Antibody responses to SARS-CoV-2 are stronger and more persistent in infants

In a recent study on medrex sib*Preprint server, researchers evaluated humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants.

study: Infants and young children generate more persistent antibody responses to SARS-CoV-2 infection than adults. Image Credit: AndyDeanPhotography/Shutterstock.com

*Important Notices: medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.

Background

The breadth and persistence of anti-SARS-CoV-2 immune responses have been studied in adults and older children after infection/vaccination.

Still, the immune response in infants is not well defined. One in four of her infected infants is asymptomatic, but severe disease is more prevalent in infants than in older children.

Furthermore, little is known about how SARS-CoV-2 affects immune development and persistence of immunity in infants.

Research and Findings

In this study, we analyzed humoral responses to SARS-CoV-2 in 23 infants or young children and 19 adults. Infants and toddlers were enrolled at Cincinnati Children’s Hospital and were part of a larger prospective longitudinal birth cohort.

They were followed from birth to 500 days after the initial SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) results.

Adults with confirmed coronavirus disease 2019 (COVID-19) were followed up to 350 days after infection. Most adults (84%) did not require hospitalization and none of the adult patients developed severe symptoms.

Adults were infected between March and April 2020, whereas infants were infected between April 2020 and January 2022.

The team evaluated long-term antibody responses to various SARS-CoV-2 antigens before, during and after infection. All infants/young children develop her IgG responses to immunoglobulin A (IgA) and spike proteins and their receptor binding (RBD) and her N-terminal (NTD) domains after infection.

Pre-infection IgA and IgG levels were below the limit of detection. IgA/IgG levels peaked around 30 days post-infection and persisted for up to 500 days. Similar IgG titers were spike protein of epidemic CoVs such as SARS-CoV-1 and Middle East Respiratory Syndrome (MERS)-CoV

Furthermore, the researchers noted that pre-existing antibodies to common human CoVs (OC43 and HKU1) did not affect antibody responses to SARS-CoV-2.

IgG responses to spike, RBD and NTD in the infant cohort showed estimated half-lives of 800, 775 and 828 days, respectively, with minimal decay over time.

In contrast, IgG responses to the three antigens decayed much faster in adults, with estimated half-lives of 187-204 days. Notably, IgG antibodies against the SARS-CoV-2 nucleocapsid protein declined rapidly in infant and adult cohorts with half-lives of 116 and 83 days, respectively. Her IgG1 antibodies were the most common in both cohorts, followed by IgG2 in infants and IgG3 in adults.

Additionally, using a live viral focus reduction neutralization assay, the team assessed viral scale and durability. Neutralizing antibody (nAb) Response to wild-type SARS-CoV-2 strain.

Most infants (73%) and adults (68%) showed measurable nAb titers. nAb titers were comparable at early time points in the cohort (30-140 days post-infection).

However, nAb titers were significantly higher in infants than in adults at later time points (250–375 days post-infection). Of note, all infants had detectable nAb responses at later time points compared with 58% of adults. Spike and her RBD IgG titers were significantly correlated with her nAb titers in both cohorts.

Finally, researchers examined immune responses to SARS-CoV-2 beta, delta, and Omicron BA.1. Binding antibody responses to the beta-variant RBD were 3- and 4-fold lower in infants and adults.

Reductions in antibody titers against the delta variant were comparable between cohorts. However, it was much more pronounced for the Omicron BA.1 variant, with a 17-fold and 8-fold reduction in infants at early and late time points, respectively.

Adults showed a 12-fold and 9-fold reduction in early and late phases, respectively, relative to BA.1. Both cohorts showed a significant reduction in nAb titers against SARS-CoV-2 variants.

Infants showed a 3-fold reduction to beta variants, whereas adults showed up to 5-fold lower nAb responses.

nAb responses to BA.1 were 6- and 7-fold lower in infants and 8- and 3-fold lower in adults at early and late time points, respectively.

Conclusion

Taken together, infants/toddlers mounted more sustained binding and neutralizing responses than adults after SARS-CoV-2 infection.

Both cohorts showed robust and comparable neutralizing titers, although adults, but not infants, showed rapid decay in nAb titers. Further studies are needed to understand the mechanistic basis of these findings.

*Important Notices: medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.