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Distinct Immune Phenotypes and Cytokine Profiles in Children with Differing Severity of COVID-19
Laura Beatriz Talarico1,2, Analía Toledano1, María Marta Contrini3
1Department of Medicine, Laboratory of Infectious Diseases and Molecular Biology, Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, Argentina.
Insights
Pediatric COVID-19 immune responses vary by disease severity. Researchers identified distinct immune profiles in children with mild, severe, or multisystem inflammatory syndrome (MIS-C) related to SARS-CoV-2 infection.
Area of Science:
- Immunology
- Pediatrics
- Infectious Diseases
Background:
- Coronavirus disease 2019 (COVID-19) typically presents mildly in children.
- Severe outcomes include respiratory distress and multisystem inflammatory syndrome (MIS-C).
- Immune mechanisms driving these varied pediatric COVID-19 outcomes remain largely uncharacterized.
Purpose of the Study:
- To investigate the immune profiles associated with different clinical presentations of COVID-19 in children.
- To analyze laboratory parameters, antibody responses, immune phenotypes, and cytokine profiles in pediatric COVID-19 patients.
Main Methods:
- Prospective cohort study of 51 children with varying COVID-19 severity.
- Analysis of absolute lymphocyte counts, T cell subsets (CD3+, CD4+, CD8+), and HLA-DR expression.
- Measurement of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG levels and serum cytokine profiles (IL-1RA, TNF-α, RANTES, IL-1β).
Main Results:
- Lymphocyte and T cell counts (CD3+, CD4+, CD8+) decreased with increasing disease severity.
- SARS-CoV-2 IgG levels did not significantly differ across severity groups.
- Multisystem inflammatory syndrome in children (MIS-C) patients showed augmented exhausted effector memory CD8+ T cells and elevated IL-1β, with altered pro-inflammatory and anti-inflammatory cytokine profiles.
Conclusions:
- Distinct immune profiles correlate with disease severity in pediatric COVID-19.
- Findings highlight specific immune cell and cytokine alterations in severe COVID-19 and MIS-C.
- Further research in larger pediatric populations is needed to fully elucidate underlying immune mechanisms.
Background:
Coronavirus disease 2019 (COVID-19) is usually mild and self-limited in children. However, a few Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections in children may progress to severe disease with respiratory distress or can result in a multisystem inflammatory syndrome (MIS-C) associated with COVID-19. The immune mechanisms for these differential clinical outcomes are largely unknown.
Methods:
A prospective cohort study was performed to analyze the laboratory parameters, antibody response, immune phenotypes and cytokine profiles of 51 children with different clinical presentations of COVID-19.
Results:
We found that the absolute lymphocyte counts gradually decreased with disease severity. Furthermore, SARS-CoV-2 IgG levels in the acute phase and convalescence were not significantly different in patients with different disease severity. A decrease in CD3 + , CD4 + and CD8 + T cells was observed as disease severity increased. Both CD4 + and CD8 + T cells were activated in children with COVID-19, but no difference in the percentage of HLADR + -expressing cells was detected across the severity groups. In contrast, MIS-C patients exhibited augmented exhausted effector memory CD8 + T cells. Interestingly, the cytokine profile in sera of moderate/severe and MIS-C patients revealed an increase in anti-inflammatory IL-1RA and a suppression of tumor necrosis factor-α, RANTES, eotaxin and PDGF-BB. MIS-C patients also exhibited augmented IL-1β.
Conclusions:
We report distinct immune profiles dependent on severity in pediatric COVID-19 patients. Further investigation in a larger population will help unravel the immune mechanisms underlying pediatric COVID-19.
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