A retrospective single-center case series of 50 hospitalized pediatric COVID-19 patients in New York City found that respiratory symptoms were common but not ubiquitous, that most children had underlying illnesses, and that obese patients were likely to require mechanical ventilation.
A separate single-center case series published today in JAMA Network Open found that that pediatric COVID-19 patients with moderate disease had higher levels of the inflammatory marker interleukin 10 and lower levels of neutrophil immune cells than those with mild illness, suggesting that the virus may be associated with abnormal immune responses.
Obesity, inflammation, mechanical ventilation
The first study, published today in JAMA Pediatrics, involved patients 21 years or younger at New York-Presbyterian Morgan Stanley Children's Hospital from Mar 1 to Apr 15.
It showed that infants and immunocompromised patients were no more likely to become seriously ill than their peers — but that signs of inflammation were linked to severe disease.
Twenty-seven of 50 patients (54%) were boys, and 25 (50%) were Hispanic; the authors noted that their hospital serves mostly Hispanic patients. Median time from symptom onset to hospitalization was 2 days. Forty-nine (98%) had been infected in the community, while 1 (2%) was thought to be infected in a healthcare setting.
Forty patients (80%) had fever, while 32 (64%) had respiratory symptoms, and 3 (6%) had only gastrointestinal symptoms. Lymphopenia (a reduced count of a type of white blood cells important in immunity) occurred in 36 patients (72%) but was not significantly different between those with or without serious illness.
The most common underlying condition was obesity, in 11 of 50 patients (22%). Another eight patients (16%) were overweight. Six of nine obese patients 2 years or older (67%) required mechanical ventilation, versus 5 of 25 children (20%) of healthy weight.
Sixteen patients (32%) needed respiratory support, including 9 (18%) who received mechanical ventilation. One patient (2%) died. None of the 14 infants were seriously ill, while one of eight immunocompromised patients became severely ill.
Severe disease was linked to significantly higher levels of the inflammatory markers C-reactive protein and procalcitonin at admission, while the inflammatory markers interleukin 6, ferritin, and D-dimer levels were elevated during hospitalization in these patients.
The authors said that while their data confirm previous findings that children with COVID-19 are less likely than adults to require hospitalization, kids are still vulnerable to severe disease and may have atypical presentations.
"Expanded testing, maintaining a high suspicion for severe acute respiratory syndrome coronavirus 2 infection given the variable presentation of COVID-19, risk stratification, and recognition of findings suggestive of immune dysregulation are crucial to effective COVID-19 management in children," they concluded.
In a commentary in the same journal, Jason Newland, MD, MEd, of Washington University School of Medicine in St. Louis and Kristina Bryant, MD, of the University of Louisville in Kentucky said that more research is needed on the multisystem inflammatory syndrome linked to COVID-19 and the causes of racial disparities in infections and outcomes.
"Multicenter collaborative studies are needed to define the infectious and postinfectious sequelae of COVID-19 in children in communities across the US, including rural communities, and in all racial and ethnic groups," they wrote. "We also need to understand the association of the pandemic with adverse health outcomes in children beyond the consequences of viral infection."
Dysregulated immune responses
The second retrospective study involved 157 COVID-19 patients 1.5 to 10 years old in Wuhan Children's Hospital in China from Jan 25 to Apr 18. Eighty-eight patients (59.5%) were girls, and children with moderate illness were significantly younger than those with mild illness (median age, 5.5 months vs 9 months).
Sixty patients (38.2%) had mild illness with pneumonia, 88 (56.1%) were moderately ill, 6 (3.8%) had severe disease, and 3 (1.9%) were critically ill, two of whom also had leukemia and died.
Abnormal lab findings included elevated levels of alanine aminotransferase, aspartate aminotransferase, creatine kinase MB (CK-MB) activity, and lactate dehydrogenase, indicating liver and heart damage.
Patients with moderate illness had elevated levels of the inflammatory marker interleukin 10 and decreased neutrophil levels. Elevated lymphocytes, CD4+ T immune cells, and interleukin 10 were positively associated with liver and heart damage. Systemic inflammation, as indicated by elevated cytokine levels, was rare.
The authors noted that elevated neutrophil-to-lymphocyte ratios (indicating inflammation) were not seen in the pediatric patients, in contrast with findings from adult data, suggesting that age-related neutrophil recruitment may explain why COVID-19 causes milder illness in children.
And while adults with moderate or severe illness had decreased levels of CD4+ T cells, which calm inflammation, this was not the case in the pediatric patients, in whom only 3 (1.9%) had decreased levels. In fact, 14 pediatric patients with moderate illness (15.9%) had increased levels. Meanwhile, B cells and antibodies were significantly decreased in pediatric patients with moderate illness.
"Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of severe acute respiratory syndrome coronavirus 2 [the virus that causes COVID-19] infection could be important for the clinical management of COVID-19," the authors wrote.