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COMMENTARY: Vaccines can be less effective for seniors. What does this mean for COVID-19? – Global News

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As the global spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) — the cause of COVID-19 — continues, we learn more about the effects of this new virus.

For many respiratory pathogens, including influenza viruses and respiratory syncytial viruses, the elderly experience the most severe forms of disease and the highest death rates. For example, for every 10,000 Americans between 18 and 49 years old, only 0.4 people die from the annual flu. That number increases to 5.9 people per 10,000 for those aged 65-74 years, and 47.5 people for those over 74 years old. However, most of these diseases can also have a predilection for causing severe disease in the very young.

In this respect, COVID-19 is very different. Data from relatively early in the COVID-19 pandemic showed a dramatic difference in the rates of age-associated deaths, with a case fatality rate of 4.5 per cent for patients ages 60 and older versus only 1.4 per cent for those under 60 years old, with those under 30 years ranging from zero to 0.19 per cent.

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READ MORE: Early results find U.K. coronavirus vaccine ‘safe and induces an immune reaction’

Immunosenescence

We are immunologists with research programs devoted to developing vaccines. With COVID-19 placing a spotlight on the elderly as the age demographic most in need of a vaccine, we have felt compelled to evaluate how well scientists are doing at tailoring immunization strategies for this population.

Our conclusion is that vaccinologists, ourselves included, have largely failed to focus their research on tailoring vaccine technologies to induce robust immune responses in the elderly.

A critical factor that makes the elderly more susceptible to infectious diseases is what immunologists call “immunosenescence”: the decline in the immune system’s functionality as people age. This is also associated with an increase in the incidence of inflammatory diseases, because an elderly body tends to be in a state of chronic low-grade inflammation. This “inflamm-aging” is one reason why older people have tendencies to develop more severe forms of respiratory diseases.

The key problem with SARS-CoV-2 infection is inflammation in the respiratory tract, which can be exacerbated in individuals predisposed towards potent inflammatory responses.

Immunosenescence also results in diminished responses to vaccination. Indeed, annual flu vaccines are notoriously less effective in the elderly. This phenomenon is very important in the context of the massive efforts and funds being invested worldwide into the ultra-rapid development of vaccines for COVID-19.

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The fact that elderly people do not respond well to immunizations has largely been ignored in most discussions of COVID-19 vaccines, despite this being the group in greatest need. Most of the scientific community’s experience with vaccine development for any disease has been focused on vaccinating the relatively young.






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Young mice and elderly humans

Here is an interesting exercise for people reading this article: find as many original research articles as you can on the topic of vaccine development that have used animal models (it could be for any disease). Then look in the subsection of the “materials and methods” section and check the age of the animals. We were shocked by what we found.

Mice are the most common animals used in preclinical vaccine research and the overwhelming majority of these are 12 weeks old or younger. This is equivalent to people 20 years old and younger. It is comparatively much rarer for studies to use immunosenescent mice that are at least 18 months old and equivalent to an elderly human.

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Translational studies that take promising preclinical discoveries and move them towards clinical trials often use non-human primates such as Rhesus macaques. In the majority of cases these are around three to six years old, which is equivalent to an adolescent or young-adult human. The same trend applies to all other animals used in vaccine research.

Early-phase clinical trials focus on safety, not efficacy of vaccines. Therefore, far too many vaccines never get tested in the context of aged immune systems until Phase 2 and 3 clinical trials. The time to find out that a vaccine does not work well in the context of immunosenescence is not at this extremely late stage, when it is too late to fix the problem. This testing should begin in the preclinical phase where an iterative process can be followed to tailor a vaccine for a senescent immune system.

A C57BL/6 mouse. (Shutterstock)

Interestingly, many commercial suppliers of animals that are purpose-bred for research do not have adequate inventories of old animals. Of concern, most old mice that are readily available are of the C57BL/6 strain. This is the most common strain used in research, and is known to have an immune system with a strong bias towards effective responses against viruses.

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Intriguingly, aged mice experience a more severe form of SARS after infection, akin to elderly humans. The excessive use of young mice with immune systems that are optimal for antiviral responses, and that experience less severe disease, could bias results in a way that overestimates the potential of vaccines to perform well in the elderly.

READ MORE: U.S. inks coronavirus trial vaccine deal with Pfizer for first 100 million doses

Developing vaccines for a key demographic

People age 65 and over suffer the most severe cases of COVID-19 and have the highest associated mortality rate. If the goal is to have COVID-19 vaccines ready for public use by early 2021, the only ones that have a chance are those that are currently in clinical trials. It is likely that most of these did not undergo preclinical optimization for an elderly population, meaning these first-generation COVID-19 vaccines may perform poorly in the people that need them most.

