Comparing self-reported reactogenicity between adolescents and adults following the use of BNT162b2 (Pfizer-BioNTech) messenger RNA Covid-19 vaccine: a prospective cohort study

Objectives: Although clinical data have shown that the BNT162b2 vaccine, which is widely used in many countries, is safe and effective as a protection against the Covid-19 infection, extant research in adverse reactions using real-world data of various socio-demographic characteristics is scant. Methods: We conducted a prospective cohort study to compare age differences in self-reported reactogenicity of BNT162b2 in Hong Kong. A total of 1,516 participants were intensively followed up for two weeks following both doses of BNT162b2 vaccination, during which their basic demographic, health conditions, and medication information were collected. Results: Results from generalized mixed model showed that compared with adults aged 18 – 59, older adults aged 60 or above had a lower risk of adverse reactions, and adolescents aged 12 – 17 had a moderately higher risk. Conclusions: Results of this study should be informative to parents considering BNT162b2 vaccination for their children in that moderately increased reactogenicity compared with adults is anticipated

Linking cohort-based data with electronic health records: a proof-of-concept methodological study in Hong Kong.

OBJECTIVES: Data linkage of cohort-based data and electronic health records (EHRs) has been practised in many countries, but in Hong Kong there is still a lack of such research. To expand the use of multisource data, we aimed to identify a feasible way of linking two cohorts with EHRs in Hong Kong. METHODS: Participants in the 'Children of 1997' birth cohort and the Chinese Early Development Instrument (CEDI) cohort were separated into several batches. The Hong Kong Identity Card Numbers (HKIDs) of each batch were then uploaded to the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to retrieve EHRs. Within the same batch, each participant has a unique combination of date of birth and sex which can then be used for exact matching, as no HKID will be returned from CDARS. Raw data collected for the two cohorts were checked for the mismatched cases. After the matching, we conducted a simple descriptive analysis of attention deficit hyperactivity disorder (ADHD) information collected in the CEDI cohort via the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour Scale (SWAN) and EHRs. RESULTS: In total, 3473 and 910 HKIDs in the birth cohort and CEDI cohort were separated into 44 and 5 batches, respectively, and then submitted to the CDARS, with 100% and 97% being valid HKIDs respectively. The match rates were confirmed to be 100% and 99.75% after checking the cohort data. From our illustration using the ADHD information in the CEDI cohort, 36 (4.47%) individuals had ADHD-Combined score over the clinical cut-off in the SWAN survey, and 68 (8.31%) individuals had ADHD records in EHRs. CONCLUSIONS: Using date of birth and sex as identifiable variables, we were able to link the cohort data and EHRs with high match rates. This method will assist in the generation of databases for future multidisciplinary research using both cohort data and EHRs

Multimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong

Prior research using electronic health records for Covid-19 vaccine safety monitoring typically focuses on specific disease groups and excludes individuals with multimorbidity, defined as ≥2 chronic conditions. We examine the potential additional risk of adverse events 28 days after the first dose of CoronaVac or Comirnaty imposed by multimorbidity. Using a territory-wide public healthcare database with population-based vaccination records in Hong Kong, we analyze a retrospective cohort of patients with chronic conditions. Thirty adverse events of special interest according to the World Health Organization are examined. In total, 883,416 patients are included and 2,807 (0.3%) develop adverse events. Results suggest vaccinated patients have lower risks of adverse events than unvaccinated individuals, multimorbidity is associated with increased risks regardless of vaccination, and the association of vaccination with adverse events is not modified by multimorbidity. To conclude, we find no evidence that multimorbidity imposes extra risks of adverse events following Covid-19 vaccination

Self-reported reactogenicity of CoronaVac (Sinovac) compared with Comirnaty (Pfizer-BioNTech): A prospective cohort study with intensive monitoring

OBJECTIVE: CoronaVac (Sinovac) Covid-19 vaccine has recently been approved for emergency use by the World Health Organization. However, data on its reactogenicity in real-world settings is scant. This study aimed to compare self-reported post-vaccination adverse reactions between CoronaVac and Comirnaty (Pfizer-BioNTech). METHODS: We adopted a prospective cohort study design using online surveys from the day of first-dose vaccination with intensive follow-up through two weeks after the second dose (11 time points). The primary outcome was adverse reactions (any versus none) and secondary outcomes were the sub-categories of adverse reactions (local, systemic, and severe allergic reactions). Potential effect modification across multimorbidity status, older age, and sex was examined. RESULTS: In total, 2,098 participants who were scheduled to complete the 14th-day survey were included, with 46.2% receiving Comirnaty. Retention rate two weeks after the second dose was 81.0% for the CoronaVac group and 83.6% for the Comirnaty group. Throughout the follow-up period, 801 (82.7%) of those receiving Comirnaty and 543 (48.1%) of those receiving CoronaVac reported adverse reactions. Adjusted analysis suggested that compared with Comirnaty, CoronaVac was associated with 83%-reduced odds of any adverse reactions [adjusted odds ratio (AOR) = 0.17, 95% confidence interval (CI) 0.15–0.20], 92%-reduced odds of local adverse reactions (AOR = 0.08, 95% CI 0.06–0.09), and 76%-reduced odds of systemic adverse reactions (AOR = 0.24, 95% CI 0.16–0.28). No significant effect modification was identified. CONCLUSION: This post-marketing study comparing the reactogenicity of Covid-19 vaccines suggests a lower risk of self-reported adverse reactions following vaccination with CoronaVac compared with Comirnaty

Human tartrate-resistant acid phosphatase becomes an effective ATPase upon proteolytic activation

Proteolytic cleavage in an exposed loop of human tartrate-resistant acid phosphatase (TRAcP) with trypsin leads to a significant increase in activity. At each pH value between 3.25 and 8.0 the cleaved enzyme is more active. Substrate specificity is also influenced by proteolysis. Only the cleaved form is able to hydrolyze unactivated substrates efficiently, and at pH >6 cleaved TRAcP acquires a marked preference for ATP. The cleaved enzyme also has altered sensitivity to inhibitors. Interestingly, the magnitude and mode of inhibition by fluoride depends not only on the proteolytic state but also pH. The combined kinetic data imply a role of the loop residue D158 in catalysis in the cleaved enzyme. Notably, at low pH this residue may act as a proton donor for the leaving group. In this respect the mechanism of cleaved TRAcP resembles that of sweet potato purple acid phosphatase

Redox-stable cyclic peptide inhibitors of the SPSB2-iNOS interaction

SPSB2 mediates the proteasomal degradation of iNOS. Inhibitors of SPSB2-iNOS interaction are expected to prolong iNOS lifetime and thereby enhance killing of persistent pathogens. Here, we describe the synthesis and characterization of two redox-stable cyclized peptides containing the DINNN motif required for SPSB2 binding. Both analogues bind with low nanomolar affinity to the iNOS binding site on SPSB, as determined by SPR and (19)F NMR, and efficiently displace full-length iNOS from binding to SPSB2 in macrophage cell lysates. These peptides provide a foundation for future development of redox-stable, potent ligands for SPSB proteins as a potential novel class of anti-infectives