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03 Aug 2020

Lessons Learned From The SARS Pandemic, A Review On The Topic By Prof. Malik Peiris And Prof. Leo Poon

In a new publication, Prof. Malik Peiris, HKU School of Public Health and former co-director the HKU-Pasteur Research Pole, and his successor Prof. Leo Poon, reflect on what the SARS 2003 pandemic in Hong Kong have enabled scientists to understand about the cause of these types of coronaviruses.
 
Severe acute respiratory syndrome (SARS) was the first major global public health crisis of the 21st century. In March 2003, scientists reported to the World Health Organization (WHO) the discovery of a novel coronavirus (CoV) responsible for this newly emerged disease. SARS first emerged in Guangdong, China in November 2002, leading to major outbreaks in the Provincial capital Guangzhou in January. HKU-Pasteur first heard about these outbreaks in mid-February 2003. Hong Kong set up enhanced surveillance for all patients with severe pneumonia of unknown aetiology in Hong Kong, especially those with a travel history to Guangdong. 
 
The two researchers’ first investigation for known respiratory pathogens proved negative. They then started to look more broadly for unusual viruses, including attempting virus culture using a range of cell lines not normally used for respiratory viruses, broad-range PCR/RT-PCR, random primer RT-PCR methods as well as electron microscopy of a lung biopsy from a suspected patient. By March 17, 2003, they began to see subtle changes in FRhk 4 monkey kidney cells inoculated with specimens from two suspected patients. By electron microscopy, they could see virus particles within these cells and we then used fixed infected cells to demonstrate antibody responses in paired sera from a number of suspected SARS patients but not in controls. Using random RT-PCR, they were able to identify the virus as a novel coronavirus. The initial short RNA sequence of 646 nucleotides obtained from the random RT-PCR rapidly allowed the development of RT-PCR assays for detecting SARS patients. 
 
All these findings were shared in real-time via daily teleconferences organized by the WHO to link up laboratories working on this outbreak. Two other laboratories within the network (Centers for Disease Control and Prevention, USA and Bernhard Nocht Institute for Tropical Medicine, Hamburg) reported similar findings from other SARS patients but others were still arguing for other aetiologies (e.g., human metapneumovirus). Sharing of data within the WHO network allowed a rapid consensus that the novel coronavirus was indeed the cause of SARS.
 
 

31 Jul 2020

Institut Pasteur Transverse Research Programs: HKU-Pasteur To Work On The Relationship Between Stem Cells And Infectious Diseases

Flu is a contagious infectious disease caused by the influenza virus. Influenza A and B viruses circulate and cause seasonal epidemics. Each year about 3-5 million individuals develop a severe illness, causing 290 000 to 600 000 deaths. Flu is an infection of the respiratory tract characterized by a sudden onset of symptoms such as fever, cough, headache, muscle and joint pain. Most people recover within a week, but influenza can cause severe illness or death especially in high risk population, such as pregnant women, elderly, young children, individual with chronic diseases and health care workers. 
 
Decline of independence after hospitalization has been reported in the elderly, as well as in specialized residence. This poses a number of issues, including an ever-increasing cost of national health care budgets. So far, researchers are mainly focused on respiratory complications leading to death, but few studies are addressing the causes and the consequences of the associated symptoms
 
Between 2015 and 2018, Barbara Gayraud-Morel, from the unit of Stem Cells and Development (Institut Pasteur Paris) directed by Shahragim Tajbakhsh, had the opportunity to establish a fruitful collaboration with HKU-Pasteur, laying the foundations for this project under the Institut Pasteur Transverse Research Programs.
 
This partnership will unite their expertise on skeletal muscle research, stem cell biology and infectious diseases to investigate the consequences of influenza viral infection at a site where the biology of tissue stem cells has been investigated, notably in skeletal muscles. The observation that inflammatory molecules reach skeletal muscles led them to investigate the stem cell or pathogen driven systemic inflammation interactions which has so far remained unexplored. The compelling preliminary data gathered by the team led them to find that skeletal muscle stem cells respond to the systemic inflammation when there is an intranasal infection by the influenza virus. This opens a new field of research that exposes physiological response of tissues and organs to pathogens.
 
