A new prospective study of 252 families with members diagnosed as having mild COVID-19 in Italy finds that, while all age-groups had detectable SARS-CoV-2 antibodies up to 1 year after infection, children—especially those younger than 3 years—had higher antibody levels than adults at all intervals tested.
In the study, published today in JAMA Network Open, a team led by University of Padua researchers enrolled 902 unvaccinated patients at a COVID follow-up clinic from Apr 1, 2020, to Aug 31, 2021. Families were included in the study if they had children younger than 15 years and at least one member who had tested positive for COVID-19 at least 4 weeks earlier.
The families underwent serologic testing for SARS-CoV-2 spike receptor-binding domain immunoglobulin G (S-RBD IgG) antibodies one to three times at 1 to 4, 5 to 10, and/or over 10 months after infection.
Detectable but declining levels
Of the 902 patients, 697 had either tested positive for COVID-19 (575; 63.7%) or had detectable SARS-CoV-2 antibodies despite no other evidence of infection (122; 17.5%), including 351 children and older siblings (average age, 8.6 years) and 346 parents (42.5 years). Among the 697 infected patients, 674 (96.7%) were asymptomatic or had mild symptoms.
At all time-points, children had significantly higher antibody concentrations than adults, with a median S-RBD IgG level fivefold higher in those younger than 3 years than in older participants. Of the 659 participants who had their antibody levels checked at least once, 657 (99.7%) still had detectable antibodies during follow-up after 64 days, while 2 of 659 (0.3%) of infected participants had negative antibody results after 556 days.
No patients reported a subsequent infection or exposure to other infected people over follow-up, but 17 participants had unexpected increases in their S-RBD IgG concentrations. Because these patients may have been unknowingly exposed, their final serum samples were excluded from analysis.
The researchers performed a longitudinal analysis using participant-paired plasma from a subgroup of 56 patients with COVID-19 who were tested at least twice for S-RBD IgG levels, with the first sample obtained at 1 to 4 months after infection. They conducted a first analysis on 31 patients sampled at, on average, 89.2 and 199.2 days, and a second analysis on 40 patients with samples collected at an average of 81.9 and 380 days (medium and long intervals, respectively). They sampled 22 patients three times, contributing to both subgroups.
Both analyses were stratified by age-group: younger than 6 years, 6 to 18, and older than 18. While all age-groups had detectable antibodies at both time-points, their antibody levels declined progressively, ranging from 2.0- and 2.3-fold decreases at the medium interval to 2.5- to 3.6-fold drops at the long interval.
In an analysis of 194 samples from a subgroup of 84 infected participants tested for antibodies at least twice, regardless of when the first serum was obtained, antibodies were still detectable at 18 months post-infection. Antibody concentrations waned faster in the first 200 days after infection than in subsequent days. Relative to adults and children 6 and older, younger children demonstrated faster early antibody waning.
Determining the optimal vaccine schedule
The authors said the results address a gap in the understanding of antibody persistence after COVID-19 infection in asymptomatic or mildly ill children, who have a role in silently transmitting the virus.
"This study may provide an important basis to determine the schedule of COVID-19 vaccination in non-previously infected children and of booster immunization in pediatric patients who have already experienced COVID-19," they wrote.
The researchers said that the differences in immune response among age-groups are likely due to factors such as specific cellular responses and genetics.
They called for research into the durability of antibodies against the Omicron variant and future variants and the longevity of B and T immune-cell responses. "In fact," they wrote, "although we focused on the antibody responses to infection in this analysis, cellular immune responses are also likely to play an important role in protection against SARS-CoV-2 subsequent infection, as we and others have previously reported."