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.

Impact of COVID-19 pandemic on the psychosocial well-being of children with neuromuscular disorders (preprint)

To examine the impact of COVID-19 on the psychosocial wellbeing in children with neuromuscular disorders (NMD), the parents of 41 children with NMD aged 3-12 years completed a survey during COVID-19 pandemic. The findings were compared to those of the parents of 164 matched typically-developed (TD) children. Health-related quality of life and lifestyle habits of the NMD group were compared with the TD group using independent two-sample t-test. Children with NMD with uninterrupted disease-modifying treatments showed higher PedsQL total scores during the pandemic compared to the pre-pandemic state (p=0.012). PedsQL total score in the NMD group was significantly lower than the TD group (p<0.001). Those with disrupted rehabilitation training (73.8% of NMD group) had significant lower PedsQL scores compared to those with continuous training (p = 0.012). Parental guidance on the usage of electronic devices was significantly associated with the total score of PedsQL, particularly in the NMD group (p=0.007). In conclusion, children with NMD have had a poorer quality of life than TD children during the COVID-19 pandemic. Our study highlights the importance of parental guidance on electronic device usage, the continuation of drug treatment, and rehabilitation training for the psychosocial wellbeing of children with NMD during the pandemic.

Hospital mortality in patients with rare diseases during the COVID-19 and SARS pandemics: results from a 7.5 million population

BackgroundThe threat of pandemics occur differently for different groups. The rare disease population is at particular risk of being further marginalised during pandemics.ObjectivesTo assess hospital mortality in the rare disease and general populations during the coronavirus disease of 2019 (COVID-19) and severe acute respiratory syndrome (SARS) pandemics in the 7.5 million population in Hong Kong.MethodsUsing the Clinical Data Analysis and Reporting System (CDARS), a population-level database that records all public healthcare records in Hong Kong, all admission records during the COVID-19 (January 23 – August 23, 2020) and SARS (March 11 – June 30, 2003) pandemics were extracted. Patients with rare diseases were identified using one or more of the 1,084 10th version International Classification of Diseases and Related Health Problems (ICD-10) codes cross-referenced with 467 ORPHAcodes. Admission records during the same period in 2019 and 2002 were retrieved for comparison. Primary outcomes were COVID-19/SARS mortality in hospital. Secondary outcomes were overall hospital mortality during the COVID-19 and SARS pandemic periods. Subgroup analysis by age-group (≤18, >18 to <60, ≥60) was performed to understand the mortality patterns. Logistic regression was used to estimate the odds ratios with 95% confidence intervals (CIs).ResultsDuring the COVID-19 pandemic, 407,219 patients were admitted to one or more of the 43 public hospitals in Hong Kong, of which, 39,576 (9.7%) were paediatric patients ≤18 years old, and 13,894 (3.4%) were rare disease patients. Of the 4,381 patients admitted with COVID-19, 81 (1.8%) died during the same admission, of which, 5 (6.2%) were patients with rare diseases. COVID-19-related mortality was almost exclusively seen in patients ≥60 years in both rare disease and general populations, with mortality being 21.7% and 7.4%, respectively. None of the COVID-19 patients ≤18 years died by the time of data extraction. Patients with rare diseases had an adjusted 3.4 times odds of COVID-19-related hospital mortality compared with that of the general population (95% CI 1.24–9.41). In contrast, 158,930 patients were admitted during the SARS pandemic, with 24,045 (15.1%) being ≤18 years and 5,249 (3.3%) being rare disease patients. Of the 1,449 patients admitted with SARS, 234 (16.1%) died during the same admission, of which, 1 (0.4%) was ≤18 years, and 6 (2.6%) were patients with rare diseases. While age-related increase in mortality was observed for the general population during the SARS pandemic, this pattern was not observed in the rare disease population. Rare disease patients ≤18 years had a 12.5 times higher SARS-related mortality than those in the general population (12.5% vs 1.0%). Patients admitted during the same pandemic periods without coronavirus infection had a significantly higher hospital mortality compared with those admitted one year before the pandemics (p<0.001).ConclusionsThis population-based study demonstrated the differential impacts of COVID-19 and SARS on rare disease patients in Hong Kong, a group that is currently not strategically protected. Real-time data analysis by age group within different populations could be of consideration when developing prioritisation guidelines in the future. Taken together, this study warrants cautious healthcare planning, with consideration of prioritising patients with rare diseases.