UM Today the Magazine | Fall 2021 | Gone Viral - UM Today

When the first stories about a mysterious respiratory virus began to seep out of China in January 2020, University of Manitoba researcher Keith Fowke was in Kenya for a scientific conference at the University of Nairobi's Institute for Tropical Infectious Diseases. The topic? HIV and other emerging viruses.

But even Fowke, who's spent decades unravelling the mysteries of these conditions—most notably, uncovering a natural immunity to HIV that has transformed how we treat it—was taken aback by the pace and persistence of this new threat.

"The news was concerning, but at first it seemed like a regional issue," says Fowke [BSc(Hons)/88, PhD/95], who is head of UM's department of medical microbiology and infectious diseases. "We didn't correctly anticipate the speed of transmission of the virus or the impact of the disease. It shut down the world economy. COVID-19 caught us by surprise."

Yet, it's possibility was never in doubt. At least not in the ever-alert eyes of infectious disease experts now taking stock of what this pandemic has taught us and what we need to do differently going forward.

"The potential of a virus like this emerging had been anticipated," admits epidemiologist James Blanchard [BSc(Med)/86, MD/86], executive director of the University of Manitoba's Institute for Global Public Health. The worst-case scenario is when you have a virus that is highly transmissible with high levels of severe disease. COVID-19 qualified in half of the equation. "It was very transmissible," says Blanchard, whose research, predominantly in the poorest regions of India, focuses on how the characteristics of individuals, communities and large populations contribute to the distribution of communicable and non-communicable diseases.

COVID-19 bore similarities to the 2002 SARS (severe acute respiratory syndrome) and 2012 MERS (Middle East respiratory syndrome) outbreaks. All three viruses are thought to have jumped to humans from bats and all three are respiratory diseases, but in contrast to the other viruses, COVID-19 moved strikingly fast. While MERS took two and a half years to infect 1,000 people, and SARS took four months, COVID-19 reached that figure in just 48 days. After its initial detection in Wuhan, China, in December 2019 it advanced swiftly across the globe. By the end of March 2020, it had invaded more than 170 countries and sickened more than 750,000 people.

Not only did it spread quickly, SARS-CoV-2 had other characteristics that proved problematic for medical researchers and health workers. Unlike most infectious viruses, it could infect people and cause little effect. "People could get the virus but not have any symptoms. They wouldn't feel sick, so they would continue with their regular activities and infect others," notes Blanchard.

Another complicating factor was a lack of knowledge about its means of transmission. Initially, people were warned about contracting the virus by touching contaminated surfaces and then transferring it to their mucus membranes. But that turned out not to be a major means of transmission. Instead, most cases of infection came through the air.

It has since been established that COVID-19 not only spreads through droplets (short-range globs of spit), but also by aerosols (smaller, dust-like flecks) that can remain suspended in the air and expose individuals at distances beyond two metres from an infected person.

Investigators have also had to deal with the perplexing phenomenon of "superspreaders." Multiple studies have suggested that as few as 10 to 20 per cent of infected people may be responsible for as much as 80 to 90 per cent of transmission, and that many people do not transmit the virus at all. Scientists are still struggling with this enigma, but recent evidence suggests that a person's infectiousness may be connected to how strong a viral load they inhale.

COVID-19 has also developed a terrifying mystique because it behaves in unusual ways. It causes mild symptoms in some but critical illness in others. It is a respiratory virus and yet seems to attack the heart, brain, kidneys and other organs. It has also reinfected some people who had recently recovered.

Another frustrating aspect to the pandemic was how quickly the virus became politicized. "Really to an extent that is unprecedented," says Blanchard. In the U.S., this became an obstacle to slowing the spread as President Donald Trump and his supporters began actively working to undermine public confidence in the very doctors, epidemiologists and public health experts who were working to keep Americans safe.

As the pandemic exploded it also became clear that even the world's most "advanced" government systems were ill prepared to deal with its effects. Masks, personal protective equipment (PPE), diagnostic tools, ventilators, hospital beds and other equipment were in short supply. "It became clear that we were all reliant on the same manufacturers. It exposed the weaknesses in our supply chains," notes Jason Kindrachuk, assistant professor in medical microbiology and infectious diseases and Canada Research Chair in Emerging Viruses at UM.

Considering that the global community had already grappled with two recent coronavirus outbreaks in SARS and MERS, Kindrachuk had hoped society would be better prepared for something like COVID-19, but this wasn't the case. "Once a virus fades from the headlines there is a human tendency to lower one's guard," he says. "It's an out-of-sight, out-of-mind thing. We need to get away from that mindset. We've got to be proactive rather than reactive."

"Once a virus fades from the headlines there is a human tendency to lower one's guard. It's an out-of-sight, out-of-mind thing. We've got to be proactive rather than reactive."

Blanchard concurs. "It's important that we retain a global capacity that looks redundant between pandemics. There has to be a global agenda for this rather than leaving the response up to individual countries."

