In January 2020, a novel coronavirus, SARS-CoV-2, was described in Wuhan, China. This virus produces coronavirus disease 2019 (COVID-19), and its rapid spread has led to the declaration of a global health emergency and pandemic by the World Health Organization.1,2 Spain has been one of the more severely affected countries in the world by this pandemic, and Madrid, its capital, has seen the highest rate of infection and mortality in the country.3,4
In previous epidemics caused by coronaviruses, scant data on pediatric patients have been published, and the impact of COVID-19 seems to be lesser among the pediatric population.5,6 This lack of data is more pronounced in children requiring pediatric intensive care unit (PICU) admission.7 Recently, a hyperinflammatory syndrome with multiorgan involvement in children related to SARS-CoV-2 infection has been reported.8,9
To optimize the provision of health care to adults with COVID-19, the Madrid health authority decided to centralize pediatric care.4 Under this initiative, children with SARS-CoV-2 infection were transferred to only 2 tertiary hospitals. In this brief report, we describe the epidemiologic features, clinical manifestations and disease course in 5 children admitted for PICU care in 1 of these hospitals. All were admitted due to suspected acute abdomen or abdominal sepsis. This clinical presentation has not been previously described in children with SARS-CoV-2 infection.
Case 1: SARS-CoV-2 Infection Confirmed by Polymerase Chain Reaction
A 12-year-old male presented to the emergency department (ED). Five-day history of vomiting, diarrhea and abdominal pain, mostly in the right iliac fossa. He presented with hypoperfusion, hypotension and tachycardia. The patient developed skin lesions 2 days before presenting to the ED (Fig. 1A). Findings from abdominal ultrasound and abdominal computed tomography (CT) showed signs of ileitis and colitis. An initial SARS-CoV-2 polymerase chain reaction (PCR) from nasopharyngeal swab was negative. The child was admitted to the PICU with suspected abdominal sepsis and hemodynamic instability. A chest radiograph revealed no abnormalities (Fig. 1B). Inotropic medication (norepinephrine and adrenaline) and respiratory support [high-flow oxygen nasal cannula (HFNC)] were initiated on admission in addition to meropenem and amikacin. At 10 hours of admission, the patient increased respiratory work and needed higher fraction of inspired oxygen (FiO2). A chest radiograph showed evidence of bilateral pneumonia (Fig. 1B). He then required orotracheal intubation and mechanical ventilation. A Sars-CoV-2 PCR test on bronchial washing was positive. The therapies used are described in Table 1. Two doses of tocilizumab were administered. The patient evolved favorably. Inotropic support was withdrawn on the sixth day of admission and the patient was extubated on the seventh day. Blood and stool cultures were negative for bacteria. A progressive decrease was observed in classical inflammatory biomarkers. Antimicrobial therapy was discontinued before PICU discharge (13 days of admission).
Case 2: SARS-CoV-2 Infection Confirmed by Serology
A 9-year-old male presented to the ED with a 5-day history of abdominal pain in the right iliac fossa. He had presented fever over the last 3 days and reported vomiting without diarrhea. He was dehydrated. Following this, an abdominal ultrasound revealed intestinal inflammation. He was admitted to the pediatric ward and treated with cefotaxime due to a suspected bacterial infection. Testing for SARS-CoV-2 infection from nasal swab sample was negative. On the second day of admission, he presented hypotension (70/40 mm Hg) and tachycardia. He required volume expansion. He was transferred to the PICU due to hemodynamic instability. Inotropic support with norepinephrine was initiated and maintained for 24 hours. While in the PICU, the patient complained of diffuse abdominal pain. Suspecting sepsis of abdominal origin, the attending physician replaced cefotaxime with piperacillin–tazobactam. Empirical treatment for SARS-CoV-2 infection was started. Blood tests, biomarkers and therapies are shown in Table 1. Before PICU discharge, serologic testing was positive for IgG SARS-CoV-2 (IgM SARS-CoV-2 was negative). The patient was discharged from PICU after 6 days.
Case 3: SARS-CoV-2 Infection Confirmed by PCR
A 9-year-old female presented to ED with abdominal pain and a 3-day history of fever in addition to vomiting and diarrhea. On examination, she was hemodynamically stable but showed signs of dehydration. Elevation of acute phase reactants was observed on blood testing; as a result, treatment with intravenous cefotaxime was initiated, and a COVID-19 PCR was performed on nasal swab samples, with positive results. The patient was transferred to the pediatric ward. Twenty-four hours after admission, she presented clinical deterioration with tachycardia and hypotension. After volume expansion with crystalloids, she was admitted to the PICU. Inotropic support with norepinephrine was administered. An abdominal ultrasound scan was performed, revealing signs of intestinal inflammation. She received respiratory support with HFNC for tachypnea, and a right pulmonary infiltrate was visible on the chest radiograph. Results of blood testing and the therapies appear in Table 1. A single dose of tocilizumab was administered. The patient responded favorably, allowing withdrawal of inotropic support after 24 hours. She was discharged after 2 days of PICU admission.
