Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults

Abstract

BackgroundThe 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.MethodsOf 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).ResultsOverall, 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.ConclusionsAdults 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.

Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months

“…Here, we describe the kinetics, function, and phenotype of SARS-CoV-2-specific T cells of infected children in comparison with adults experiencing mild to moderate COVID-19 symptoms. Only limited studies have been reported investigating the immune responses in children with mild/asymptomatic SARS-CoV-2 infection (17)(18)(19)(20)(21). The strength of our study is that we evaluated the recall T cell response upon SARS-CoV-2 specific stimulation, and compared it to unexposed children and adults.…”

“…Nevertheless, it remains unclear whether SARS-CoV-2 infection in children, usually showing a mild course, induces substantial T cell immunity. Only a few reports describe the immune responses in children with mild disease or asymptomatic infection, although in these studies T cells specifically reactive to SARS-CoV-2 were not investigated (17)(18)(19)(20). Recently, a study was published investigating SARS-CoV-2 specific T cell responses in children (21).…”

COVID-19 in children: From afterthought to unknown

“…In line with this hypothesis, a better regulatory activity associated with lower immune activation status has been reported in asymptomatic COVID children ( Figure 1 C). 8 …”

“…A number of recent studies have clarified that the COVID-19 clinical burden in children is mostly due to over-inflammation and immune cells dysregulation. 8 , 9 It must be noted that an apparently similar hyperinflammation status that characterizes severely ill COVID-19 adults could also be present in children. Critically ill children present with a pro-inflammatory syndrome characterized by a phenotypic picture resembling Kawasaki disease (KD) or toxic shock syndrome possibly related to COVID-19.…”

The COVID-19 pandemic in children and young people during 2020-2021: Learning about clinical presentation, patterns of spread, viral load, diagnosis and treatment

“…In adults, higher immune activation persisted after 6 months of infection, while children maintained high levels of regulatory cells. The studies showed that adults displayed higher immune activation and lower production of anti-SARS-CoV-2 neutralizing antibodies than children, and this difference in immune response was not related to different viral loads [ 83 ]. Laboratory analyses based on saliva samples demonstrated the heterogeneity of the SARS-CoV-2 antibody response in children and showed the additional value of saliva antibody detection [ 84 ].…”