Waning antibody responses in SARS-CoV-2-infected children and adults over time

In a recent study posted to the medRxiv* preprint server, researchers evaluated the duration of antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Background

Since the coronavirus disease 2019 (COVID-19) pandemic began, more than 28 million children have contracted SARS-CoV-2 infection globally, with around 13,000 deaths. Children typically develop milder symptoms and less severe illnesses than adults.

Children were increasingly affected during the recent surge of COVID-19 infections, and vaccines against SARS-CoV-2 were approved only recently for those above five years.

According to two recent studies, children develop comparable levels of neutralizing antibodies (nAbs) after natural infection, which persist for a similar duration as adults. Yet, some other studies reported lower levels and duration of nAbs in children with the mild-to-severe disease than in adults.

Whether age, COVID-19 severity, SARS-CoV-2 variants, or other factors are responsible for the conflicting results remains unclear. Nevertheless, it is critical to understand the breadth and durability of immunity offered by natural infection to inform future policy measures.

The study

In the present study, researchers assessed the differential levels and duration of nAbs and immunoglobulin G (IgG) in children relative to adults. Children below 18 years and adults were included between June 18 and December 29, 2020, in four categories: symptomatic with positive polymerase chain reaction (PCR) result (SP+), symptomatic but PCR-negative or untested (SP-), asymptomatic exposed (AE), and asymptomatic without any known exposure (ANE).

Children with symptomatic COVID-19 reported fever, cough, chills, headache, shortness of breath, sore throat, a new loss of smell or taste, diarrhea, or muscle pain. Those in the AE category were in contact with a symptomatic and PCR-positive individual, whereas those in the ANE group had no such encounter. Immunocompromised subjects, convalescent plasma recipients, and those with acute illness at the time of enrolment were excluded from the study.

Blood samples were obtained at two different time points: during and after six months of enrollment. Luminex xMAP technology, a multiplex platform based on flow-cytometry, was customized for quantitating serology and binding inhibition of angiotensin-converting enzyme-2 (ACE2) and receptor-binding domain (RBD) by antibodies in a single assay.

Microspheres coated with antigens were used to quantify IgG against nucleocapsid (N) protein, spike (S) protein’s N-terminal domain (NTD), and mutant epitopes of RBD. Antibodies against different variants that emerged before SARS-CoV-2 Delta and Omicron were also tested.

Results

Three hundred and forty-four adults and 94 children were recruited; children from four groups but adults from only the SP+ group were evaluated for antibody duration. Pediatric subjects were aged between 6 months and 17 years. Moreover, 13% of adults and children were Black, and 6% of children and 13% of adults were Hispanic.

All SP+ children developed nAbs compared to 30% of SP-, 39% AE, 5% ANE children, and 81% of adults. There were no differences in the antibody titers between nAb-positive symptomatic and asymptomatic children. Twenty-two children were nAb-positive at enrollment, and 17 displayed nAbs after six months. Antibody titers were significantly reduced in both symptomatic and asymptomatic children. After six months, only 50% of SP+ adults had nAbs, while 88% of SP+ children showed nAbs. Both SP+ children and adults lost nAb titers over six months, with a higher mean difference in adults than children, although this was statistically insignificant.

IgG levels were comparable in adults and children, but anti-RBD1 IgG antibodies were higher in children than adults at the initial visit. No significant differences were observed in IgG levels against total S protein or NTD between children and adults. SP+ children demonstrated robust IgG responses to every tested S protein variant, with higher levels against K417N and E484Q variants than (SP+) adults.

While children were not vaccinated during the study period, seven adults had been vaccinated between the two visits, and antibody titers were compared between vaccinated and non-vaccinated adults at six months. All vaccinated adults had nAbs in contrast to just 50% of non-vaccinated adults with nAbs. Antibodies against S protein, RBD1, RBD2, and NTD increased in adults post-vaccination.

Still, anti-N antibodies waned in vaccinated and non-vaccinated adults, given that vaccines target the S protein. Moreover, antibody titers against different variants’ S protein increased in adults post-vaccination, but non-vaccinated adults showed lower antibody titers against S variants.

Conclusions

The authors observed robust nAb responses in symptomatic or asymptomatic children, which last longer in children than in adults. Nonetheless, both children and adults exhibited a waning of antibody titers over time. Symptomatic children develop IgG responses to multiple SARS-CoV-2 S protein variants at a similar or higher level compared to adults.

Vaccinated adults had significantly higher nAb and IgG levels than with COVID-19 infection alone. Although natural infection elicited robust immunity in children, the significant waning of nAbs over time highlights the potential need to vaccinate children.

*Important notice

medRxiv 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.