally, term infants with NEC typically have associated comorbidities such as congenital cardiac disease and are formula-fed. Case series regarding COVID-19 in neonates has primarily identified mild disease with severe disease limited to neonates and infants with associated comorbidities of prematurity or congenital cardiac disease.4,5 Interestingly, our patient was a term infant with no significant comorbidities or risk factors to develop NEC. A NEC epidemic in the early 1980s was thought to be secondary to Coronavirus after electron microscopy discovered Coronavirus viral morphology in neonatal stool samples and surgically resected specimens.9 During the current COVID-19 pandemic, no similar finding has been reported in the neonatal population to date. However, recent reports have identified adults presenting with bloody stools and associated gastroenteritis secondary to COVID-19.10
PI occurs when gas dissects into the bowel wall typically through intraluminal disruptions of the mucosa with the infiltration of gas-forming bacteria penetrating and further increasing air within the bowel wall. The most common reason for PI in an infant is secondary to NEC. NEC is characterized by ischemic necrosis of the intestinal mucosa with associated severe inflammation, invasion of enteric organisms, and dissection of gas along the bowel wall. The differential diagnosis for infant PI includes bacterial infectious enterocolitis, typhlitis, milk protein allergy and early onset inflammatory bowel disease. Stool cultures at admission were negative for Salmonella, Shigella and Campylobacter. Our patient also had no significant comorbidities of immunosuppression or immunocompromise, ruling out a possible diagnosis of typhlitis. Before admission, our patient was formula fed with a milk-based formula, Similac Sensitive. This raises the possibility of a milk protein allergy; however, the large volume bloody stools and extensive PI are unlikely to be solely secondary to a protein allergy. Additionally, Similac Sensitive was restarted before hospital discharge and the patient has not had a recurrence of symptoms. Early onset inflammatory bowel disease is highly unlikely in this age group with no significant family history. Therefore, given the worsening symptoms within 2 days of COVID-19 diagnosis, the PI and associated colitis was likely a manifestation of COVID-19.
Our patient was treated according to the NEC protocol and resolved with medical therapy alone. The tenets of medical therapy for NEC include (1) supportive care with resuscitation and bowel rest; (2) broad-spectrum antibiotics; and (3) serial abdominal examination, radiologic imaging, and laboratory analysis. Crystalloid resuscitation was performed upon admission and continued during the first 48–72 hours to correct lactic acidosis. Both bowel rest and broad-spectrum antibiotics were continued for a full week in our case. Serial abdominal examination and radiologic imaging were supportive of continued medical therapy, instead of surgical intervention, due to the lack of peritonitis and pneumoperitoneum. Interestingly, serial labs were not significant for classic lab abnormalities associated with NEC: anemia, thrombocytopenia, or evidence of disseminated intravascular coagulation.
A limitation of our report is our inability to collect stool samples or pathologic specimens to evaluate for the presence of SARS-CoV-2; however, the limited differential in a term infant with PI strongly suggests the findings are secondary to COVID-19. Fortunately, in this case, the colitis did not progress and cause perforation, but this could certainly occur in other similar cases. Early initiation of antibiotics covering bowel flora, bowel rest and resuscitation, similar to our tried and true medical management of NEC, should be considered for initial management to avoid surgical intervention.
1. Centers for Disease Control and Prevention. Demographic Trends of COVID-19 cases and deaths in the US reported to CDC. 2020. Available at: https://www.cdc.gov/covid-data-tracker/index.html
- demographics. Accessed July 24, 2020
2. Dufort EM, Koumans EH, Chow EJ, et al.; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem inflammatory syndrome in children in New York state. N Engl J Med. 2020; 383:347–358
3. Foster CE, Moulton EA, Munoz FM, et al. Coronavirus disease 2019 in children cared for at Texas children’s hospital: initial clinical characteristics and outcomes. J Pediatric Infect Dis Soc. 2020; 9:373–377
4. Kidszun A, Matheisl D, Tippmann S, et al. Effect of neonatal outcome estimates on decision-making preferences of mothers facing preterm birth: a Randomized Clinical Trial. JAMA Pediatr. 2020; 174:721–722
5. Wei M, Yuan J, Liu Y, et al. Novel coronavirus infection in hospitalized infants under 1 year of age in China. JAMA. 2020; 323:1313–1314
6. Xiong LJ, Zhou MY, He XQ, et al. The role of human coronavirus infection in pediatric acute gastroenteritis. Pediatr Infect Dis J. 2020; 39:645–649
7. Zhang T, Cui X, Zhao X, et al. Detectable SARS-CoV-2 viral RNA in feces of three children during recovery period of COVID-19 pneumonia. J Med Virol. 2020; 92:909–914
8. Velazco CS, Fullerton BS, Hong CR, et al. Morbidity and mortality among “big” babies who develop necrotizing enterocolitis: a prospective multicenter cohort analysis. J Pediatr Surg. 2018; 53:108–112
9. Rousset S, Moscovici O, Lebon P, et al. Intestinal lesions containing coronavirus-like particles in neonatal necrotizing enterocolitis: an ultrastructural analysis. Pediatrics. 1983; 73:218–224
10. Carvalho A, Alqusairi R, Adams A, et al. SARS-CoV-2 gastrointestinal infection causing hemorrhagic colitis: implications for detection and transmission of COVID-19 disease. Am J Gastroenterol. 2020; 115:942–946