The steady increase in new cases of COVID-19 in Canada’s most populated provinces is a concerning trend, according to the country’s chief public health officer, as hospitals work to keep intensive care admissions manageable.
Dr. Theresa Tam said in a statement Monday that an average of 618 new cases have been reported daily in the last seven days, particularly in Quebec, Ontario, Alberta and British Columbia — 20 per cent higher than the previous week.
“We’re watching not just the numbers but the speed of ramp up and how widespread the cases are,” Tam said in an interview with CBC Radio’s The Current.
“If there’s a rapid rise over a short period of time, confined to a very specific location, what you’re worried about is stressing the public health system and the health system in those areas.”
Hospital and ICU admissions are a sign of concern since older groups generally have more serious outcomes from COVID-19, although people of any age can be affected and transmit the infection, she said.
WATCH | Early resurgence a concern, infectious disease specialist says:
‘I was really expecting to see more of a rise like this in October but it’s real and it’s happening now,’ said Dr. Isaac Bogoch, an infectious disease specialist. 0:36
Tam said her public health counterparts say the situation is currently “manageable.” But their jobs become more difficult if people aren’t doing their part to minimize their numbers of contacts and exposures should a case occur.
Dr. Kevin Smith, president and CEO of Toronto’s University Health Network, has said he’s “worried” because the number of patients with COVID-19 in intensive care has increased after some weeks of having no one hospitalized with the disease.
Cases are doubling in Canada’s largest city every six to eight days, Smith told CBC Radio’s Metro Morning. He called on people to “get serious” about physical distancing, masking, handwashing and limiting gatherings.
Epidemiologists look at the effective reproductive number of COVID-19, which indicates how many other people an infected person will pass the virus onto, on average. Public health experts like to see the value significantly below one so cases don’t multiply out of control.
Raywat Deonandan, an epidemiologist and associate professor at the University of Ottawa, said Canada’s current effective reproductive number, or R value, is above one, which by definition is exponential growth.
“It means that we’re in some dangerous territory,” Deonandan said. “I don’t think it’ll get as bad as it was at the peak of this, but it will get bad.”
The Public Health Agency of Canada said in its latest weekly report on Sept. 11 that the effective reproductive number is 1.05.
Since March, physical distancing protocols, mask-wearing procedures and treatments have improved the chances of surviving, he said.
“If we can delay the gratification of the need for intense socializing for several months, our reward will be less suffering, less death and a more open society.”
A front-running team in the race to develop a COVID-19 vaccine has put its late-stage trial on hold after a reported “unexplained illness” in one of the trial volunteers. Here’s what that means for the quick development of a COVID-19 vaccine.
What kind of vaccine trial got put on hold?
The trial was a Phase 3 clinical trial for a vaccine being developed by the University of Oxford and pharmaceutical company AstraZeneca.
It’s the largest type of clinical trial, requiring thousands of volunteers, and is the last of three stages of human testing before a vaccine can be approved for use. Its main goals are to:
Test the efficacy of the vaccine at preventing the disease compared with a placebo
Get a better idea of possible side effects and how often they happen, including rare side effects that might not show up in smaller trials.
The company is running Phase 3 trials involving thousands of people in the United Kingdom and smaller numbers of people in Brazil and South Africa. It is also recruiting 30,000 people in the United States for its largest study.
The vaccine being tested is a non-replicating viral vector vaccine.
AstraZeneca reported Tuesday evening that there was a “potentially unexplained illness” in one of its trials in the U.K.
That triggered a “standard review process,” intended to ensure safety when that happens.
While the trial is suspended, the incident will be investigated by independent reviewers not involved in the trial itself.
What kind of illness was it?
AstraZeneca said Wednesday that the patient had neurological symptoms associated with a spinal inflammatory disorder called transverse myelitis, but a final diagnosis was still pending as more tests are carried out, Reuters reported.
