Family medicine

For Dalhousie’s Dr. Alyson Kelvin and her father Dr. David Kelvin, a passion for understanding, treating and preventing pandemics has put them at the forefront of international research on COVID-19 vaccines and bio-markers.

On the night of December 30, 2019, Alyson Kelvin was at home in Halifax, on the other side of the world from Wuhan, China. She was just about to put down her book, shut out the light and bring a fulfilling day of Christmas vacation to an end.

Until she checked her email one last time and found an alert from the ProMED infectious disease listserv detailing a mysterious new disease outbreak. “2019-12-30, 23:59:000. Re: Undiagnosed pneumonia—Chine (HU): Request for Information. Some medical institutions in Wuhan have successively appeared patients with pneumonia of unknown cause…” Suddenly, sleep moved far down her priority list.

“I’m not an alarmist, so I didn’t jump on it and wave my arms like, ‘The next deadly pandemic is coming,’” she says, thinking back to her first read of that email alert. “But I knew we had to be working on this. Pneumonia, something hitting our respiratory track, is very concerning—that’s how we breathe, and also how viruses are easily spread,” she says. 

There was also the high number of patients; the report indicated at least 27 were known at the time. “That suggested either everyone who was being infected had to be hospitalized—so the virus was very severe—or that what we were seeing, more like a flu, is that the hospitalizations really indicate the severe cases, the tip of the iceberg.”

In the days ahead, Dr. Kelvin, an assistant professor in Dalhousie’s Faculty of Medicine, would be communicating regularly with colleagues at vido, a world-leading vaccine centre located in Saskatoon, Saskatchewan. Less than two months later, she would upend her entire life to travel there and work hands-on with the virus that would eventually be known as COVID-19—the coronavirus that would spark the largest global pandemic in a century.  

But that night, Dr. Kelvin’s first outreach wasn’t to vido. It was to a Dal colleague, one who has been there for her as a collaborator and confidant her entire career—and then some.

She called her father, David.

A pandemic spans borders. Those researchers tasked with addressing its many challenges must do the same—working across jurisdictions, across disciplines and, in the case of the doctors Kelvin, across generations. 

David, a professor in the Department of Microbiology and Immunology, has been a key figure in emerging infectious disease research for decades. His work is international in scope, carrying out studies with home bases in China, Italy and Canada.

“My interest in diseases evolved out of hiv,” he says. “hiv is what I’d call a slow pandemic: it wasn’t something that spread in a matter of weeks, it took years and it really affected everybody in my generation who was going through our early 20s at that point… My work evolved out of trying to understand the molecular mechanisms of infectious diseases and, in regard to pandemics and epidemics, why some people got serious illness and other people did not.”

You can trace David’s career through several major infectious disease outbreaks over the past 30 years, but the 2003 SARS epidemic stands out as a major flashpoint. He was a researcher in Toronto when SARS  began moving through the health-care system there. So, too, was Alyson: having just completed her undergraduate degree at Western University, she was doing a summer internship at a local hospital. Her work involved screening health-care workers for symptoms while also working with SARS patient samples.

“I was seeing SARS on two levels: both how to socially contain an emerging virus or a virus now spreading through a community, and also working on the science of what’s actually happening in molecular medicine,” she says. “I think that was really influential to me in how I viewed public health and research goals.”

It was never a given that Alyson would follow her father’s path into disease research; for a while she wanted to be a surgeon, or an astrophysicist. But both father and daughter recall vividly that Alyson had an innate childhood curiosity with everything David was doing in the lab, which she would often visit as a toddler. “She was fascinated by infectious disease as far back as I can remember,” says David.

“My work evolved out of trying to understand why some people got serious illness and others did not.”

Dr. David Kelvin

“I recall being really interested in all the discussion around HIV at the time as well,” says Alyson. “That’s what gave me this vision of working in an isolation room with highly pathogenic viruses.”

Following a PhD that was more focused on molecular science, Alyson returned to diseases, studying an outbreak in Italy of a mosquito-borne virus called chikungunya that had recently migrated to continental Europe from Africa. Shortly after—and not for the last time in her career—a pandemic intervened: the 2009 H1N1 swine flu pandemic, which immediately became her new research focus. The experience was both professional and personal for Alyson.

“I was four months pregnant, researching viruses with the threat of a new pandemic that had a second wave anticipated to happen right when my daughter was due,” she recalls. “I was very much a vulnerable population. So trying to understand age and developmental processes and how that was a risk factor [for diseases] became not only a research priority, but a piece of my life.”

Alyson and David’s respective careers continued separately, each in their own fields, but always linked through the family connection—sharing notes, ideas and insights whenever they caught up with one another. 

Which brings us back to that phone call last December.

“I think I told her to go back to bed,” David Kelvin recalls with a hearty laugh.

It was the time of day, more so than the news itself, that inspired David’s initial reaction to Alyson’s phone call. He knew the unknown outbreak in China was something to watch but admits he wasn’t sure, at first glance, just how wary he should be.

“It was really over the next two or three days that the cases dramatically increased and [Alyson and I] had several discussions about it,” he says. “It started to have all the hallmarks of human-to-human transmission.”

