A longitudinal seroepidemiology study to evaluate antibody response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Canada from July 2020 to April 2022: Alberta COVID-19 Childhood Cohort (AB3C) Study.

Measurement of SARS-CoV-2 antibody seropositivity is important to accurately understand exposure to infection and/or vaccination in specific populations. This study aimed to estimate the serologic response to SARS-CoV-2 virus infection and vaccination in children in Calgary, Alberta over a two-year period. Children with or without prior SARS-CoV-2 infections, were enrolled in Calgary, Canada in 2020. Venous blood was sampled 4 times from July 2020 to April 2022 for SARS-CoV-2 nucleocapsid and spike antibodies. Demographic and clinical information was obtained including SARS-CoV-2 testing results and vaccination records. 1035 children were enrolled and 88.9% completed all 4 visits; median age 9 years (IQR: 5,13); 519 (50.1%) female; and 815 (78.7%) Caucasian. Before enrolment, 118 (11.4%) had confirmed or probable SARS-CoV-2. By April 2022, 39.5% of previously uninfected participants had a SARS-CoV-2 infection. Nucleocapsid antibody seropositivity declined to 16.4% of all infected children after more than 200 days post diagnosis. Spike antibodies remained elevated in 93.6% of unvaccinated infected children after more than 200 days post diagnosis. By April 2022, 408 (95.6%) children 12 years and older had received 2 or more vaccine doses, and 241 (61.6%) 5 to 11 year-old children had received 2 vaccine doses. At that time, all 685 vaccinated children had spike antibodies, compared with 94/176 (53.4%) of unvaccinated children. In our population, after the first peak of Omicron variant infections and introduction of COVID-19 vaccines for children, all vaccinated children, but just over one-half of unvaccinated children, had SARS-CoV-2 spike antibodies indicating infection and/or vaccination, highlighting the benefit of vaccination. It is not yet known whether a high proportion of seropositivity at the present time predicts sustained population-level protection against future SARS-CoV-2 transmission, infection or severe COVID-19 outcomes in children.

Doucette EJ ，Gray J ，Fonseca K ，Charlton C ，Kanji JN ，Tipples G ，Kuhn S ，Dunn J ，Sayers P ，Symonds N ，Wu G ，Freedman SB ，Kellner JD ... -  《PLoS One》

Pediatric antibody responses to SARS-CoV-2 after infection and vaccination in Calgary, Canada.

There are few reports of longitudinal serologic responses in children following Sars-CoV-2 infection and vaccination. This study describes longitudinal SARS-CoV-2 antibody responses following infection, vaccination, or both (hybrid immunity) in a cohort of Canadian children. The objectives of our study were to compare antibody levels following SARS-CoV-2 infection, vaccination, and hybrid immunity and to examine antibody decline after final antigen exposure. The Alberta Childhood COVID-19 Cohort (AB3C) study was a prospective longitudinal cohort study conducted from July 2020 to September 2022 with repeat sampling across 5 visits. Children under 18 years of age were enrolled for serial measurement of antibody responses to SARS-CoV-2 virus vaccine and infection. The final sample size was 919; participants were 50.5% female, 48.2% were > 12 years and 88.5% were white ethnicity. The median peak spike IgG level of those with only infection was not different from those with no vaccination or infection (233 AU/mL (IQR: 99-944 AU/mL) vs. 3 AU/mL (IQR: 1-5 AU/mL; P = 0.1765). Participants with infections after vaccination had higher IgG levels than those where infection preceded vaccination (median: 36,660 (IQR: 22,084 - 40,000 AU/mL) vs. 17,461 AU/mL (IQR: 10,617 - 33,212 AU/mL); P < 0.0001). In a linear mixed methods model, children with infection-only had low levels of antibody that stayed stable over the study duration without further antigen exposures. Those with infection after vaccination had the slowest rate of antibody decline over time at 4% (95%CI: 2-5%) per week, compared with children where infection preceded vaccine 7% (95%CI: 6-8%) per week. Children with hybrid immunity conferred through vaccination (2 + doses) followed by a SARS-CoV-2 infection had the highest and longest lasting antibody levels, compared to children who had an infection followed by vaccination, vaccination-only, or infection-only. The longer-term clinical importance of these findings, related to prevention of repeated infections and severe outcomes and need for further vaccine doses, is not yet known.

Ricketson LJ ，Doucette EJ ，Alatorre I ，Tarannum T ，Gray J ，Booth W ，Tipples G ，Charlton C ，Kanji JN ，Fonseca K ，Kellner JD ... -  《BMC INFECTIOUS DISEASES》

Pre-Vaccine Positivity of SARS-CoV-2 Antibodies in Alberta, Canada during the First Two Waves of the COVID-19 Pandemic.

Charlton CL ，Nguyen LT ，Bailey A ，Fenton J ，Plitt SS ，Marohn C ，Lau C ，Hinshaw D ，Lutsiak C ，Simmonds K ，Kanji JN ，Zelyas N ，Lee N ，Mengel M ，Tipples G ... -  《Microbiology Spectrum》

Post-vaccination SARS-CoV-2 seroprevalence in children aged 3-11 years and the positivity in unvaccinated children: A retrospective, single-center study.

