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11 May 2021

First Participants Vaccinated In HKU Trial To Test COVID-19 Vaccines In Healthy Adolescents

PRESS RELEASE
 
Investigators of the Department of Paediatrics and Adolescent Medicine and the School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, are now launching the COVID-19 Vaccination in Adolescents (COVA) study. 300 healthy adolescents aged 11 years or above and their parents will be offered one of the COVID-19 vaccines available in Hong Kong of their choosing. The reactogenicity and immunogenicity profile of the vaccines will be compared. The first participants have just received dose 1 of their Fosun Pharma/BioNTech BNT162b2 vaccine.
 
The COVID-19 pandemic has caused more than 100 million cases and 3 million deaths globally, and over 10,000 cases in Hong Kong. The virus may cause long COVID and multisystem inflammatory syndrome in children. Some emerging virus variants have also been found to be more infectious to teenagers. Children and adolescents under 20 years old are contagious, and infected children may spread the virus to their grandparents. The prolonged suspension of classes and social distancing have also had a negative impact on students. Therefore, children and adolescents urgently need to be immunized against COVID-19.
 
COVA will recruit 300 healthy adolescents aged 11 years or above and their parents. At the moment, the families will be offered to receive the BioNTech/Fosun BNT162b2 or SinoVac's CoronaVac. Each family can freely choose the vaccine they receive, given each family member receives the same vaccine. Participants will report adverse reactions and other adverse events following immunization, and be followed up for immunogenicity assessments and vaccine breakthrough COVID-19 over a period of 3 years. Participants are covered by the Hong Kong government’s COVID-19 vaccine indemnity fund. Recruitment is ongoing, and those interested may sign up at https://paed.hku.hk/registration/cova/ or call or WhatsApp the Department of Paediatrics and Adolescent Medicine at 5944 5961 for more details. 
 
Timely local data on the reactogenicity and immunogenicity of COVID-19 vaccines in adolescents will inform the public and the government whether the vaccines should be given to adolescents, and allow complete school reopening as soon as possible.
 
About the research team
The COVA investigators include Professor Yu-Lung Lau, Doris Zimmern Professor in Community Child Health, Chair Professor of Paediatrics, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Malik Peiris, Tam Wah Ching Professor in Medical Science, Chair Professor of Virology, Centre for Immunology & Infection, Institut Pasteur and School of Public Health, HKUMed, Professor Wing-hang Leung, Head of Department and Clinical Professor, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Wenwei Tu, Antony and Nina Chan Professor in Paediatric Immunology and Professor, Department of Paediatrics and Adolescent Medicine, HKUMed, Professor Roberto Bruzzone, Visiting Professor, School of Public Health, Centre for Immunology & Infection, HKUMed, Professor Leo Poon, Professor, School of Public Health, HKUMed; also from the Department of Paediatrics and Adolescent Medicine, HKUMed: Dr Patrick Ip, Clinical Associate Professor, Dr Pamela Lee Pui-Wah, Clinical Associate Professor, Dr Jaime Rosa Duque, Clinical Assistant Professor, Dr Gilbert T Chua, Clinical Assistant Professor, Dr Wilfred Hing-sang Wong, Senior IT Manager, Ms Sau Man Chan, Research Nurse, Dr Kai N Cheong, Honorary Clinical Assistant Professor, and Mr Daniel Leung, MBBS/PhD student.
 
About the Department of Paediatrics and Adolescent Medicine, HKU 
The Department of Paediatrics and Adolescent Medicine is a pre-eminent international paediatrics department in Asia striving for the health and well-being of children and youth. We endeavour to provide high-quality children-centred health care services to the community; produce graduates, postgraduates and paediatricians of distinction, committed to lifelong learning, integrity and professionalism; engage in both basic and clinical research of innovation and high-impact, within and across disciplines; and form alliances and partnerships in order to achieve our vision and mission. 
 
About the Centre for Immunology & Infection (C2i)
The C2i is the fruit of a long-standing partnership of more than 20 years between the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) and the Institut Pasteur, two major institutions combining their expertise to establish this centre of excellence. C2i, adopts innovative strategies to identify and contain emerging infectious diseases and transform Hong Kong and the Greater Bay Area into a global hub of knowledge and research.
 
The Centre for Immunology & Infection's work is centered around four major research programs to face public health challenges and make Hong Kong a global center of excellence for precision medicine population strategies and innovative interventions targeting emerging infectious diseases. They aim to characterise immune responses to infectious agents and their components in a healthy Asian population and develop new vaccine platforms for influenza, new strategies for mosquito-borne viruses and new treatments for lethal respiratory virus infections. The C2i is led by Professor Malik Peiris (Managing Director) and Professor Roberto Bruzzone (Co-director).
 
The study is funded by the Food and Health Bureau and private donations.
 