That involves localized inflammation of the spinal cord, which can cause symptoms such as weakness, loss of sensation or even paralysis of the arms and legs. It can be caused by autoimmune diseases, viral, bacterial or fungal infections or parasites, but it has also been reported as potentially a rare side effect of vaccinations for diseases such as influenza or rubella.
However, researchers who have studied it note that it’s difficult to confirm or exclude the link between the disease and vaccination, since it can occur coincidentally due to other causes after vaccination.
WATCH | Infectious disease specialist explains suspension of trial:
Dr. Sumon Chakrabarti, infectious diseases specialist at Trillium Health Partners, said safety is paramount in vaccine clinical trials, and temporary suspensions are not unusual to evaluate any unexplained illness in a participant. 4:31
What is the goal of the review?
It will try to determine whether the illness was related to the vaccine.
Because trials like this are typically double-blinded, the researchers don’t know whether a given volunteer received the vaccine or a placebo. That’s one of the reasons why the review needs to be conducted by an independent committee that is not doing other analyses in the study.
Even if the volunteer received the vaccine, the timing of the illness could still be coincidental and unrelated to the vaccine.
Dr. Sumon Chakrabarti, an infectious disease specialist at Trillium Health Partners in Toronto, told CBC News Network that if the patient does have transverse myelitis, he or she will likely be tested for different types of infections to see if a cause can be determined.
“I’ve seen many of these cases myself, and we often come up with viral causes,” he said.
If that happens, the review may be able to rule out the vaccine as the cause and allow the trial to resume.
AstraZeneca’s halt to a big coronavirus vaccine trial is a cause for concern, says Toronto respirologist Dr. Samir Gupta, who also hailed B.C.’s transparency around growing coronavirus cases. 0:50
How often do pauses like this happen?
On the one hand, they’re not triggered by “mild” side effects, and there haven’t been any publicized for any COVID-19 vaccine trials so far, despite the large number underway. However, AstraZeneca disclosed Wednesday that it had briefly paused a COVID-19 vaccine trial in July after a study volunteer was found to have multiple sclerosis. An independent review panel concluded the illness was not related to the vaccine.
Dr. Samir Gupta, associate professor of medicine at the University of Toronto, said that “it’s not a routine thing to stop a massive trial mid-course like this.”
But on the other hand, it’s not unexpected, given the size of the trial, said Dr. Michael Gardam, an infectious disease specialist at Women’s College Hospital in Toronto.
“I would argue for probably every vaccine that’s ever come to market, there’s been an event like this,” Gardam said.
“When you’re giving vaccine to tens of thousands of people, something’s going to happen to one of them. And chances are it’s happenstance … it’s not linked to the vaccine. But each time, you have to investigate it.”
WATCH | How COVID-19 vaccines are being created quickly and safely:
Some potential COVID-19 vaccines are already in the third stage of clinical trials. It’s taken a lot of effort and money to squeeze a process that can normally take five years into about 10 months and still be done safely. 2:17
Will the pause slow down development of a vaccine?
Gardam said he doesn’t think it will cause a significant delay.
Investigators will try to figure out “a reasonable explanation” for the cause of the illness, Gardam said, which may take some time.
A pause occurred during the Phase 1 trial of a Canadian-made Ebola vaccine in 2014 after several volunteers reported joint pain. An investigation found that the side effect was likely caused by the vaccine, and the study resumed three weeks later with a lower dose.
In this case, Gardam said he thinks it will be hard to draw any conclusion based on one illness and that the University of Oxford researchers will be able to “quite quickly get back up and running again.”
However, they will need to collect more data to see if others show similar illnesses. If that happens, he said, “then that’s a completely different story.”
WATCH | When will a COVID-19 vaccine be ready?:
An infectious disease specialist answers viewer questions about a COVID-19 vaccine including what stage vaccine development is in and when the public could expect one to be ready. 2:58
How worried should we be about this pause?
If it turns out that this is a potential adverse effect of this vaccine, “that would obviously be a substantial showstopper for this vaccine,” said Dr. Andrew Morris, an infectious disease specialist at Sinai Health, the University Health Network and the University of Toronto.