In the weeks to come, David would begin an international research collaboration trying to identify biomarkers for patients infected with the new coronavirus. A biomarker is any sort of biological “tell” that helps a patient or health-care professional determine how and when to apply a particular therapeutic—for example, how glucose levels help a diabetes patient decide when to apply insulin. With COVID-19, the idea is to find biomarkers that can help sort out which patients are at risk of more serious infections and, therefore, more likely to require intensive medical care.

“Many people who go on to have severe illness from COVID-19 don’t have severe symptoms in the early stages—those don’t develop until about the end of the first week of illness. What we’re really trying to do is develop methods to test individuals at the earliest stages and identify which of them would go on to have a severe illness, and where those specific biomarkers would tell us how best to treat them.” 

David began by assembling a research team from 15 different countries—even more are involved now—some of which ended up being among the regions most affected by the outbreak’s first wave, including Spain and Italy. Collaborating with local health-care systems, his team gained access to thousands of blood samples and medical files. The aim is to identify two or three simple tests that will help front-line health-care professionals assess which patients are most likely to become serious cases—not only saving lives, but also conserving essential resources for those who need them most.

“If an area sees a large outbreak of cases—like in Spain, or Italy, or this summer in Texas—we see that ICU beds are in very limited supply just because of the sheer number of people infected with COVID-19. This will help identify people who are likely to develop a severe illness and give those people the highest priority for ICU beds.”

An explosion of cases that leads to icu beds filled with sick and dying patients is among the worst possible outcomes in a pandemic like COVID-19. The best possible outcome is that a widely available vaccine, or group of vaccines, successfully limits the spread of the virus, allowing people to resume more of their usual way of life.

Alyson Kelvin is one of many researchers around the world working to develop and test COVID-19 vaccines. Her research model uses ferrets to understand how potential vaccines work in different types of patients: in older individuals, in pregnant women, in children and toddlers.

“We all have a vested interest in developing a vaccine that is going to be effective and safe.”

Dr. Alyson Kelvin

“Vaccination is different in all these age groups,” she explains. “And we know with COVID-19 that there’s a higher mortality rate for people in older age groups. If we can understand why we have those high rates of death, it will be incredibly important to developing specific therapeutics for that age group.”

Through January and February, Alyson began collaborating with colleagues at vido in Saskatoon who were working to acquire physical samples of the virus to start conducting studies. Despite running one of the highest-security labs at Dalhousie, Alyson knew vido’s clearance level was higher. Leaving her colleagues and family behind in Halifax wouldn’t be easy—“I knew then that, a month from now, our lives were not going to be the same, and I was going to be out here [in Saskatchewan]”—but it quickly became her best opportunity to acquire and work quickly with the virus. The first COVID-19 samples in Canada, from the country’s first patient in Toronto, arrived just as the paperwork came together.

Being hands-on with the COVID-19 virus in the lab has significant advantages, and not just for Alyson directly. It’s allowed her to support other researchers at Dalhousie, like vaccine work by Dr. Roy Duncan, Dr. Marianne Stanford and Dr. Chris Richardson or anti-virals being developed by Dr. Craig McCormick. And she’s been able to help coordinate the varied and diverse international vaccine research currently underway as part of the advisory group on pre-clinical animal model development and vaccine evaluation for the World Health Organization.

“We all have a vested interest in developing a vaccine that is going to be effective, safe and able to provide protection to a great number of people—but this isn’t going to happen with just one vaccine,” says Alyson. “We need multiple options for several reasons: we have different vulnerable groups, different groups that are going to be more receptive to a vaccine over another, and just capacity for making these vaccines will be so different all around the world.”

As the summer heat turns to autumn chill, the fear among epidemiologists is that the coronavirus won’t necessarily cool down—that a second wave of cases may begin moving through regions that have seen lower infection rates through the summer. At the same time, experience in other countries where cases continue to rise suggest that, one way or another, COVID-19 will continue to be part of our lives in a significant way in the months and, possibly, years to come—even with vaccines. 

Alyson is optimistic about the likelihood of a widely available vaccine in 2021, but even a vaccine with strong efficacy rates will leave some populations vulnerable to the disease. Additional supporting measures, like antivirals and other therapeutics, will be necessary, as will continued public health guidelines to protect one another from infection while further effort on vaccine and therapeutic refinement continues.

“We all have to work together,” says David, speaking with concern about countries that have taken a more casual or cavalier attitude towards the virus. “Whether it’s for the next pandemic or just in the coming months, we have to do a better job of convincing the entire public to get on the same page when it comes to following basic public health measures. Because if we’re not, we’ll have a global community where the virus continues to move around.”

That’s one of the many subjects that Alyson and David talk about in their regular check-in conversations. Alyson is used to being the one having to track David down somewhere in the world for these, but this summer the roles were reversed: David was at home in Halifax and Alyson was away in Saskatoon. (She’ll be there for the next year; her family joined her in August.)

For David, part of what’s been particularly inspiring about Alyson’s work through the pandemic’s first months is not just her prominent role with respect to global COVID-19 vaccine development but her public engagement as well.

“She’s not only driving important research forward but she’s out there in the media trying to bring these complex problems to the public and communicate things clearly,” he says. “We need people out there taking that leadership role.”

“We do very different work,” says Alyson, “but at the end of the day it’s great to have somebody like that to bounce ideas off of.”