Study explores differential immune responses against SARS-CoV-2 in adults and children

A recent study posted to the Research Square* preprint server, and currently under consideration at a Nature Portfolio Journal, revealed that the immune responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the clinical course of coronavirus disease 2019 (COVID-19) differed between children and adults.

SARS-CoV-2's spike (S), membrane (M), nucleocapsid (N) proteins, and viroporins (ORF7a and ORF3a), being potent immunogenic agents, trigger host immune cells resulting in robust antibody (Ab), B, and T lymphocyte responses. Usually, COVID-19 causes a mild or asymptomatic disease in the younger population (including children), and the lasting immunity against SARS-CoV-2 after recovery, is being actively researched.

According to some reports, the Ab responses to SARS-CoV-2 spike (S) and N proteins decrease progressively after six months post-infection. SARS-CoV-2-specific memory B lymphocytes form within two or three weeks of infection and remain in circulation for up to six months while CD4+ and CD8+ T lymphocyte responses wane over time. However, these studies are mostly limited to the adult and vulnerable groups, therefore, lacking information about children. It is essential to understand the long-term immunity to COVID-19 in children because they are not eligible for vaccinations across many regions.

The study

In the present study, a team of researchers explored the dynamics of immune responses in children. The authors examined families with at least one SARS-CoV-2-positive (confirmed with a polymerase chain reaction or PCR), adult or child, for about 12 months after infection. Participants were enrolled during the first wave of COVID-19 between May and July 2021, and specimens were collected at two timepoints – the first after four months since the onset of symptoms and the second after approximately a year.

Seropositivity was determined by testing for Abs against S1 (spike subunit), receptor-binding domain (RBD) of the S protein, and N protein. An individual was seropositive if any two of these Ab tests returned positive, and seronegative family members with no history of COVID-19 were included as negative controls.

Findings

The team investigated around 28 families, i.e., 61 adults and 50 children, with about 50 and 54% being seropositive, respectively. The COVID-19 disease was mild in all the infected individuals with asymptomatic presentations in 33.3% of children and 6.5% of adults.

The IgG and IgA Ab responses specific to S1, RBD, and N protein were determined. In children, the S1-specific Abs were higher than adults in samples collected at four months post-infection but, there was no such difference 12 months after infection. S1, RBD-, and N-specific IgG Abs declined over the observation period, with children losing N-specific IgG comparatively faster than adults. The researchers noted an increase in S1-specif IgA Abs exclusively in children.

Neutralizing Abs (NAbs) were present in both the cohorts but NAbs from children demonstrated greater neutralization potency than adults. Sera of individuals infected with wildtype SARS-CoV-2 effectively neutralized Alpha, Beta, and Gamma variants of concern (VOCs). Moreover, the neutralization breadth index (NBI), i.e., neutralization potency against the VOCs relative to WT virus, increased significantly with time.

In adults, plasmablasts and IgA2 positive B lymphocytes increased progressively over time, while switched memory B cells, plasmablasts, IgA2 positive B cells, and marginal zone-like B lymphocytes increased. The frequency of circulating S1-specific B cells was lower in children than adults at both timepoints. B lymphocytes showed progressive maturation in children as the S1- and RBD-specific B cells acquired CD27 marker late after infection.

T cell stimulation with SARS-CoV-2 peptides was performed in vitro to analyze activation markers CD137 and CD69. S1-reactive T lymphocytes were present in their sera at both time points in the two cohorts, although T cell frequency was higher in adults than children. CD4+ T cells were constant throughout the study in adults, but they significantly declined in children. CD8+ T cells remained in both cohorts over the observation period, but their frequency was lower in children.

Furthermore, T cells were stimulated with S1 and S2 peptides of four other coronaviruses, and the team observed comparable T cell activation in the two cohorts. CD4+ and CD8+ effector memory T cells remained largely uniform across adults at four- and 12-months post-infection; however, in children, CD4+ effector memory T cells decreased progressively. In contrast, CD8+ effector memory T cells increased progressively throughout the study. Humoral responses waned over time by 12-months post-infection while cellular immunity exhibited maturation as indicated by the expression of CD27 marker on B cells and memory phenotype in CD4+ and CD8+ T cells.

Conclusion

The study evaluated the differential immunity induced by SARS-CoV-2 infection in children and adults. It was characterized by dominant Ab and plasmablasts responses and lower numbers of specific memory B and T cells. Children had more robust serum antibody titers than adults, but RBD- or S1-specific memory B cells were less frequent.

Stimulation to different coronaviruses (pan-corona antigens) elicited similar responses in the two cohorts suggesting that reduced T cell responses in children could be specific to SARS-CoV-2 infection.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.