Mild Cytokine Elevation, Moderate CD4+ T Cell Response and Abundant Antibody Production in Children with COVID-19

Abstract

Children with Coronavirus Disease 2019 (COVID-19) were reported to show milder symptoms and better prognosis than their adult counterparts, but the difference of immune response against SARS-CoV-2 between children and adults hasn't been reported. Therefore we initiated this study to figure out the features of immune response in children with COVID-19. Sera and whole blood cells from 19 children with COVID-19 during different phases after disease onset were collected. The cytokine concentrations, SARS-CoV-2 S-RBD or N-specific antibodies and T cell immune responses were detected respectively. In children with COVID-19, only 3 of 12 cytokines were increased in acute sera, including interferon (IFN)-cinduced protein 10 (IP10), interleukin (IL)-10 and IL-16. We observed an increase in T helper (Th)-2 cells and a suppression in regulatory T cells (Treg) in patients during acute phase, but no significant response was found in the IFN-cproducing or tumor necrosis factor (TNF)-a-producing CD8 ? T cells in patients. S-RBD and N IgM showed an early induction, while S-RBD and N IgG were prominently induced later in convalescent phase. Potent S-RBD IgA response was observed but N IgA seemed to be inconspicuous. Children with COVID-19 displayed an immunophenotype that is less inflammatory than adults, including unremarkable cytokine elevation, moderate CD4 ? T cell response and inactive CD8 ? T cell response, but their humoral immunity against SARS-CoV-2 were as strong as adults. Our finding presented immunological characteristics of children with COVID-19 and might give some clues as to why children develop less severe disease than adults.

Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients

“…A role for Th2 cell-type responses in severe COVID-19 is still unclear ( 48 ). An increased Th2 response was described as beneficial in children with COVID-19, due to its potential to reduce exaggerated inflammation ( 49 ). However, we observed that severe COVID-19 patients display strongly up-regulated IL-4 production in both CD4 + and CD8 + T cells.…”

The role of CD4+FoxP3+ regulatory T cells in the immunopathogenesis of COVID-19: implications for treatment

“…Interestingly, a report shows that the frequency of Tregs (CD3 + CD4 + CD25 hi CD127 lo ) was significantly declined in critically ill patients, while that was increased in mild and severe cases after SARS-CoV-2 infection [51]. Other studies also found that the proportion of Tregs in CD4 T was reduced in adults and children with severe COVID-19 [11,64,65]. These studies conclude that a reduced number of Tregs, as well as increased Th17 responses, may be attributable to the excessive inflammation and pathogenesis of COVID-19.…”

A Mechanistic Link Between Selenium and Coronavirus Disease 2019 (COVID-19)

“…Children have a lesser expression of ACE2 receptor in the lungs than adults, and therefore virus has less chance to invade their lungs [35]. Once infected, children develop less intense immunopathological reactions which are probably due to an immature immune system not trained to cause hyperinflammation, and therefore, there is a less chance of developing ARDS [37]. Other supporting factors include better repair power (of damaged respiratory tissues), and low occurrence of comorbid conditions.…”