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Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing
Maria Raffaella Petrara1, Francesco Bonfante2, Paola Costenaro3
1Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Insights
Children with COVID-19 show a more effective immune response than adults, with higher regulatory cells and neutralizing antibodies. This suggests a better long-term defense against SARS-CoV-2 in pediatric populations.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- The immune response is crucial for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes in adults but is understudied in children.
- Understanding age-related differences in pediatric COVID-19 immunity is essential for clinical management.
Purpose of the Study:
- To compare the immune profiles of adults and children infected with SARS-CoV-2.
- To investigate the relationship between immune cell activation, regulatory cells, and neutralizing antibody levels in different age groups.
Main Methods:
- Flow cytometry was used to analyze immune cell activation, senescence, exhaustion, and regulatory cells in 155 COVID-19 patients.
- Neutralizing antibody (nAb) levels were measured, and SARS-CoV-2 viral load was quantified in nasopharyngeal swabs.
- Immune profiles were compared between adult and pediatric COVID-19 patients at two time points post-infection.
Main Results:
- COVID-19 patients exhibited higher immune activation, exhaustion, and regulatory cells than non-COVID-19 subjects.
- Adults showed higher immune activation and senescence, inversely correlated with nAbs, compared to children.
- Children had higher regulatory T cells (Tregs) and regulatory B cells (Bregs), positively correlated with nAbs, and maintained these levels longer than adults.
Conclusions:
- Adults exhibit heightened immune activation and reduced neutralizing antibody production against SARS-CoV-2 compared to children.
- Viral load did not explain the observed age-related differences in immune response.
- Enhanced regulatory cell expression in children may facilitate reduced immune activation and a more robust specific immune response to SARS-CoV-2.
Background:
The immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population.
Methods:
Of 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1-3.7) and 6.1 (5.3-7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR).
Results:
Overall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes.
Conclusions:
Adults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.
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