In Canada, the lack of preparation had a deadly impact. "I was surprised and deeply saddened by the failure of governments and health authorities to provide adequate care and support for elderly persons in long-term care," says Pamela Orr [MSc/94], a UM professor of internal medicine, medical microbiology and community health sciences.

"I was also surprised by the failure to maintain an adequate Canadian stockpile of personal protective equipment," notes Orr. "There was a federal mandate after the 2003 SARS epidemic to maintain an up-to-date pandemic-ready PPE supply, but this was not done. Frontline health workers and patients were initially not provided with adequate PPE, particularly in long-term care facilities, but also in hospitals, and this was a factor in the deaths that occurred."

Although the response to the crisis in some areas was sadly lacking, the global scientific community rallied as scientists dropped whatever intellectual puzzles had previously consumed their time and switched their focus to the pandemic. Kindrachuk, who was at the University of Nairobi with Fowke when the virus began its deadly march, returned home and relocated to Saskatoon where he began working at the Vaccine and Infectious Disease Organization at the University of Saskatchewan. "I was looking at how viruses get into our cells, subvert our immune system and change around the responses in our cells such that they are able to basically create more and more copies of themselves and essentially produce the devastating diseases that we see."

Despite this impressive marshalling of resources and expertise, Fowke points out that, thankfully, "In Canada's primary grant funding agency—the Canadian Institutes of Health Research—money was not diverted from other existing health research programs. Instead, new money was put into the system."

One thing that did change as the result of this medical mobilization was the pace at which information was made available, as scientists began uploading thousands of papers to open-access preprint servers without first going through the normal peer-review process. One study estimated that 23, 634 unique published articles related to COVID-19 were indexed on Web of Science and Scopus between Jan. 1 and June 30, 2020.

"This presents a double-edged sword," explains Orr. "We can rapidly exchange information on a global scale, but the need for critical appraisal has never been more important. The other change has been the speed with which research networks formed and the tremendous cooperation achieved nationally and globally."

For Kindrachuk, the pandemic reminded him of why he entered the field. His interest was sparked by the 1995 medical thriller Outbreak, which dealt with the sudden emergence of an Ebola-like virus in Zaire, Africa. "After seeing the film, I can remember saying, 'I want to do this.'

"I found it fascinating that something as simple as Ebola, whose RNA genome contains just seven genes, could kill 50 per cent of the people it infects," explains Kindrachuk. "It demonstrated how fragile human existence can be. We face these viruses every day. They are all around us. We are at the behest of these organisms."

"We face these viruses every day. They are all around us. We are at the behest of these organisms."

Life would imitate fiction for Kindrachuk when he flew to West Africa in 2014 to help combat an Ebola virus outbreak, the largest since the virus was first discovered in 1976. The epidemic, which began in Guinea before moving to Sierra Leone and Liberia, would kill 11, 232 people.

Kindrachuk feels that COVID's impact will inspire a surge of students to enter the field. (South of the border, where the number of applicants to medical school is up 18 per cent this year, they've dubbed these enrolment increases "The Fauci Effect.")

"Younger generations have been witnessing the devastating effect of the virus globally," says Kindrachuk. "Some will want to devote their lives to the cause of public health."

Blanchard agrees. "The pandemic has raised awareness of the field. Students will see opportunity here."

Fowke, who directs students in the University of Manitoba's International Infectious Disease and Global Health Training Program, believes the pandemic will not only influence how the subject of infectious disease is taught, but will also have an impact on other subjects by introducing such topics as global supply chains into economics classes and the phenomenon of the anti-vaccine movement into social sciences.

For Fowke, the speed and global reach of the virus has highlighted the benefits of even greater international networking. "I think COVID has shown the need for us in Canada to work with other countries as partners. It's important to have connections in other countries." As he notes, Canadian scientists can also learn by studying developing pathogens in far-flung places.

The accumulated knowledge that scientists gain by studying disease pays future dividends, says Fowke, who has spent a good deal of time in Kenya, studying ways of protecting individuals from acquiring HIV. He says that scientific investigations into HIV/AIDS has revolutionized our understanding of the immune system and how diseases subvert it. "Cancer research benefitted HIV research and HIV research has benefitted from cancer research. There are always spinoffs." Fowke is convinced that the research that has been poured into understanding COVID-19 will leave us better equipped for our future wars against harmful viruses.

Even the vaccines now being used against COVID-19 are a product of past research on infectious diseases. Although the vaccines themselves were developed within 12 months, "The platforms that have been used for delivering these vaccines have been worked on for years," says Kindrachuk.

These platforms can theoretically be used to create a vaccine for any infectious disease simply by inserting the proper mRNA sequence for that disease. The Pfizer/BioNTech and Moderna vaccines contain pieces of SARS-CoV-2's genetic material—its mRNA. When volunteers are injected with these particles, their cells use the mRNA to reconstruct a non-infectious fragment of the virus, allowing their immune system to prepare antibodies that neutralize it. "All they had to do is basically figure out what part of the virus they were going to put in the vaccine and then run with it," says Kindrachuk.