To analyze the positivity and levels of SARS-CoV-2 antibodies in vaccinated children to evaluate the humoral immune response of vaccination on pediatric population. Analysis on the causes of antibody positivity in unvaccinated children. A retrospective study was conducted on children who were admitted to the Children's Hospital Affiliated to Capital Institute of Pediatrics. The clinical data of serological testing of SARS-CoV-2 immunoglobulin M (IgM) and IgG antibodies were collected from SARS-CoV-2 vaccinated or unvaccinated children with no evidence of prior novel coronavirus infection. Chemiluminescence immunoassay was utilized for the in vitro determination of SARS-CoV-2 antibodies. A total of 3,321 healthy children aged 6-11 years received two doses of inactivated SARS-CoV-2 vaccine. At 1 month after the second dose, the positive rate (96.5%) and levels [8.039 (interquartile range (IQR), 6.067-9.098)] of SARS-CoV-2 IgG antibodies reached the peak and remained at a high level for 2-3 months, after which the positive rate and level of vaccine-induced IgG antibody gradually decreased. Compared with 1 month after the second dose of vaccine, the positive rate of IgG antibody decreased to 70.4% at 7 months, and the antibody level decreased by 69.0%. A total of 945 children aged 3-5 years received one or two doses of inactivated vaccine. The positive rate and levels of SARS-CoV-2 IgG antibody in participants remained high for 3 months after vaccination. There was no gender-based difference in positive rate of IgG antibody in children aged 3-11 years old (P>0.05). Among the 5,309 unvaccinated children aged 0 day to 11 years, 105 (2.0%) were positive for SARS-CoV-2 IgG antibody, which was associated with passive infusion. The maternal humoral response to COVID-19 vaccination in noninfected pregnant women was transferred through the placenta to the fetus, and some children obtained SARS-CoV-2-positive antibodies through blood transfusion. Inactivated SARS-CoV-2 vaccines could induce robust humoral immune response that gradually declined within several months after the second dose. Therefore, it helps to determine whether children receive a booster dose and elicit a long-term memory immune response. Positive SARS-CoV-2 antibodies in unvaccinated children were associated with passive IgG antibody infusion.

Li J ，Ge M ，Dai S ，Song Q ，Liu W ，Wang Y ，Xu W ，Ma L ... -  《Frontiers in Immunology》

SARS-CoV-2 Infection-and mRNA Vaccine-induced Humoral Immunity among Schoolchildren in Hawassa, Ethiopia.

With the persisting low vaccination intake, particularly in children of low-and middle-income countries (LMICs), seroepidemiological studies are urgently needed to guide and tailor COVID-19 pandemic response efforts in schools and to put mitigation strategies in place for a future post-pandemic resurgence. However, there is limited data on SARS-CoV-2 infection-induced and vaccine-induced humoral immunity in schoolchildren in LMICs, including Ethiopia. As the spike receptor binding domain (RBD) is the major target for neutralization antibodies and useful to predict the correlates of protection, we used an in-house anti-RBD IgG ELISA to assess and compare infection-induced antibody response at two-time points and BNT162b2 (BNT) vaccine-induced antibody response at a one-time point in schoolchildren in Hawassa, Ethiopia. In addition, we measured and compared the levels of binding IgA antibodies to spike RBD of SARS-CoV-2 Wild type, Delta, and Omicron variants in a small subset of unvaccinated and BNT-vaccinated schoolchildren. When we compare SARS-CoV-2 infection-induced seroprevalences among unvaccinated school children (7-19 years) at the two blood sampling points with a 5-month interval, we observed an over 10% increase, from 51.8% (219/419) in the first week of December 2021 (post-Delta wave) to 67.4% (60/89) by the end of May 2022 (post-Omicron wave). Additionally, we found a significant correlation (p = 0.001) between anti-RBD IgG seropositivity and a history of having COVID-19-like symptoms. Compared to the levels of SARS-CoV-2 infection-induced anti-RBD IgG antibodies before vaccination, higher levels of BNT vaccine-induced anti-RBD IgG antibodies were observed even in SARS-CoV-2 infection-naïve schoolchildren of all age groups (p = 0.0001). Importantly, one dose of the BNT vaccine was shown to be adequate to elicit a strong antibody response in schoolchildren with pre-existing anti-RBD IgG antibodies comparable to that of SARS-CoV-2 infection-naive schoolchildren receiving two doses of BNT vaccine, suggesting a single dose administration of the BNT vaccine could be considered for schoolchildren who had prior SARS-CoV-2 infection when a shortage of vaccine supply is a limiting factor to administer two doses irrespective of their serostatus. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Irrespective of schoolchildren's vaccination status, we observed a similar pattern of significantly higher levels of IgA antibodies to Delta-RBD than to Omicron-RBD (p < 0.001) in a randomly selected subset of schoolchildren, yet comparable to Wuhan-RBD, suggesting these schoolchildren were more likely to have had SARS-CoV-2 infection with Delta variant. Additionally, we noted a broader IgA antibody reactivity to SARS-CoV-2 variants in vaccinated schoolchildren with prior SARS-CoV-2 infection, supporting the superiority of hybrid immunity. Our serological data indicate a significant increase in SARS-CoV-2 seroprevalence in children at a post-Omicron five-month follow-up compared to a post-Delta enrolment. Despite the small sample size of study participants, the BNT vaccine is shown to be immunogenic and safe for schoolchildren. Hybrid immunity would likely provide a broader humoral immunity against Wuhan strain, Delta, and Omicron variants than natural infection or vaccination alone does. However, future longitudinal cohort studies in SARS-CoV-2-naïve and COVID-19-recovered schoolchildren receiving the BNT vaccine are needed for a better understanding of the kinetics, breadth, and durability of BNT vaccine-induced multivariant-cross reactive immunity.

Merid Y ，Tekleselasie W ，Tesfaye E ，Gadisa A ，Fentahun D ，Abate A ，Alemu A ，Mihret A ，Mulu A ，Gelanew T ... -  《Frontiers in Immunology》