The characterisation of the molecular basis and functionality of this phenomenon will have a significant impact on human health by revealing an appreciated role of stem cells in symptoms associated with systemic inflammation during and after infection. This new field of investigation will inevitably be extended to other tissues and organs, for example, to evaluate if nerve, skin or intestinal stem cells are affected by systemic inflammation and result in altered function. With this new project, the team aims to understand the signalling molecules and mechanisms acting on muscle stem cells remotely from the site of infection, through the characterization of the biological response adopted by the muscle stem cells in this context of viral inflammation. 
 
They will also explore if their observations on muscle stem cells in influenza-mediated inflammation could be a landmark of a more general stem cell response to acute inflammation in other contexts. To this end, this project associates the Centre for Translational Science Unit of Fabrice Chrétien (Institut Pasteur Paris), which has the expertise in another distinct systemic infection model, sepsis, in order to explore and compare the two paradigms, one related to viral response, and the other, a polybacterial infection. 
 
This project, which is the result of synergistic expertise within the Pasteur network, opens a new field of investigation on the relationship between stem cells and infectious diseases. Strong preliminary data have paved the way for us to explore this area further and position this topic at the forefront of international research. 
 

29 Jul 2020

COVID-19: Even Mild Cases Develop A Robust, Neutralizing Antibody Response

Chris Mok and his team worked on the development of the immune response in COVID-19 patients in collaboration with Dr Jincun Zhao from the State Key Laboratory of Respiratory Disease of Guangzhou Medical University. During their research, they found that even mild cases have a robust, neutralizing antibody response.

As of late July, the World Health Organization (WHO) has reported more than 15 Million cases of COVID-19 worldwide, including more than 640,000 deaths, and still little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response to SARS-COV-2.

In this publication, in order to monitor viral shedding and antibody responses in patients with severe and mild disease in different tissues, the authors recruited two groups of RT-PCR confirmed COVID-19 patients, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards.

They found that COVID-19 patients with different severity of disease showed different patterns of viral shedding and antibody responses. Severe patients had more prolonged viral shedding in a variety of tissues than mildly ill patients. SARS-CoV-2-specific antibodies were found in tissues outside the respiratory tract in severe patients. Detection of antibody responses in urine and other body fluids could be used as a marker to determine disease severity. 

Interestingly, by using plasma from SARS, MERS and COVID-19 patients, strong cross-reactivities were detected between SARS-CoV-2 and SARS-CoV, but not MERS-CoV which is an important information for differential diagnosis in Middle East countries. 

More importantly, antibodies against N or S protein were correlated with neutralizing antibody titers which may be useful when screening convalescent plasma for passive transfusion therapy.

In summary, this study provides comprehensive information on kinetics, tissue distribution, cross-reactivities and neutralization of antibody responses in COVID-19 patients, and will improve our understanding of humoral immune response in human after SARS-CoV-2 infection as well as shedding light on diagnosis, prognosis, convalescent plasma transfusion therapy and epidemiology studies of SARS-CoV-2 infection in human.

Their findings are published by the Journal of Clinical Investigation:

>>> Kinetics Of Viral Load And AntibodyResponse In Relation To COVID-19 Severity

21 Jul 2020

Chris Mok’s Collaborative Project With Institut Pasteur Tunis Selected By The Institut Pasteur International Covid-19 Task Force

Since January 2020, the Institut Pasteur Covid-19 Task Force and the Institut Pasteur International Network have been extremely active worldwide in responding with science to the pandemic caused by the SARS-CoV-2 coronavirus. 

The joint project developed by Chris Mok’s team at the HKU-Pasteur Research Pole and by the Institut Pasteur Tunis, Tunisia, will be funded by the Covid-19 Task Force as part of the second round of projects selection. 