Media enquiries
Department of Paediatrics and Adolescent Medicine, HKU
Daniel Leung (Tel: 2255 4538 | Email: dan.leung@hku.hk)
 
 

Photo of COVA study team in the community vaccination centre on May 8 2021. The COVA
study is supported by experienced paediatricians, nursing staff, clinical research assistants
and medical students at the vaccination centre.
 
 

27 Apr 2021

Coronavirus Seroprevalence Among Villagers Exposed To Bats In Thailand

Hein Min Tun signed with colleagues from the Center of Excellence for Emerging and Re‐emerging Infectious Diseases in Animals of the Chulalongkorn University, Bangkok, a paper on a serological survey of human coronavirus antibodies among villagers in 10 provinces of Thailand that was conducted between 2016–2018 in the Wiley Online Library.
 
They showed that 10.44% (38/364) of the villagers had developed antibodies against human coronaviruses.
 
The odds ratio for coronavirus positivity in the villagers in the central region who were exposed to bats was 4.75 (95% CI 1.04–21.70) compared to that for the non‐exposed villagers.
 
Their results showed that 62.36% (227/364) of the villagers had been exposed to bats at least once in the past six months and that low monthly family income was statistically significant in increasing the risk for coronavirus seropositivity among the villagers.
 
Abstract
A serological survey of human coronavirus antibodies among villagers in 10 provinces of Thailand was conducted during 2016–2018. Serum samples (n = 364) were collected from participants from the villages and tested for coronavirus antibodies using a human coronavirus IgG ELISA kit. Our results showed that 10.44% (38/364; 21 males and 17 females) of the villagers had antibodies against human coronaviruses. The odds ratio for coronavirus positivity in the villagers in the central region who were exposed to bats was 4.75, 95% CI 1.04–21.70, when compared to that in the non‐exposed villagers. The sociodemographics, knowledge, attitudes and practices (KAP) of the villagers were also recorded and analysed by using a quantitative structured questionnaire. Our results showed that 62.36% (227/364) of the villagers had been exposed to bats at least once in the past six months. Low monthly family income was statistically significant in increasing the risk for coronavirus seropositivity among the villagers (OR 2.91, 95% CI 1.13–7.49). In‐depth interviews among the coronavirus‐positive participants (n = 30) showed that cultural context, local norms and beliefs could influence to bat exposure activities. In conclusion, our results provide baseline information on human coronavirus antibodies and KAP regarding to bat exposure among villagers in Thailand.
 
 
Map of study provinces in Thailand and percentages of CoV seropositivity among villagers.

20 Apr 2021

Understanding the microbial composition of the respiratory tract in hospitalized Covid-19 patients

Hein Min Tun’s team, in collaboration with colleagues from Denmark, Guangzhou, and Shenzhen among others, have studied the characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients. This study published in Nature’s Cell Discovery focuses on the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19.

From the identification of distinct signatures of microbial dysbiosis among severely ill Covid-19 patients, their work highlights the need for adapted detection and tracking strategies to prevent the spread of antimicrobial resistance and improve the clinical outcomes of hospitalized patients.

>>> Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

 

a Presence/absence profile of nonviral microbial genera in mild and severe cases. Orange, mild; brick red, severe. Only common genera detected in over 60% of patients in the mild cases (n > 4) or severe cases (n > 7) are shown. b Bar plot showing the relative expression levels of nonviral microbes in all respiratory specimens of mild (orange, n = 7) and severe cases (brick red, n = 40). c Relative expression levels of selected genera differing between mild and severe cases. The bar chart and black error bars denote the mean and standard error values of expression levels in mild (orange) and severe (brick red) cases for each genus. ***P < 0.001; **P < 0.01; *P < 0.05; Wilcoxon rank-sum test. For patients with multiple respiratory specimens (all were severe cases), the presence of a given genus is considered when at least one sample from this patient was positive for the taxon (relative abundance > 0) (a), and the comparisons between relative expression levels of selected genera are conducted across all collected respiratory samples between mild and severe cases (c).

19 Apr 2021

Multi-platform omics analysis reveals molecular signature for COVID-19 pathogenesis, prognosis and drug target discovery

Hein Min Tun and colleagues published in Nature's Signal Transduction and Targeted Therapy about a multi-platform omics analysis to get a depper insight about potential strategies for severe COVID-19 patient treatment.