Case 4: SARS-CoV-2 Infection Confirmed by Cerology
A 10-year-old male presented to the ED with a 4-day history of abdominal pain, particularly in the right iliac fossa. He had a fever of up to 39°C and reported vomiting and diarrhea 24 hours before ED presentation. The physical examination was compatible with acute abdomen. He showed skin lesions (Fig. 2). An abdominal ultrasound and abdominal CT scan were performed, ruling out surgically treatable disease. Results of blood testing are provided in Table 1. The patient developed tachycardia and hypotension. Due to suspected hemodynamic instability and abdominal sepsis, he was admitted to the PICU. SARS-CoV-2 PCR testing with a nasal swab was negative. He received volume expansion, and she did not require inotropic support. He was treated with meropenem. Despite the negative PCR results for SARS-CoV-2 empirical treatment was started. Prophylactic heparinization was also performed. Later he evidenced increased respiratory work, bilateral basal hypoventilation and left pulmonary crackles. He required HFNC for 24 hours. Serologic testing was positive for SARS-CoV-2 IgG antibodies. He was discharged from the PICU after 5 days.
Case 5: Suspected SARS-CoV-2 Infection
A 13-year-old male presented to the ED with a 48-hour history of abdominal pain and vomiting. In the hours before reporting to the ED, he developed fever with chills and had poor perfusion and acrocyanosis. In the ED, tachycardia and hypotension were observed. Volume expansion was performed with saline. Acute abdomen was suspected on physical examination. Presence of surgically treatable disease was ruled out. Results of blood test and image test are given in Table 1. He was admitted to the PICU due to hemodynamic instability and suspected abdominal sepsis. Antibiotic therapy with meropenem and amikacin was initiated. He required repeated volume expansions. Inotropic support with norepinephrine and epinephrine was maintained for 2 days. SARS-CoV-2 PCR testing using a nasal swab was negative. A chest radiograph showed no alterations, and he presented no respiratory symptoms. The patient received empirical treatment for SARS-CoV-2 infection. One dose of tocilizumab was administered. No microbiologic confirmation of bacterial infection was obtained from the collected cultures. He was discharged after 3 days of PICU admission.
The clinical expression of SARS-CoV-2 infection in children is not fully known. In this brief report, we describe 5 consecutive cases of suspected acute abdomen caused by this novel pathogen. No publications of the disease manifestation have appeared in the literature but our observations are quite similar from the recently communicated by Riphagen et al.8 Not all patients presented active infectious disease, and the presence of skin lesions was an interesting sign. Furthermore, respiratory symptoms were not prevalent on PICU or hospital admission.
Inotropic support was required in almost all cases,10 and one needed mechanical ventilation.11 What we observed is compatible with a multisystem inflammatory state with affection of different body functions. In our cases, this could lead to leaky blood vessels and low blood pressure.9 Only one patient presented respiratory symptoms on admission. All patients had moderate to severe dehydration. Presence of lymphopenia, elevated ferritin, d-dimer and interleukin-6 was a common finding of laboratory tests.12–14 All patients received empirical SARS-CoV-2 treatment.13,15,16
In summary, we describe a severe presentation of SARS-CoV-2 infection in children, which has not been completely described previously, requires close monitoring and advanced supportive treatment. This presentation is not always associated with active infection.8,12,17 The presence of abdominal pain and skin manifestations may lead to suspicion. By registering and reporting cases like these for the global community, a standard of care and appropriate etiologic diagnosis may be established.
1. Khan S, Siddique R, Shereen MA, et al.Emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2: biology and therapeutic options. J Clin Microbiol. 2020;58:e00187–e00120.
2. Peeri NC, Shrestha N, Rahman MS, et al.The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Int J Epidemiol. 2020;pii:dyaa033.
3. España MdSdSituación de COVID-19 en España, Ministerio de Sanidad. 2020. Available at: https://covid19.isciii.es
. Accessed April 30, 2020.
4. Tagarro A, Epalza C, Santos M, et al.Screening and severity of coronavirus disease 2019 (COVID-19) in children in Madrid, Spain. JAMA pediatrics. 2020.
5. García-Salido AThree hypotheses about children COVID19. Pediatric Infectious Disease J. 2020;Online First.
6. García-Salido ARevisión narrativa sobre la respuesta inmunitaria frente a coronavirus: descripción general, aplicabilidad para SARS-CoV-2 E implicaciones terapéuticas. Anales de Pediatría. 2020. Epub ahead of print.
7. Zimmermann P, Curtis NCoronavirus infections in children including COVID-19: an overview of the epidemiology, clinical features, diagnosis, treatment and prevention options in children. Pediatr Infect Dis J. 2020;39:355–368.
8. Riphagen S, Gomez X, Gonzalez-Martinez C, et al.Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;pii: S0140-6736(20)31094-1.
9. Mahase ECovid-19: concerns grow over inflammatory syndrome emerging in children. BMJ. 2020;369:m1710.
10. Chen C, Zhou Y, Wang DWSARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020;45:230–232.
11. Cunningham AC, Goh HP, Koh DTreatment of COVID-19: old tricks for new challenges. Crit Care. 2020;24:91.
12. Prompetchara E, Ketloy C, Palaga TImmune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38:1–9.
13. Qin C, Zhou L, Hu Z, et al.Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;pii: ciaa248.
14. Zhou F, Yu T, Du R, et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.
15. Guan WJ, Ni ZY, Hu Y, et al.Clinical characteristics of coronavirus disease 2019 in China. New England J Med. 2020.
16. Shang L, Zhao J, Hu Y, et al.On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020;395:683–684.
17. Li G, Fan Y, Lai Y, et al.Coronavirus infections and immune responses. J Med Virol. 2020;92:424–432.