COVID-19 Infection in Children: Evaluating Humoral and Cellular Response

Mother taking care of sick daughter with oxygen mask and teddy bear
What humoral and cellular responses are exhibited by children post COVID-19 infection?

Children with SARS-CoV-2 infection demonstrate long-term persistence of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies, with IgG responses differing among children of differing ages. Moreover, most children do not exhibit cellular response 6 to 7 months after COVID-19 infection. These were among study findings published in Microbiological Research.

Much remains unknown about children’s humoral response to COVID-19 infection. Researchers therefore sought to examine humoral and cellular response to COVID-19 in children with COVID-19 infection.

The investigators conducted a longitudinal survey of 39 children (<18 years of age; mean age, 8.9±6.0 years; 23 females) with SARS-CoV-2 infection who were patients at Hospital Clínico San Carlos and Hospital Universitario de Getafe, both located in Madrid, Spain, between August 2020 and May 2021. Seroconversion rates were examined at 1 to 2 months after confirmed nonsevere SARS-CoV-2 infection; decreases in anti-RBD IgG antibody levels were analyzed at up to 7 months after the acute infection. The T-SPOT SARS-CoV-2 assay kit (Oxford Immunotec Ltd.) was used to diagnose the cellular immune response among the participants.

In terms of disease severity, 33 patients had asymptomatic/mild disease (5 were actually asymptomatic), and 6 had moderate disease. None of the children were diagnosed with severe or critical disease. In those participants with mild and moderate disease, the median duration of symptoms was 6 days (range, 3 to 10 days).

Researchers obtained 2 blood samples from each patient at different time points — 1 at the first visit, which was 1 to 2 months after the positive COVID-19 test, and the other at a second visit 6 to 7 months after the positive COVID-19 test.

Overall, 69.2% of the participants seroconverted. Although a significant decrease in antibody levels was reported over time (P <.01), no children seroconverted between the first and the second visits. In total, 37.5% of children under 6 years of age were seropositive, compared with 91.3% (21 of 23) of those older than 6 years of age (P <.01). 

The highest antibody levels were reported among seropositive younger children (P =.036). Overall, 33.3% of participants demonstrated a T-cell response. Among the participants who demonstrated a humoral response, no cellular response was detected in 51.9% of them.

Several limitations of the current analysis warrant mention. Because the study was longitudinal and included all children with confirmed COVID-19 infection, the sample size in the different groups is heterogeneous; arguably, said study authors, this is also a strength because it indicates that the study describes the antibody response of a real-world population of children. Another study limitation is that T-cell response was measured only at the second visit.

“Our findings show a long-term persistence of anti-RBD IgG antibodies in [pediatric] population and no seroreversion during the study period,” said study authors. “Our results suggest a different IgG response depending on the age, showing a low seroconversion rate among young children and a negative correlation between antibody levels and age,” they added, noting that further studies of COVID-19 infection in children are needed that show the effect of IgG antibodies in protective immunity.


Ruedas-López A, Berzosa-Sánchez A, Illán-Ramos M, et al. Longitudinal survey of humoral and cellular response to SARS-CoV-2 infection in children. Microbiol Res. Published online July 23, 2022. doi:10.1016/j.micres.2022.127145