>>> Multi-platform omics analysis reveals molecular signature for COVID-19 pathogenesis, prognosis and drug target discovery

Abstract:
Disease progression prediction and therapeutic drug target discovery for Coronavirus disease 2019 (COVID-19) are particularly important, as there is still no effective strategy for severe COVID-19 patient treatment. Herein, we performed multi-platform omics analysis of serial plasma and urine samples collected from patients during the course of COVID-19. Integrative analyses of these omics data revealed several potential therapeutic targets, such as ANXA1 and CLEC3B. Molecular changes in plasma indicated dysregulation of macrophage and suppression of T cell functions in severe patients compared to those in non-severe patients. Further, we chose 25 important molecular signatures as potential biomarkers for the prediction of disease severity. The prediction power was validated using corresponding urine samples and plasma samples from new COVID-19 patient cohort, with AUC reached to 0.904 and 0.988, respectively. In conclusion, our omics data proposed not only potential therapeutic targets, but also biomarkers for understanding the pathogenesis of severe COVID-19.

 

Overview of samples for multi-omics study. a Multi-omics analysis design with three datasets. The training dataset combined with severe, non-severe, and healthy controls, proteins, lipids, and amino acids were quantified in plasma and used for biomarker discovery, using random forest. The validation cohort 1 contained ten plasma samples from from non-severe and five severe patients, 25 molecules were targeted quantified for prediction evaluation. The validation cohort 2 contained urine samples corresponding to plasma samples in the training dataset, and prediction precision was further evaluated using targeted quantification. b Sample information of COVID-19 patients in the training dataset with time annotation from onset of disease to admission or from admission to discharge

25 Mar 2021

Role Of Gut Microbiota In Travel-Related Acquisition Of Extended Spectrum β-lactamase-Producing Enterobacteriaceae

What a week for the Tun Lab! 
 
After their publication in Gastroenterology and the award they received at the 2021 Inventions Geneva Evaluation Days for the “Innovative Sewage Testing Tool for SARS-CoV-2” project, Hein Min Tun and PhD student Ye Peng publish in the Journal of Travel Medicine (Oxford Academic) about the role of gut microbiota in the acquisition of antimicrobial resistant bacteria during international travels. 
 
 
Abstract
Background
International travel could facilitate the spread of antimicrobial-resistant bacteria including extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). Previous studies, which attempted to understand the role of gut microbiota in the acquisition of antimicrobial resistant bacteria during international travels, are limited to western travellers.


Methods
We established a prospective cohort of 90 Hong Kong travellers to investigate gut microbiota determinants and associated risk factors for the acquisition of ESBL-E. Baseline characteristics and travel-associated risk factors were gathered through questionnaires. Faecal samples were collected in 3-4 days before and after travel. Antimicrobial susceptibility of ESBL-E isolates was tested, and gut microbiota were profiled by 16S rDNA amplicon sequencing. Non-parametric tests were used to detect potential associations, and logistic regression models were used to quantify the associations. Random forest models were constructed to identify microbial predictors for ESBL-E acquisition.


Results
In total, 49 (54.4%) participants were tested negative for ESBL-E colonization before travel and were followed up after travel. A total of 60 ESBL-E isolates were cultured from 20 (40.8%) participants. Having low Actinobacteria richness and low abundance of short-chain fatty acid-producing bacteria in the gut microbiota before travel increased the risk of acquiring ESBL-E and the risk can be further exacerbated by eating raw seafood during travel. Besides, post-travel ESBL-E positive participants had increased abundances of several opportunistic pathogens such as Staphylococcus, Enterococcus, Escherichia/Shigella and Klebsiella. The random forest model integrating pre-travel microbiota and the identified travel-related risk factor could predict ESBL-E acquisition with an area under the curve of 75.4% (95% confidence interval: 57.9–93.0%).


Conclusions
In this study, we identified both travel-related risk factors and microbiota predictors for the risk of ESBL-E acquisition. Our results provide foundational knowledge for future developments of microbiota-based interventions to prevent ESBL-E acquisition during international travels.
 

24 Mar 2021

Ethnicity Associations With Food Sensitization Are Mediated By Gut Microbiota Development In The First Year Of Life

New publication from the Tun Lab! 
Dr Hein Min Tun, Ye Peng (PhD student) and team published in Gastroenterology about the relationship between food sensitization and the development of gut microbiota during the first year of life, with fellow colleagues from University of Alberta and University of Toronto, Canada, within the CHILD Cohort Study, a robust Canadian research platform to understand development of disease so it can be predicted, prevented or better treated.
 
 
 
Abstract
Background and aims: Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children.
 
Methods: In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years was determined. Ethnicity and early life exposures influencing microbiota trajectories were initially examined, and post hoc analyses were conducted.
 
Results: Four identified developmental trajectories of gut microbiota were shaped by birth mode and varying by ethnicity. The trajectory with persistently-low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly peanut at age 3 years by 3-fold (adjusted OR, 2.82; 95% CI, 1.13-7.01); a much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR, 7.87; 95% CI, 2.75-22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent C. difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization.
 
Conclusions: This study documented an association between persistently-low gut Bacteroides abundance throughout infancy and sensitization to peanut in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.
 

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