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SARS-CoV-2 Infection in Children: Revisiting Host-Virus Interactions Through Post-Infection Immune Profiling
Catarina Gregório Martins1,2, Miguel Ângelo-Dias1,2, Maria de Jesus Chasqueira2,3
1Immunology, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 1169-056 Lisboa, Portugal.
Insights
Pediatric COVID-19 immune responses vary by age and severity. Younger children and severe cases show weaker antibody and cellular immunity, impacting management and vaccine strategies.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- COVID-19 in children often presents with milder symptoms but severe cases occur.
- Understanding age-related immune responses to SARS-CoV-2 is vital for pandemic preparedness.
- Immune dynamics in pediatric SARS-CoV-2 infection require detailed characterization across different time points.
Purpose of the Study:
- To characterize the dynamics of immune responses to SARS-CoV-2 in pediatric patients.
- To investigate age-, gender-, and disease severity-dependent variations in pediatric immune responses.
- To inform improved patient management and age-adjusted immunization strategies for COVID-19.
Main Methods:
- Analysis of 145 samples from 119 pediatric patients (<18 years) with confirmed SARS-CoV-2 infection.
- Assessment of immune markers at four distinct time points: <14 days, 14 days-3 months, 3-6 months, and 6-12 months post-infection.
- Characterization of T-cell activation, exhaustion (PD-1+), B-cell subsets (memory, antibody-secreting cells - ASCs), and antibody titers.
Main Results:
- Pediatric patients showed increased activated T-cells, exhaustion markers, ASCs, and decreased unswitched memory B-cells at infection.
- Both humoral and cellular anti-SARS-CoV-2 responses increased over time, with measurable responses in all patients at 6-12 months.
- Asymptomatic/mild cases had enhanced cellular responses and memory B-cells, while severe cases were younger, predominantly male, with altered T/B-cell ratios and reduced PHA responses.
- Younger children exhibited lower antibody titers and weaker cellular responses compared to adolescents, correlating with higher severe disease prevalence.
Conclusions:
- Immune responses to SARS-CoV-2 in children exhibit significant variations based on age, gender, and disease severity.
- Distinct immune profiles in asymptomatic/mild versus severe pediatric COVID-19 cases were identified.
- Findings support the need for tailored patient management and age-specific immunization strategies for pediatric COVID-19.
Abstract:
Children with COVID-19 typically experience milder symptoms and lower hospitalization rates, though severe cases do occur. Understanding age-related immune responses is crucial for future preparedness. We characterized immune response dynamics to SARS-CoV-2 in 145 samples from 119 pediatric patients (<18 years) with confirmed infection, assessed at four distinct time points: <14 days, 14 days-3 months, 3-6 months, and 6-12 months post-infection. At infection, patients presented increased activated T-cells, higher levels of exhaustion (i.e., PD-1+), lower numbers of unswitched memory B-cells, and increased antibody-secreting cells (ASCs). Both humoral and cellular anti-SARS-CoV-2 responses increased over time (all patients showed measurable responses in the last assessment). Asymptomatic/mildly symptomatic patients (58.6%) showed increased specific cellular responses from infection onwards, along with enriched memory B-cell subsets (but not ASCs), and distinct T-cell activation profiles. Children with severe disease were younger, predominantly boys, displayed altered T/B-cell ratios, and reduced PHA responses when infected. Compared to adolescents, younger children showed lower antibody titers and weaker cellular responses to SARS-CoV-2, possibly underlining the higher prevalence of severe manifestations in younger children. Our study illustrates important age-, gender-, and disease severity-dependent variations in immune responses to SARS-CoV-2, which can be helpful in improving patient management and immunization strategies adjusted to age groups.
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