COVID-19 Antibody Levels Rise Higher, Fall Faster in Children

Given the high transmissibility and potential lethality of SARS-CoV-2, vaccination remains a potent strategy to fight morbidity and mortality–yet the question of how and when to vaccinate children, especially young children, has been hotly debated. To gain an understanding of the mechanisms of childrens’ immune response to COVID-19, an Italian team of scientists conducted a study examining antibody titer levels in children after infection and comparing them with antibody levels in adults. The study was published in July in JAMA Network Open.

The subjects were part of family groups enrolled at the COVID-19 Family Cluster Follow-up Clinic in the Department of Women’s and Children’s Health in Padua between April 1, 2020 and August 31, 2021. After excluding people who had received at least 1 dose of COVID-19 or who were found to not have COVID-19, the team ended up with 659 individuals (parents and children) representing 252 family clusters, all of whom had at least 1 measure of anti-receptor-binding domain (RBD) IgG titers taken after infection. Because RBD antibodies are strongly correlated with neutralizing antibodies (NAbs), measuring their levels is an effective method of determining the strength of an individual’s COVID-19 immune response.

The team analyzed titer samples collected 1 to 4 months, 5 to 9 months, and 10 months or more after COVID-19 infection. Within each of those time frames, subjects were stratified into groups including younger than age 3, 3 to 5, 6 to 11, 12 to 17, and 18 or older. In each of the 3 time frames studied, younger children displayed measurably higher antibody levels than older ones–up to 5-fold higher in the under-3s compared with the 18-and-over subjects.

At 1 to 4 months past infection, children younger than 3 had a median S-RBD IgG titer kBAU/L level of 342.8 (179.5-519.6); those 3 to 5 had a median level of 234.6 (113.5-347.9); 6 to 11 year olds had a median level of 164.1 (79.1-236); 12 to 18 year olds’ median level was 103.1 (46.3-170.2); and those 18 and older had a median level of 64.5 (26.2-140.9). At 10 months out and longer, when antibody levels had declined in all age groups, younger children consistently produced higher median levels than did older ones. The median antibody level for the under-3s was 146.2 (62.8-231.2); the 3 to 5 group median was 115.6 (45.9-160.6); 6 to 11 had a median level of 90.6 (62.4-111.8); the median for ages 12 to 17 was 48.6 (18.1-95.7); and the 18 and over cohort’s median was 36.7 (13.5-108.5).

In all age groups, antibody waning was fastest during the first 200 days after infection and slowed afterward. In addition, the youngest children–under age 6–experienced a more precipitous decline of antibody levels than their older cohorts. Nevertheless, detectable antibody levels remained 18 months out from infection in all age groups.

The precise reasons behind the varying antibody titer levels among different age groups are unknown, but the study’s authors hypothesize that individual cellular responses, genetic differences, environmental factors, and random variables all contribute. One possibility, they wrote, is that COVID-19 infection in the elderly generates antibodies that take aim at different proteins than antibodies generated by infections in children.

While children’s relatively high antibody levels would seem to offer protection against reinfection with COVID-19 for at least a year, the emergence of new variants means there are no guarantees. “Although it was observed that antibodies showed strong cross-reactivity to different variants, including Beta, Delta, Gamma, and Mu, for more than 1 year after infection, future studies should also confirm that long-lasting response against Omicron,” the authors wrote. “Moreover, to better understand the long-term persistence of immune protection against new emerging SARS-CoV-2 variants and to translate our data into estimations of immunity of children to subsequent infection, future research should include the evaluation of the longevity of B and T cells, which plays a key role in the human immune response.”

The study’s limitations include pandemic-related delays in accessing the clinic, resulting in a variety of follow-up times. Also, the precise date of infection could not be determined in all subjects, as some lacked a positive nasopharyngeal swab result. In these cases, the emergence of symptoms in family members provided a temporal marker.