In this framework, the project “EASI: ELISA Assays development for SARS-COV2” will focus on the development of diagnostic tools. “ELISA” is a widely established technology to detect the presence of antigens in samples.

Screening with this ELISA assay is a reliable approach for large-scale sero-epidemiological studies, which are crucial to assess infection attack rates in the population and to accurately define disease severity and herd immunity.

Scientific collaboration in times of global pandemic is crucial to capitalize on various countries and laboratories’ expertise in order to develop groundbreaking projects. 

 

20 Jul 2020

New Groundbreaking Findings With A Coating That Can Kill SARS-CoV-2

The breakthrough study, recently published in ACS Applied Materials & Interfaces, has been conducted by Dr Alex Chin, investigator in Professor Leo Poon’s team, Co-Director of the HKU-Pasteur Research Pole, in collaboration with Professor William Ducker of the Department of Engineering at Virginia Tech, that developed the technology.

The joint research team has previously showed that SARS-CoV-2, the virus that causes COVID-19, can retain on smooth surface such as stainless steel, glass, and plastic up to 2 to 4 days. Such contaminated surfaces can facilitate fomite transmission of SARS-CoV-2. As a result of this recent collaboration, they have demonstrated a surface coating containing cuprous oxide (Cu2O) bound with polyurethane can inactivate SARS-CoV-2 by more than 99.9% in 1 hour. This surface coating can be easily applied to common materials such as metals and glass to reduce the risk of COVID-19 transmission via indirect contact.

The next step now according to the researchers will be to attract funding in order to mass-produce the coating.

08 Jul 2020

Living Close To Natural Green Space Benefits Gut Bacteria Of Urban, Formula-fed Infants

This is the first study showing that formula-fed babies’ gut microbiome is comparable to gut microbiome of breastfed babies living near natural environments. 
 
Living close to natural green space can mitigate some of the changes in infant gut bacteria associated with formula feeding, according to a new research published in the journal Environment International and co-led by Hein Tun, group leader at HKU-Pasteur Research Pole and Anita Koyzrskyj, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
 
Although we consider maternal breastmilk is nature’s gift, not every infant can be breastfed. This is one of the first pieces of evidence for a nature-related intervention that could possibly help promote healthy gut microbial composition in infants not breastfed,” said Hein Tun, assistant professor of public health, who studies the developmental gut microbiota in infants and its role in developing allergies and metabolic diseases in children. 
 
In this study, the researchers examined fecal microbiota of 355 four-month-old infants in Edmonton who are part of the CHILD Cohort Study. Their postal codes were then cross-referenced with the City of Edmonton’s urban Primary Land and Vegetation Inventory (uPLVI), which maps natural green spaces in the city, including natural forest, grasslands, wetlands, lakes, rivers and ravines. 
 
We found that the infants who lived within 500 metres of a natural environment were less likely to have higher diversity in their gut bacteria,” said Anita Koyzrskyj. “It may seem counterintuitive, but a young breastfed infant has lower gut microbial diversity than a formula-fed infant because formula feeding increases the number of different gut bacteria.
 
Although the greatest association was found for formula-fed infants living in a home with a pet, the exact mechanism is not yet understood. The authors hypothesize that families who walk their dog may use natural areas more often, or perhaps pets bring healthy bacteria into the home on their fur. 
  
Our previous study indicated that having furry pets at home could introduce beneficial microbes to babies and we know that introducing a pet into the home does change the types of microbes in household dust.” Tun pointed out.
 
WHO’s recommendation for exclusive breastfeeding is for the first six months of life. In Hong Kong, the rate is still as low as one-fourth of the infant population. More local research is needed to examine the health consequences,” Tun said.  “Even most HK people live in high-rise buildings, if you frequently visit local country parks, it could give you similar benefits.”  
 
The study’s senior authors often receive emails from mothers who are unable to practice breastfeeding and are concerned about their children’s futures. Based on the study’s results, they will now advise them to take their babies out to natural areas and consider getting a pet.
 
Summer photo created by wirestock - Freepik

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