He’s concerned there wouldn’t be access to the vaccine, which is in advanced stages of development. It’s also one that many countries are pinning their hopes on, with substantial investment and three billion doses reserved by governments around the world and by the COVAX Facility, which aims to provide access to more than 70 per cent of the world’s population.
Morris said he’s also concerned that the media coverage will discourage people from enrolling in vaccine studies or increase anti-vaccination hype.
“Any step back is really a setback for all of us,” he said.
But at the same time, researchers such as Gardam say in some ways, the pause should ease people’s concerns, as it shows that the system is working and highlights the importance of Phase 3 clinical trials to ensure the safety of vaccines.
“This in and of itself isn’t a big deal,” he said. “This is what is supposed to happen…. This gives me some comfort.
“The fact that this has been stopped appropriately, it’ll be investigated. We’ll learn about it and then presumably the trial will start up again. That’s exactly what’s supposed to happen.”
Canada has announced that it has signed deals with four U.S. companies to reserve millions of doses of COVID-19 vaccines under development in an effort to make sure Canadians are at “the front of the line” when a vaccine becomes available.
It also said it’s close to a deal with AstraZeneca, based in the United Kingdom.
All of the companies have received funding from the U.S. government’s Operation Warp Speed, which is investing billions of dollars to fast-track the development of promising vaccine candidates.
Canada will receive 20 million to 76 million doses of each vaccine, should any of them successfully make it through clinical trials and be approved by Health Canada.
WATCH | Canada gains access to 2 more potential COVID-19 vaccines:
The federal government has announced deals to buy millions of potential COVID-19 vaccine doses from two American drug companies, on top of its existing deal with two other U.S. firms. The government is aggressively looking for backup plans after its deal with a Chinese company CanSino fell apart recently. 2:06
While they have shown promising results in small-scale, early-stage clinical trials, even those most advanced candidates have only recently begun Phase 3 clinical trials to determine their effectiveness in preventing COVID-19, and there is no guarantee any of them will make it to market. That’s the crucial large-scale human trial that must demonstrate that the vaccine prevents the disease, and it’s the final stage before approval by government.
“What we don’t know, of course, is which vaccines are going to be effective,” Dr. Michael Gardam, medical director of infection prevention and control at Toronto’s Women’s College Hospital, said in an interview with CBC’s As It Happens.
“We don’t know which company ultimately is going to have the best vaccine and the safest vaccine.”
Gardam said the deals represent different types of vaccine from four different manufacturers. The federal government, he said, is “just kind of playing the field … to make sure they have a reasonable chance that one of these will be successful.”
Phase of development: Phase 1/2a trial started in July
How it works: This vaccine, made by a Johnson & Johnson subsidiary, is a new type of vaccine called a non-replicating viral vector. Unlike traditional vaccines made from viruses or parts of viruses, this vaccine uses only a piece of coronavirus DNA. The DNA contains instructions for making a coronavirus protein so that the human body can produce it and learn to recognize it.
The protein targeted by most COVID-19 vaccines, including this one, is called the spike protein or S-protein. It’s found on the outer surface of coronaviruses and is used by the virus to bind to and enter human cells.
In this case, the DNA with instructions for making the spike protein is carried into the body by a common cold virus called an adenovirus. The adenovirus has been genetically modified so it can’t replicate itself in the human body. However, because it’s a virus, it may generate a stronger immune response than the DNA alone and helps get the DNA into human cells, where the spike protein can be produced. One disadvantage of this type of vaccine is that some people may have immunity to some adenoviruses from catching colds, which may make the vaccine less effective.
Where it’s at: The company reported in July that its vaccine protected monkeys against the virus after a single shot. The company started a human Phase 1/2a trial in July in Belgium and the U.S, and it announced this week it is starting a Phase 2 trial in Spain, the Netherlands and Germany. It says it will conduct Phase 3 trials in Argentina, Brazil, Chile, Colombia and Mexico.