"One could regard the speedy development of these vaccines as a crowning achievement of modern science," says Blanchard. However, he doesn't believe that much of the public has enough emotional distance from the pandemic to fully appreciate what has been accomplished. "People are still affected by the losses they've experienced during COVID."

Although Canada was initially hamstrung by not having the ability to produce vaccines and having to depend on delivery from other countries, our nation now ranks first in the world in percentage of people vaccinated. Even so, says Blanchard, "I don't think that we are likely to reach a threshold for 'herd immunity' through vaccination, since the virus will continue to circulate and eventually those who are not immune will likely be infected. So, over time, pretty much everyone will have been either infected or immunized. Where there are pockets of unimmunized populations, we can expect ongoing outbreaks and sporadic cases until most are infected."

Blanchard is well-versed in global health issues having conducted research and public health programs related to HIV/AIDS in India and other south Asian countries.

"Globally, there are still large segments of populations that remain unimmunized in many countries, due to lack of access to vaccines or vaccine delivery systems," says Blanchard. "Tragically, in those countries infection rates will remain high until a very large proportion of the population has been infected."

Exactly how new variants of the SARS-CoV-2 virus might affect future waves is another open question. The longer a virus circulates within a population the more likely it is that variants will develop since with almost every person it infects, the virus changes very subtly—picking up a letter in its genetic code here, another being deleted there, or swapped for something different.

Most of these changes have little effect other than helping scientists to trace how the virus is spreading, but occasionally a mutation occurs that alters how quickly the virus spreads, its level of infectiousness, or the severity of the disease it causes. The extremely contagious Delta variant has been described as being as contagious as chicken pox, with each infected person potentially infecting eight or nine others—a rate four times greater than the original strain of COVID-19.

"The Delta variant has been a game-changer," says Kindrachuk, noting that it's shown the ability to be passed on by vaccinated people. "We really have to get this situation under control, otherwise we run the risk of encountering even more deadly variants."

"The Delta variant has been a game-changer. We really have to get this situation under control, otherwise we run the risk of encountering even more deadly variants."

Whatever happens with COVID-19, the science of infectious disease will never be the same. It has been altered in some fundamental ways.

In the past, respiratory viruses, though extremely common, attracted little funding or interest, largely because they mostly cause mild, cold-like illnesses. But COVID has illustrated how such reasoning is shortsighted as respiratory viruses are the pathogens most likely to cause pandemics, and those outbreaks could potentially be far worse than COVID-19's.

Blanchard believes it is vital to give the World Health Organization (WHO) and other international associations the resources and mandate they need to spot potential threats, collect and share data, and to encourage individual nations to develop specific therapeutics and other health infrastructure that would be needed to stay ahead of disease outbreaks before they become pandemic.

In Pamela Orr's view, the pandemic has exposed serious flaws in our health-care system that need correcting. "We have learned that we have weak public health systems in Canada, and weak governance in terms of making science-based decisions. The pandemic has shown that our primary care and hospital services have been cut to the bone over the past decades, with catastrophic results. The pandemic has also demonstrated yet again something that we have known for a long time but not acted upon—the need for Indigenous peoples to control, and have the resources to deliver, their own health care. In Manitoba the Indigenous-led COVID vaccine program for First Nations was highly successful."

"It's changed our history for better or worse," notes Kindrachuk. "We have come together globally to combat this disease. The pandemic has pushed us to do this, but at the same time it has exposed a lot of problems in our society."

What exactly lies ahead is difficult to predict as the pandemic is not playing out in the same manner from place to place. In some countries it has been controlled, while in others it is still running rampant. At last count, SARS-CoV-2 had infected more than 241 million people and killed nearly 5 million. Sobering statistics, and yet it could have been much worse. Although it spread quickly, COVID-19 hasn't had a high mortality rate. "The mortality rate with SARS was 10 times greater, but that virus didn't last. It faded away," says Blanchard.

COVID-19 is not fading away. Fowke thinks it's possible that we will find ourselves in an arms race with this virus, just like we are with flu. Each year flu vaccines must be updated as the influenza virus mutates and adapts to escape the immunity already present in the population. "COVID-19 may become endemic here and around the world, returning each year like the flu, and perhaps require people to get boosters. Whatever is the case, we won't be protected for life by these current vaccines," he warns. At the same time, with the increased ability to produce and distribute vaccines, "I don't believe the virus will be able to sweep through a population like it has been able to," says Fowke.

"At one point we felt we could eliminate the virus. Now I don't think we will get to that point," admits Kindrachuk, who notes that in many countries in Africa less than 10 per cent of the population has been fully vaccinated. Although we might be able to gain some control of the situation here in Canada, because of the globalized nature of the world the virus will continue to circulate around us.

Kindrachuk says there is an understandable desire among people to believe that the virus is now in the past and we are clear of danger and can resume our normal lives. Appealing as this scenario may be, he suspects it is not entirely accurate. "People may be mentally exhausted and tired of dealing with COVID, but the virus isn't done with us yet."

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