Search

After keeping infections at bay for two years, Hong Kong experienced a surge of Omicron BA.2 infections in early 2022 that overwhelmed the health care system, isolation facilities, and contact tracing capacity, leading to one of the highest per-capita death rates of COVID-19 in early 2022. The outbreak occurred against a backdrop of a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures. Using genome sequences and epidemiological data from this time, we reconstruct the epidemic trajectory of the BA.2 wave, estimate transmission and incidence rates, and evaluate the effectiveness of policy changes. We identify an increase in the effective reproductive rate (Re) to 9.5 in mid-January 2022, which preceded real-time estimates of transmission (Rt), revealing that BA.2 community transmission was under-ascertained weeks before the epidemic appeared to surge in mid-February 2022. Due to this, public health measures were relaxed in early February (Spring Festival) while Re increased and remained > 1 throughout February. An independent estimation of point prevalence and incidence using phylodynamics also indicates extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. This study demonstrates that relying on Rt estimation methods dependent on case reporting can misinform epidemic response planning, sometimes with substantial consequences. There is a need for future research and implementation of improved estimates of epidemic growth in near real-time that combine multiple disparate data sources to better inform outbreak response policy.

Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections. In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity and were under neutral to purifying selection at the full genome level compared to non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty and CoronaVac vaccinated individuals did not increase levels of non-synonymous mutations and did not change the direction of selection pressure. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 sequence diversification. Our findings suggest that vaccination does not increase exploration of SARS-CoV-2 protein sequence space and may not facilitate emergence of viral variants.

Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutralization in individuals with different exposure to SARS-CoV-2 infection and vaccination, we here use a multiplex surrogate neutralization assay based on virus spike receptor binding domains of multiple SARS-CoV-2 VoC, as well as related bat and pangolin viruses. We include sera from cohorts of individuals vaccinated with two or three doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 infection. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or Coronavac elicit the highest and broadest neutralization across VoCs. For both breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperform all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus.

The antibody response magnitude and kinetics may impact clinical severity, serological diagnosis and long-term protection of COVID-19, which may play a role in why children experience lower morbidity. We therefore tested samples from 122 children in Hong Kong with symptomatic (n = 78) and asymptomatic (n = 44) SARS-CoV-2 infections up to 200 days post infection, relative to 71 infected adults (symptomatic n = 61, and asymptomatic n = 10), and negative controls (n = 48). We assessed serum IgG antibodies to a 14-wide antigen panel of structural and accessory proteins by Luciferase Immuno-Precipitation System (LIPS) assay and circulating cytokines. Infected children have lower levels of Spike, Membrane, ORF3a, ORF7a, ORF7b antibodies, comparable ORF8 and elevated E-specific antibodies than adults. Combination of two unique antibody targets, ORF3d and ORF8, can accurately discriminate SARS-CoV-2 infection in children. Principal component analysis reveals distinct pediatric serological signatures, and the highest contribution to variance from adults are antibody responses to non-structural proteins ORF3d, NSP1, ORF3a and ORF8. From a diverse panel of cytokines that can modulate immune priming and relative inflammation, IL-8, MCP-1 and IL-6 correlate with the magnitude of pediatric antibody specificity and severity. Antibodies to SARS-CoV-2 internal proteins may become an important sero surveillance tool of infection with the roll-out of vaccines in the pediatric population.

Real-world data are often multifaceted and can be meaningfully clustered in more than one way. There is a growing interest in obtaining multiple partitions of data. In previous work we learnt from data a latent tree model (LTM) that contains multiple latent variables (Chen et al. 2012). Each latent variable represents a soft partition of data and hence multiple partitions result in. The LTM approach can, through model selection, automatically determine how many partitions there should be, what attributes define each partition, and how many clusters there should be for each partition. It has been shown to yield rich and meaningful clustering results. Our previous algorithm EAST for learning LTMs is only efficient enough to handle data sets with dozens of attributes. This paper proposes an algorithm called BI that can deal with data sets with hundreds of attributes. We empirically compare BI with EAST and other more efficient LTM learning algorithms, and show that BI outperforms its competitors on data sets with hundreds of attributes. In terms of clustering results, BI compares favorably with alternative methods that are not based on LTMs.

Interleukin-17 (IL-17), a member of the IL-17 cytokine family, plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung. Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections, little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection. In this study, we show that H5N1-infected IL-17 knockout (KO) mice exhibit markedly increased weight loss, more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls. Moreover, the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection, which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice. Consistent with this observation, B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture. Taken together, these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.