WATCH | Federal government’s multiple COVID-19 vaccine deals win praise:
“We just need to have as many sticks in the fire as possible,” says infectious disease specialist Dr. Isaac Bogoch. 3:00
Headquarters: Cambridge, Mass., U.S.
Doses reserved: Up to 56 million
Phase of development: Phase 3 clinical trial started in July
How it works: Moderna’s vaccine candidate is made from messenger RNA, a type of genetic material. Messenger RNA, or mRNA, is used by cells to translate instructions found in DNA to make proteins. In this case, the instructions tell a human cell how to make a stabilized version of the spike protein for SARS-CoV2. That introduces the protein into the body so immune cells can learn to recognize it and produce antibodies against it.
The mRNA is encapsulated in a liquid nanoparticle for injection into the body. The LNP “container” protects it from being degraded by enzymes and helps it enter cells, Moderna says.
The mRNA itself also generates an immune response. While mRNA vaccines have been under development and widely tested for many years, none have ever been approved for widespread human use.
Where it’s at: Moderna launched the first Phase 3 clinical trial in the U.S. in July, and hopes to enrol 30,000 volunteers. The company reported in May that the vaccine produced protective antibodies in a small group of healthy volunteers, and the study showed the vaccine was safe. However, three people in an early-stage trial reportedly had severe or “systemic” adverse reactions, such as high fevers, to a high dose of the vaccine.
WATCH | Fast-tracking a COVID-19 vaccine is not without controversy:
Human challenge trials could make finding a COVID-19 vaccine faster, but the controversial approach involves exposing volunteers to the virus to see if a potential vaccine works. The National’s Andrew Chang finds out more about this process and the people volunteering to be test subjects. 9:01
Headquarters: Gaithersburg, Md., U.S.
Vaccine type: Protein subunit
Doses reserved: 76 million
Phase of development: Phase 1/2 clinical trial started in May
How it works: Novavax’s vaccine is the most traditional of the ones reserved by the federal government. The vaccine is made from nanoparticles of a key protein from the coronavirus that causes COVID-19. When the protein particles are injected into the body with an adjuvant — a compound that enhances the body’s immune response — the body learns to recognize and fight off the virus.
“That is a tried and true way of producing vaccines and of creating immunity,” Dr. Barry Pakes, a professor at the Centre for Vaccine Preventable Diseases at the University of Toronto’s Dalla Lana School of Public Health, told CBC News Network.
It’s similar to vaccines already on the market, such as the hepatitis B vaccine.
Novavax makes the protein by putting the genetic sequence for the protein into a virus that infects insect cells, causing them to make large quantities of protein. The protein has some small genetic modifications compared with the one found on the real virus to help it maintain a rigid shape and make it easier for the body to bind to and recognize.
Protein subunit vaccines don’t elicit as strong an immune response as whole virus vaccines, so they often include an adjuvant. Novavax uses a proprietary adjuvant called Matrix-M, which is based on a type of compound found in many plants called a saponin. The company says it boosts the body’s immune response and generates a bigger immune response with a lower dose.
Where it’s at: Novavax reports in a study preprint (not yet peer-reviewed) that in Phase 1 clinical trials, its protein and adjuvant stimulate high levels of neutralizing antibodies — higher than those in people who have had a natural infection — with few side effects. It’s currently running a combined Phase 1 and 2 trial.
Headquarters: New York, N.Y., U.S./Mainz, Germany
Doses reserved: At least 20 million
Phase of development: Phase 2/3 clinical trial started in July
How it works: Pfizer and BioNTech’s mRNA vaccine is quite similar to Moderna’s. It’s an mRNA sequence for a stabilized spike protein. Like Moderna’s vaccine, it’s delivered in a liquid nanoparticle container.
Where it’s at: Pfizer and BioNTech tested two different mRNA sequences for Phase 1. It reported in a study posted online that has not yet been peer-reviewed that both vaccines generated higher levels of neutralizing antibodies than found in the blood of someone who had had a natural COVID-19 infection. However, the spike protein sequence generated fewer side effects, especially in older adults, so that’s the focus of a combined Phase 2 and 3 trial.