For the COVID-19 pandemic, it is too late to go back and build these considerations into preclinical testing. However, it is imperative that researchers still in the preclinical phase incorporate head-to-head testing of their vaccine candidates in young versus aged animals and develop strategies to optimize them in the latter. This will help the world prepare for the next outbreak of a dangerous coronavirus.

For that matter, a focus on the elderly should be incorporated into other vaccine development programs, including those to treat cancers, which have the highest incidence in older people.

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There are viable strategies to improve the effectiveness of vaccines in older people, including changes in formulations, doses and routes of administration. However, it takes substantial time and appropriate animal models to conduct this research. It is possible that the elderly may need fundamentally different vaccination regimens than younger people.

Although a few researchers do conduct vaccine studies in old animals, considerations for the elderly need to be adopted by far more vaccinologists. This is of growing importance for countries with aging populations. This will mean changing the current philosophy of the field of vaccine development and incorporating age as a critical variable.

Byram W. Bridle, Associate Professor of Viral Immunology, Department of Pathobiology, University of Guelph and Shayan Sharif, Professor of Immunology and Associate Dean, Research and Graduate Studies, University of Guelph

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This article is republished from The Conversation under a Creative Commons licence. Read the original article.

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Telus prioritizing ‘most important customers,’ avoiding ‘unprofitable’ offers: CFO

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Telus Corp. says it is avoiding offering “unprofitable” discounts as fierce competition in the Canadian telecommunications sector shows no sign of slowing down.

The company said Friday it had fewer net new customers during its third quarter compared with the same time last year, as it copes with increasingly “aggressive marketing and promotional pricing” that is prompting more customers to switch providers.

Telus said it added 347,000 net new customers, down around 14.5 per cent compared with last year. The figure includes 130,000 mobile phone subscribers and 34,000 internet customers, down 30,000 and 3,000, respectively, year-over-year.

The company reported its mobile phone churn rate — a metric measuring subscribers who cancelled their services — was 1.09 per cent in the third quarter, up from 1.03 per cent in the third quarter of 2023. That included a postpaid mobile phone churn rate of 0.90 per cent in its latest quarter.

Telus said its focus is on customer retention through its “industry-leading service and network quality, along with successful promotions and bundled offerings.”

“The customers we have are the most important customers we can get,” said chief financial officer Doug French in an interview.

“We’ve, again, just continued to focus on what matters most to our customers, from a product and customer service perspective, while not loading unprofitable customers.”

Meanwhile, Telus reported its net income attributable to common shares more than doubled during its third quarter.

The telecommunications company said it earned $280 million, up 105.9 per cent from the same three-month period in 2023. Earnings per diluted share for the quarter ended Sept. 30 was 19 cents compared with nine cents a year earlier.

It reported adjusted net income was $413 million, up 10.7 per cent year-over-year from $373 million in the same quarter last year. Operating revenue and other income for the quarter was $5.1 billion, up 1.8 per cent from the previous year.

Mobile phone average revenue per user was $58.85 in the third quarter, a decrease of $2.09 or 3.4 per cent from a year ago. Telus said the drop was attributable to customers signing up for base rate plans with lower prices, along with a decline in overage and roaming revenues.

It said customers are increasingly adopting unlimited data and Canada-U.S. plans which provide higher and more stable ARPU on a monthly basis.

“In a tough operating environment and relative to peers, we view Q3 results that were in line to slightly better than forecast as the best of the bunch,” said RBC analyst Drew McReynolds in a note.

Scotiabank analyst Maher Yaghi added that “the telecom industry in Canada remains very challenging for all players, however, Telus has been able to face these pressures” and still deliver growth.

The Big 3 telecom providers — which also include Rogers Communications Inc. and BCE Inc. — have frequently stressed that the market has grown more competitive in recent years, especially after the closing of Quebecor Inc.’s purchase of Freedom Mobile in April 2023.

Hailed as a fourth national carrier, Quebecor has invested in enhancements to Freedom’s network while offering more affordable plans as part of a set of commitments it was mandated by Ottawa to agree to.

The cost of telephone services in September was down eight per cent compared with a year earlier, according to Statistics Canada’s most recent inflation report last month.

“I think competition has been and continues to be, I’d say, quite intense in Canada, and we’ve obviously had to just manage our business the way we see fit,” said French.

