Early immune responses and prognostic factors in children with COVID-19: a single-center retrospective analysis

Abstract

Background Early diagnostic indicators and the identification of possible progression to severe or critical COVID-19 in children are unknown. To investigate the immune characteristics of early SARS-CoV-2 infection in children and possible key prognostic factors for early identification of critical COVID-19, a retrospective study including 121 children with COVID-19 was conducted. Peripheral blood lymphocyte subset counts, T cell-derived cytokine concentrations, inflammatory factor concentrations, and routine blood counts were analyzed statistically at the initial presentation. Results The T lymphocyte subset and natural killer cell counts decreased with increasing disease severity. Group III (critical cases) had a higher Th/Tc ratio than groups I and II (common and severe cases); group I had a higher B cell count than groups II and III. IL-6, IL-10, IFN-γ, SAA, and procalcitonin levels increased with increasing disease severity. Hemoglobin concentration, and RBC and eosinophil counts decreased with increasing disease severity. Groups II and III had significantly lower lymphocyte counts than group I. T, Th, Tc, IL-6, IL-10, RBC, and hemoglobin had relatively high contribution and area under the curve values. Conclusions Decreased T, Th, Tc, RBC, hemoglobin and increased IL-6 and IL-10 in early SARS-CoV-2 infection in children are valuable indices for early diagnosis of severe disease. The significantly reduced Th and Tc cells and significantly increased IL-6, IL-10, ferritin, procalcitonin, and SAA at this stage in children with critical COVID-19 may be closely associated with the systemic cytokine storm caused by immune dysregulation.

A poor and delayed anti-SARS-CoV2 IgG response is associated to severe COVID-19 in children

“…Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in adults [ 31 , 32 ]. Consistent with previous reports [ 6 , [33] , [34] , [35] ], and contrasting with our observations made in children with mild or moderate COVID-19, we found that severe disease was associated to a systemic inflammatory profile, revealed by the presence of high concentrations of inflammatory cytokines in plasma. Some of these cytokines remained elevated in the convalescent phase of infection, as observed in adults with severe COVID-19 [ 19 , 36 ].…”

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis

“…We identified 9937 potentially relevant records from the literature databases and registers, and 1575 records from the additional searches. After screening the titles, abstracts and full texts, 56 studies (22 cohort studies, 9 case-control studies, and 25 case series) with a total of 79,104 patients were included [ [10] , [11] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] ] ( Fig. 1 ).…”

“…A total of 23 studies assessed risk factors for progression to severe or critical disease [ 25 , 26 , 28 , 30 , 33 , 36 , 42 , 49 , [51] , [52] , [53] , 55 , 59 , 60 , 61 , 63 , [65] , [66] , [67] , [68] , [69] , 71 , 76 ]. Neurological diseases ( OR =5.16, 95% CI 2.30 to 11.60, five studies, moderate-quality evidence) increased the odds of severe or critical disease.…”

Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention

“…Several genes have been identified for HLH (such as PRF1, UNC13D, STX11 and STXBP2) that encode molecules involved in the cytotoxicity of CD8-T cells and NK cells [94]. In this case, CD8-T cells and NK cells cannot lyse infected cells and this results in excessive immune stimulation (43). Another example is XIAP or NLRC4 deficiencies, which are associated with an overstimulation of the inflammasome [95].…”

“…However, similar or higher systemic levels of cytokine were observed in later studies of hospitalized children and adults [ 21 ]. On the other hand, high levels of inflammatory cytokines were observed in severe cases of pediatric COVID-19 [ 42 , 43 , 44 ] and also in children with mild disease [ 28 ]. A pivotal study by Pierce et al showed that children have a more intense nasal innate immune response, including higher levels of IFN-gamma and IFN-alpha, as compared to adults, suggesting that they may develop higher anti-viral responses at the mucosal level early on during infection [ 21 ].…”