The use of Xylocaine spray has been the common practice in many endoscopy centers, but scientific evidence is not conclusive on its superiority over other forms of topical anesthesia. This study aimed to compare the effectiveness of Xylocaine spray as a topical pharyngeal anesthesia for upper endoscopy and that of anesthetic lozenges with a characteristic flavor. A randomized placebo-controlled trial was performed in a single endoscopy center. For this study, 191 consecutive patients ages 18 to 70 undergoing outpatient esophagogastroduodenoscopy were randomized before the procedure into either a spray group (10% Xylocaine pump spray plus plain Strepsils) or a lozenge group (Strepsils Dual Action anesthetic lozenge plus distilled water spray). The primary outcome was the patient tolerance score, calculated according to the taste of the anesthetic agent, the intensity of numbness, the amount of cough or gag, and the degree of discomfort at esophageal intubation. The secondary outcomes included difficulty of esophageal intubation and the patients’ and endoscopists’ satisfaction score for the procedure. Randomization assigned 97 patients to the lozenge group and 94 patients to the spray group. The demographic data were similar in the two groups. The spray group had a significantly higher patient tolerance score, a greater intensity of numbness, less gag reflex, and less discomfort than the lozenge group. The lozenge group had a better taste than the spray group. The difficulty of esophageal intubation and the patients’ and endoscopists’ satisfaction were comparable between the two groups. Topical Xylocaine spray is superior to the flavored anesthetic lozenge as a topical pharyngeal anesthesia in unsedated esophagogastroduodenoscopy.

Our aging population is growing in size and diversity. To integrate different views on aging and make explicit the role of culture as a contextual factor, we modified Knight’s (Psychotherapy with older adults, 2004) Contextual, Cohort-based, Maturity, Specific Challenge (CCMSC) model of psychotherapy with older adults into the Contextual Adult Lifespan Theory for Adapting Psychotherapy (CALTAP). This article describes various components of the CALTAP, which serves as a meta-theoretical framework in guiding an integrated psychotherapy approach for the aging population. The interaction between environmental factors like cohort differences and socio-cultural contexts and individual factors such as maturation and age-related specific challenges not only shapes the experience and presentation of older adults in clinical settings, but also highlights special considerations in adapting psychotherapy for older adults.

The explicit formula for the effective dielectric constant of binary 0-3 composites (Poon and Shin, J. Mat. Sc. 39 (2004) 1277–1281) is extended into two explicit formulas for the prediction of the elastic properties of macroscopically isotropic 0-3 composites. By combining them with the explicit effective dielectric formula into a calculation scheme (Wong et al., J. Appl. Phys. 90 (2001) 4690), we obtained two new explicit formulas for the prediction of the d 31 and d 33 values for binary 0-3 piezoelectric composites. These two explicit formulas are applicable even when the inclusion volume fraction is high. Comparing with existing experimental data, they are found to fit more favorably than those predicted by Wong et al. and others. Also, being explicit makes these formulas much easier to be embedded into other effective property calculations for binary 0-3 composite materials.

The transcription factor upstream stimulatory factor 1 (USF1) regulates the expression of genes involved in glucose and lipid metabolism and has been associated with familial combined hyperlipidaemia. USF1 is located on chromosome 1q22-23, a region with evidence for linkage to type 2 diabetes and various traits of the metabolic syndrome in Chinese and other populations. The aim of this study was to investigate the linkage and association of USF1 with type 2 diabetes and the metabolic syndrome in Chinese individuals.We genotyped three haplotype-tagging single nucleotide polymorphisms (SNPs) (rs3737787, rs2516841 and rs2516839) at USF1 in three samples of the Hong Kong Chinese population, including members of 179 families from the Hong Kong Family Diabetes Study, 1,383 hospital cases with type 2 diabetes and/or the metabolic syndrome and 454 normal control subjects.We found significant association of individual polymorphisms and haplotypes with type 2 diabetes and/or metabolic syndrome-related traits in the family samples using either family-based or unrelated normal control subjects. However, these variants could not explain much of the evidence for linkage in this region. Moreover, they were not associated with type 2 diabetes and/or the metabolic syndrome in the hospital cases.The results are consistent with the hypothesis that variation at USF1 contributes to the risk of type 2 diabetes and the metabolic syndrome in families with strong evidence for linkage in the chromosome 1q region. However, they provide little support for USF1 as the susceptibility locus that generates the observed evidence for linkage at 1q21-25 for type 2 diabetes and/or the metabolic syndrome, and USF1 does not appear to have a major contribution to these phenotypes in the general Chinese population.

The single spherical cell model of F. J. Guild et al. (J. Mater. Sci. Lett. 13 (1994) 10) is extended to take into account the statistical spatial distribution of the inclusions in particulate-filled composite materials. Using this model, the elastic properties of a glass-bead filled epoxy composite material were calculated. When compared with the single spherical cell model, we found that the statistical spherical cell model gave predictions consistently closer to the experimental values for both the Young's modulus and the Poisson's ratio.

Angioedema of the oropharynx and hypopharynx due to oral angiotensin-converting enzyme (ACE) inhibitors is a potentially life-threatening event and has not been well described in the radiology literature. A retrospective review of the clinical and radiologic findings in three patients with angioedema due to ACE inhibitor use was performed.