COVID-19: focus on pediatrics and the immune response to
SARS-CoV-2
Significant morbidity and mortality secondary to COVID-19 infection have
largely spared the pediatric population, including pediatric hematology,
oncology and hematopoietic cell transplant patients.9In general, immunocompetent pediatric patients with COVID-19 experience
less severe disease than adult patients,10,11particularly adults with co-morbidities like cardiovascular disease,
chronic lung disease, and diabetes.12,13 Children
identified at higher risk for severe COVID-19, as defined by the need
for hospitalization or intensive care, include those with chronic
cardiovascular or lung diseases, infants under one year of age, and
immunocompromised patients receiving
immunosuppression.14
SARS-CoV-2 viral loads correlate with disease severity, as patients with
severe disease have higher viral loads and longer decay times than those
with mild or moderate symptoms.15 In contrast to viral
dynamics, the immune response to SARS-CoV-2 remains undefined, though
decreases in CD8+ T-cells and B cells in adults have
been correlated with severe COVID-19 and poor response to
therapy16 while CD8+ T-cells and B
cell recovery have been associated with moderate
disease.17 Decreases in regulatory T cells have also
been linked with a hyperinflammatory response in
adults,18 requiring the use of monoclonal blocking
antibodies like tocilizumab, an anti-interleukin 6 (IL-6)
agent.19 Interestingly, immune dysregulation and
hyperinflammation as measured by whole blood transcription profiles have
also been shown to correlate with severe respiratory syncytial virus
(RSV) disease in infants,20 who also have higher viral
loads and more protracted viral decay than infants with mild
RSV.21 Similarly, reports are emerging that some
children with COVID-19 are experiencing clinical symptoms and signs
consistent with Kawasaki Disease,22,23 a multi-system
inflammatory disease of unclear etiology but often associated with
respiratory viral infections.24
Despite their generally experiencing milder COVID-19, immunocompetent
pediatric patients have high viral loads25 and may
shed SARS-CoV-2 for weeks from the upper respiratory and lower
gastrointestinal tracts after primary infection.26This discrepancy between having milder COVID-19 despite having high
viral loads and prolonged viral shedding suggests that children may
differ from adults in their immune response to SARS-CoV-2. To this end,
children and adults have defined differences in both
innate27 and adaptive immune
responses28. As adults have a more pro-inflammatory
background, they may be predisposed to more severe COVID-19 via a
hyperinflammatory response to SARS-CoV-2.
Adults and children also differ in their immune response to viral
challenge29. Type I interferons (IFN) are key
cytokines that have direct viral cytotoxic effects30as well as immunomodulatory effects on both innate and adaptive immune
cells.31 Deficits in type I IFN have been correlated
with persistent viral load and exacerbated inflammatory response in
adult patients with severe COVID-19.32,33Interestingly, children with mild RSV disease (outpatient care) have
recently been shown to have higher viral loads, greater induction of IFN
genes and decreased gene expression of inflammation and neutrophils
versus children with severe RSV (inpatient care).34
Taken together, epidemiologic and immunologic data on SARS-CoV-2
infection are emerging that may be helpful to explore why pediatric
patients experience less severe COVID-19 and to implement potential
therapies that would either augment helpful or inhibit harmful immune
responses to SARS-CoV-2.35