Vaccine hesitancy, reactogenicity and immunogenicity of BNT162b2 and CoronaVac in pediatric patients with neuromuscular diseases (preprint)

Introduction COVID-19 causes global health and psychosocial devastation, particularly to high-risk patients such as those with neuromuscular diseases (NMDs). The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two novel COVID-19 vaccines widely used across the world that confer immune protection to healthy individuals. However, hesitancy towards COVID-19 vaccination was common for patients with NMDs early in the pandemic due to the paucity of data on the safety and efficacy in this specific patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for these patients and included the assessment of the reactogenicity and immunogenicity of these two vaccines. Methods Pediatric patients were screened from our NMD registry. For the vaccine hesitancy arm, those aged 8-18 years with no cognitive delay were invited to complete surveys in January and April 2022. For the reactogenicity and immunogenicity arm, patients aged 2-21 years were enrolled for COVID-19 vaccination between June 2021 to April 2022. Participants recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before BNT162b2 or CoronaVac and within 49 days after vaccination to measure their serological antibody responses as compared to healthy children and adolescents. Results Forty-one patients completed vaccine hesitancy surveys for both timepoints, and 22 joined our reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81-75.1, p=0.010). Pain at the injection site, fatigue and myalgia were the commonest ARs. Most ARs were mild (75.5%, n=71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of BNT162b2 or CoronaVac, although there was lower neutralization against the Omicron BA.1 variant. Discussion This study demonstrated vaccine hesitancy amongst patients with NMDs was influenced by family members and changed across time. BNT162b2 and CoronaVac were safe and immunogenic even for patients on low-dose corticosteroids. Future research is required to assess the durability of the COVID-19 vaccines, the effectiveness of booster doses and other routes of administration against emerging SARS-CoV-2 variants for these patients.

Humoral and Cellular Immunogenicity and Safety of 3 Doses of CoronaVac and BNT162b2 in Young Children and Adolescents with Kidney Diseases (preprint)

Background: Patients with kidney diseases are at risk of severe complications from COVID-19, yet little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated, 3-dose primary series of COVID-19 vaccines among 64 pediatric chronic kidney disease patients (mean age 12.2; 32 male) with or without immunosuppression, dialysis, or kidney transplant. CoronaVac was given to those aged <5 years, 0.1ml BNT162b2 to those aged 5-11 years, and 0.3ml BNT162b2 to those aged 11-18 years. Results: Antibody responses including S-RBD IgG (90.9-100% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6-94.0%) were significantly elicited by 3 doses of any vaccine. T cell responses were also elicited. Weaker neutralization responses were observed among kidney transplant recipients and non-dialysis children receiving rituximab for glomerular diseases. Neutralization was reduced against Omicron BA.1 compared to wild-type (post-dose 3 sVNT% level; 84% vs 27.2%; p<0.0001). However, T cell response against Omicron BA.1 was preserved, which likely confer protection against severe COVID-19. Hybrid immunity was observed after vaccination in infected patients, as evidenced by higher Omicron BA.1 neutralization response among infected patients receiving 2 doses than those uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusions: Our findings support that an accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after the third dose of BNT162b2 in healthy adolescents (preprint)

High effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 6 months after 2 doses, S IgG, S IgG Fc receptor-binding, S-RBD IgG and neutralizing antibody responses waned significantly, yet neutralizing antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, and PRNT50 against Omicron BA.2, as well as preserved cellular responses against BA.1 S. Sera from 100% and 96% of adolescents tested at 1 and 6 months after 2 doses could also neutralize BA.1. Based on PRNT50, we predict 92%, 89% and 68% effectiveness against COVID-19 with WT, BA.2 and BA.5 1 month after 3 doses. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after 3 doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

Safety and Immunogenicity of 3 Doses of BNT162b2 and CoronaVac in Children and Adults with Inborn Errors of Immunity (preprint)

Background: Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in adult and pediatric patients with inborn errors of immunity (IEIs) remain unknown. Intradermal vaccination may improve immunogenicity in immunocompromised patients. Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Methods Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. Adverse reactions and adverse events were tracked for 7 and 28 days after each dose. Antibody responses assessed included binding IgG antibody to wild-type (WT) spike receptor-binding domain (S-RBD IgG) and surrogate neutralization activity to WT and BA.1 viruses. T cell responses were examined by intracellular cytokine staining following stimulation with SARS-CoV-2 peptide pool(s). Results No safety concerns were identified. Inadequate antibody responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients. Intradermal third dose vaccine led to high antibody response in 4 patients. Conclusions The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic (preprint)

Background The lifestyles of children and adolescents have changed extensively during the COVID-19 pandemic due to school suspension and social distancing measures, which can affect their sleep health. Existing studies have used convenient samples and focused on the initial months of the pandemic. Method As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. We investigated the pandemic's effects on sleep parameters using multivariate regression, adjusting for age, sex, household income, seasonality and presence of mental disorders, and the moderators and mediators of the effects. Findings Between 1 September 2019 and 2 June 2021, 791 primary and 442 secondary school students were recruited and analysed. Assessment during COVID predicted a longer sleep latency in both groups on school days (95% CI= 1.0-5.2 minutes, adjusted p-value= 0.010; and 95% CI= 3.9-13.0 minutes, adjusted p-value= 0.004, respectively) and non-school days (95% CI= 1.7-7.2 minutes, adjusted p-value= 0.005; 95% CI= 3.4-13.7 minutes, adjusted p-value= 0.014, respectively). Low household income was a moderator for later bedtime (adjusted p-value= 0.032) and later sleep onset (adjusted p-value= 0.043) during non-school days among secondary school students. Sex and digital leisure time were respectively not a moderator and mediator of the pandemic's effect on sleep parameters. Interpretation Changes associated with COVID have a widespread and enduring effect on the sleep health of school-aged students in Hong Kong. Household income plays a role in adolescent sleep health resilience, and effects of anti-epidemic measures on the health gaps of the youth should be considered. Funding Government of the Hong Kong Special Administrative Region, Food and Health Bureau, Health and Medical Research Fund (Ref. No.: MHS-P1(Part 1)-CUHK).

Immunogenicity and reactogenicity of SARS-CoV-2 mRNA and inactivated vaccines in healthy adolescents (preprint)

For SARS-CoV-2 vaccines, efficacy data for BNT162b2 but not CoronaVac are available in adolescents. Phase II/III studies focused on neutralizing antibody responses in adolescents, neglecting binding antibody and cellular responses that are also important against SARS-CoV-2. Therefore, we conducted a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of these 2 vaccines in healthy adolescents. One-dose BNT162b2 outcomes were also assessed since it had been recommended in some localities due to the risk of myocarditis. Antibodies and T cell immune responses were non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N=116) and CoronaVac (CC, N=123) versus adults after 2 doses of the same vaccine (BB, N=147; CC, N=141) but not in adolescents after 1 dose of BNT162b2 (B, N=116). CC induced SARS-CoV-2 nucleocapsid (N) and N C-terminal domain seroconversion in more adolescents than adults. Adverse reactions were mostly mild for both vaccines and more frequent for BNT162b2. We confirmed higher S, neutralizing, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC. This is the first study to show similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2 in adolescents. The implications of the differential ability to induce S- and non-S-specific antibody and T cell responses on the durability of protection and protection against virus variants by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines in the world, should be further investigated. Our results support the use of both vaccines in adolescents.