Even as the outbreak of acute coronavirus disease 2019 (COVID-19) spread worldwide, due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it was observed that children were largely spared from the severe effects of the disease. Among those who were infected, multisystem inflammatory syndrome in children (MIS-C) was rare.
Study: Long-term antibody response to SARS-CoV-2 in children. Image Credit: FamVeld/Shutterstock
Still, vaccination of this age group has proceeded apace in many countries, but with large differences between regions. For the last few months, the vaccination has been carried out even in children under 5 years, on a large scale. Yet the latest variant of the virus to emerge, Omicron, appears to evade the host neutralizing antibody response following vaccination.
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Some reports do suggest that Omicron is causing more hospitalizations among children than any other variant. Yet, few studies have taken place to understand how antibody responses persist over time after natural infection in children.
The current study, available on the medRxiv* preprint server, attempts to fill this gap.
The study
The study was based on data from a prospective cohort study on children and their households, called the C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study. It included over 6,000 children screened by nasal swab and polymerase chain reaction (PCR) for the virus.
At the time, between May 11 and June 30, 2020, following a lockdown, the incidence was low. The screening tests used included nasopharyngeal swab-PCR. About 4,700 were screened with the Roche nucleocapsid protein total IgA/IgM/IgG test. The DiaSorin S1/S2 spike IgG was used as the confirmatory test.
Any positive test was followed up and testing repeated, in addition to serology of all household contacts. Follow-up occurred for six months. The study identified 67 children as seropositive for both tests, accounting for 1.44% of all tested.
Fifty of the children were recalled for testing within six days, and all were positive. The median time of testing was 83 days from symptom onset.
Within the age group of 0-18 years, seroconversion was more likely among older children. Children aged 12-18 years had seroconversion rates of almost 50%, and those aged 6-12 years >40%, while only about one in ten of those aged 6 years or less were seropositive. Thus, the odds of seroconversion were three times higher in the oldest age group among children.
Seropositive children were two years older, on average, than seronegative children, at ~10 vs 8 years, respectively. The odds of seroconversion among children below 18 years increased by 1.11 per year.
In about 30% of children, other underlying medical conditions were present, but seroconversion rates were not affected by this factor. However, seropositivity was more common among children who were up to date with childhood vaccinations. Seropositive children more often reported the presence of anosmia in the last 14 days prior to screening, while other symptoms were similar in incidence.
Exposure history
Exposure history was available for 119 of the children along with antibody tests. Of these, almost a quarter (23%, or 27 children) were seropositive. All 20 who came for recall testing were positive for both tests. Among the seropositive children who had a history of contact with a known case, 93% had contact within the family, but only 7% were in contact with known cases from outside the family.
Testing of the household contacts of the seropositive childhood cases showed incomplete seroconversion within the family in most cases. Moreover, the younger the index case, the lower the overall seroconversion rate was.
When the index case in the household was an adult, the risk of seroconversion was almost 80% higher than if the index case was a child. That is, the average seroconversion rate was 74% when the index case was above the age of 18, but only about 50% with pediatric index cases.
Persistent antibodies
Children continued to test positive for anti-SARS-CoV-2 antibodies for up to 9 months from symptom onset. No evidence of acute infection was found at 3 and 6 months of follow-up. However, almost all showed detectable specific antibodies, both anti-nucleocapsid IgA, IgG and IgM, as well as spike IgG antibodies.
Spike IgG concentrations were higher in children at all time points up to 270 days, but waned over time in both children and adults. With children, the initial waning occurred faster and more steeply.
At 90 days, children had 75% higher spike IgG levels, but at 180 days and 270 days, the respective ratios were 40% and 55% higher. At all points, children had higher serum anti-spike IgG antibody concentrations than adults.
Implications
The study shows lower seroconversion rates among children. This could be due to the lower secondary attack rates among young children, and among children overall compared to adults. However, it should be remembered that contacts between peers of similar age are the most likely to be associated with viral spread.
During lockdown, children were cut off from contact with each other, and this may be a contributing factor to the lower observed seroconversion and transmission risk in this age group.
Again, children who become infected are typically isolated, whereas for adult caregivers, this may be more difficult. Thus, transmission from children to adults is lower than in the other direction, despite similar nasopharyngeal viral loads. Other factors include differences in droplet and aerosol formation, in the anatomy of the upper airways and lung, and the viral tropism for these regions, in adults vs children.
However, newer variants of the virus, especially Delta and Omicron, have been reported to be more infectious and to cause more hospitalizations among children compared to the ancestral variants. These are associated with higher viral loads, increased viral replication within the airway and higher viral fitness.
Another significant finding is the persistence of detectable anti-SARS-CoV-2 antibodies at all time points up to 9 months, at higher levels than in adults, despite a faster initial waning.
In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroconversion rates in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.”
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Article Revisions
- May 11 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
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