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》

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》

Hybrid immunity after BNT162b2 Covid-19 vaccine administration in children aged 5 to 11 years.

The immune response to coronavirus disease 2019 (COVID-19) vaccination is stronger among adults with prior infection (hybrid immunity). It is important to understand if children demonstrate a similar response to better inform vaccination strategies. Our study investigated the humoral response after BNT162b2 COVID-19 vaccine doses in SARS-CoV-2 naïve and recovered children (5-11 years). A multi-institutional, longitudinal, prospective cohort study was conducted. Children were enrolled in a case-ascertained antibody surveillance study in Ottawa, Ontario from September/2020-March/2021; at least one household member was severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive on RT-PCR. In November 2021, BNT162b2 COVID-19 vaccine was authorized for children aged 5-11 in Canada. Children enrolled in the surveillance study intending to receive two vaccine doses were invited to participate in this study from November 2021-April 2022. Main exposure was prior SARS-CoV-2 infection, defined by positive RT-PCR or SARS-CoV-2 anti-N IgG antibody presence. Primary outcome was spike IgG antibody levels measured following the first vaccine dose (2-3 weeks) and second vaccine dose (3-4 weeks). Of the 153 eligible children, 75 participants (median age 8.9 IQR (7.4, 10.2) years; 38 (50.7 %) female; 59 (78.7 %) Caucasian) had complete follow-up. Fifty-four (72 %) children had prior SARS-COV-2 infection. Spike IgG antibody levels are significantly higher in SARS-CoV-2 recovered participants after receiving the first dose (p < 0.001) and the second (p = 0.01) compared to infection naïve children. SARS-CoV-2 recovered children (5-11 years) demonstrated higher antibody levels following first BNT162b2 vaccine dose compared with naïve children. Most reached antibody saturation two to three weeks after the first dose; a second dose didn't change the saturation level. A single vaccine dose in SARS-CoV-2 recovered children may be equivalent or superior to a 2-dose primary series in naïve children. Further research is needed on the durability and quality of a single vaccine dose in this population.

Tsampalieros A ，Zemek R ，Barrowman N ，Langlois MA ，Arnold C ，McGahern C ，Plint AC ，Pham-Huy A ，Bhatt M ... -  《-》

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》

Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study.

Haematological malignancies and their treatments are likely to affect SARS-CoV-2 vaccine efficacy. We aimed to evaluate serological response to BNT162b2 vaccine in patients with haematological malignancies by type of treatment. Our national prospective cohort study was done in Lithuania and assessed serological response to one and two BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine doses in healthy health-care workers and in patients with haematological malignancies. Eligible participants were aged 18 years or older, had received both vaccine doses, and had available biobanked blood samples from before vaccination and after the second dose. Biobanked samples and health data were obtained from Vilnius University Hospital Santaros Klinikos Biobank. Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG antibody) concentrations 0-10 days before the first BNT162b2 vaccine, on the day of second immunisation (around day 21), and 7 to 21 days after the second immunisation. Adverse events were assessed by a standardised questionnaire. Breakthrough infections were characterised clinically and by SARS-CoV-2 genotyping whenever possible. This study is registered with ClinicalTrials.gov, NCT04871165. Between Jan 8 and April 21, 2021, 885 participants with haematological malignancies were included in the study. 857 patients were anti-S1 IgG seronegative at timepoint 0 and constituted the main analysis cohort. The age-matched comparison was made between 315 patients with haematological malignancies who were aged 18-60 years and 67 healthy health-care workers in the same age group. Patients aged 18-60 years with haematological malignancies had lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses than did health-care workers of the same age group (median 6961 AU/mL [IQR 1292-20 672] vs 21 395 AU/mL [14 831-33 553]; p<0·0001). Compared with untreated patients with haematological malignancies (n=53; median 5761 AU/mL [629-16 141]), patients actively treated with Bruton tyrosine kinase inhibitors (BTKIs; n=44; 0 AU/mL [0-7]; p<0·0001), ruxolitinib (n=16; 10 AU/mL [0-45]; p<0·0001), venetoclax (n=10; 4 AU/mL [0-1218]; p=0·0005), or anti-CD20 antibody therapy (n=87; 17 AU/mL [1-2319]; p<0·0001) showed particularly poor anti-S1 IgG antibody responses following two BNT162b2 doses. Patients being treated with tyrosine kinase inhibitors (n=41; 10 537 AU/mL [IQR 2335-19 388]) or patients who received autologous haematopoietic stem-cell transplantation (HSCT; n=192; 6203 AU/mL [1451-16 834]) or allogeneic HSCT (n=122; 6304 AU/mL [1120-16 913]) were among the subgroups with the highest numerical responses. Nine SARS-CoV-2 infections and three COVID-19 deaths were observed among fully vaccinated patients with haematological malignancies. Patients with haematological malignancies mount blunted and heterogeneous antibody responses to the full course of BNT162b2 mRNA vaccination. Patients who are actively treated with BTKIs, ruxolitinib, venetoclax, or anti-CD20 antibody therapies seem to be the most negatively affected and might be left unprotected from SARS-CoV-2 infection. Breakthrough severe SARS-CoV-2 infections in fully vaccinated patients with haematological malignancies emphasise the importance of ongoing strict adherence to non-pharmacological interventions and household vaccination while SARS-CoV-2 is circulating in the community. Vilnius University Hospital Santaros Klinikos. For the Lithuanian translation of the abstract see Supplementary Materials section.

Maneikis K ，Šablauskas K ，Ringelevičiūtė U ，Vaitekėnaitė V ，Čekauskienė R ，Kryžauskaitė L ，Naumovas D ，Banys V ，Pečeliūnas V ，Beinortas T ，Griškevičius L ... -  《Lancet Haematology》