Asked how long that environment could last, he said that’s out of Telus’ hands.

“What I can control, though, is how we go to market and how we lead with our products,” he said.

“I think the conditions within the market will have to adjust accordingly over time. We’ve continued to focus on digitization, continued to bring our cost structure down to compete, irrespective of the price and the current market conditions.”

Still, Canada’s telecom regulator continues to warn providers about customers facing more charges on their cellphone and internet bills.

On Tuesday, CRTC vice-president of consumer, analytics and strategy Scott Hutton called on providers to ensure they clearly inform their customers of charges such as early cancellation fees.

That followed statements from the regulator in recent weeks cautioning against rising international roaming fees and “surprise” price increases being found on their bills.

Hutton said the CRTC plans to launch public consultations in the coming weeks that will focus “on ensuring that information is clear and consistent, making it easier to compare offers and switch services or providers.”

“The CRTC is concerned with recent trends, which suggest that Canadians may not be benefiting from the full protections of our codes,” he said.

“We will continue to monitor developments and will take further action if our codes are not being followed.”

French said any initiative to boost transparency is a step in the right direction.

“I can’t say we are perfect across the board, but what I can say is we are absolutely taking it under consideration and trying to be the best at communicating with our customers,” he said.

“I think everyone looking in the mirror would say there’s room for improvement.”

This report by The Canadian Press was first published Nov. 8, 2024.

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TC Energy cuts cost estimate for Southeast Gateway pipeline project in Mexico

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CALGARY – TC Energy Corp. has lowered the estimated cost of its Southeast Gateway pipeline project in Mexico.

It says it now expects the project to cost between US$3.9 billion and US$4.1 billion compared with its original estimate of US$4.5 billion.

The change came as the company reported a third-quarter profit attributable to common shareholders of C$1.46 billion or $1.40 per share compared with a loss of C$197 million or 19 cents per share in the same quarter last year.

Revenue for the quarter ended Sept. 30 totalled C$4.08 billion, up from C$3.94 billion in the third quarter of 2023.

TC Energy says its comparable earnings for its latest quarter amounted to C$1.03 per share compared with C$1.00 per share a year earlier.

The average analyst estimate had been for a profit of 95 cents per share, according to LSEG Data & Analytics.

This report by The Canadian Press was first published Nov. 7, 2024.

Companies in this story: (TSX:TRP)

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BCE reports Q3 loss on asset impairment charge, cuts revenue guidance

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BCE Inc. reported a loss in its latest quarter as it recorded $2.11 billion in asset impairment charges, mainly related to Bell Media’s TV and radio properties.

The company says its net loss attributable to common shareholders amounted to $1.24 billion or $1.36 per share for the quarter ended Sept. 30 compared with a profit of $640 million or 70 cents per share a year earlier.

On an adjusted basis, BCE says it earned 75 cents per share in its latest quarter compared with an adjusted profit of 81 cents per share in the same quarter last year.

“Bell’s results for the third quarter demonstrate that we are disciplined in our pursuit of profitable growth in an intensely competitive environment,” BCE chief executive Mirko Bibic said in a statement.

“Our focus this quarter, and throughout 2024, has been to attract higher-margin subscribers and reduce costs to help offset short-term revenue impacts from sustained competitive pricing pressures, slow economic growth and a media advertising market that is in transition.”

Operating revenue for the quarter totalled $5.97 billion, down from $6.08 billion in its third quarter of 2023.

BCE also said it now expects its revenue for 2024 to fall about 1.5 per cent compared with earlier guidance for an increase of zero to four per cent.

The company says the change comes as it faces lower-than-anticipated wireless product revenue and sustained pressure on wireless prices.

BCE added 33,111 net postpaid mobile phone subscribers, down 76.8 per cent from the same period last year, which was the company’s second-best performance on the metric since 2010.

It says the drop was driven by higher customer churn — a measure of subscribers who cancelled their service — amid greater competitive activity and promotional offer intensity. BCE’s monthly churn rate for the category was 1.28 per cent, up from 1.1 per cent during its previous third quarter.

The company also saw 11.6 per cent fewer gross subscriber activations “due to more targeted promotional offers and mobile device discounting compared to last year.”

Bell’s wireless mobile phone average revenue per user was $58.26, down 3.4 per cent from $60.28 in the third quarter of the prior year.

This report by The Canadian Press was first published Nov. 7, 2024.

Companies in this story: (TSX:BCE)

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