COV3R: U of R’s genome capture project detects COVID-19, the flu, or anything else that ails you

By Genome Prairie and University of Regina Advancement and Communications

You’ve got a cough. You’re short of breath. You’re weak, feverish, beset with chills, and to top it off, you’ve got a splitting headache. Is it COVID-19? The flu? Or is it a combination of several different illnesses hitting you at the same time?


“Co-infection is a problem because any time your body has to fight multiple infectious diseases, it can compromise the ability of your immune system to protect you,” says Dr. Andrew Cameron, a microbial geneticist at the University of Regina.


Cameron, together with molecular epidemiologist David Alexander of Manitoba’s Cadham Provincial Laboratory and virologist Amanda Lang at Saskatchewan’s Roy Romanow Provincial Laboratory, received funding to lead Genome Prairie’s COVID-19 Rapid Regional Response (COV3R) project. The COV3R team also includes research associates, Dr. Keith MacKenzie, Dr. Kara Loose, and master’s student Danae Suchan, members of the Institute for Microbial Systems and Society at the University of Regina where Cameron is co-director, the British Columbia Centre for Disease Control, and University alum and molecular epidemiologist Ryan McDonald at the Roy Romanow Provincial Laboratory.


Genome Prairie provided $240,000 in funding for the project, and the Saskatchewan Health Research Foundation (SHRF) contributed $50,000, while the Centre for Disease Control in B.C., the Roy Romanow Provincial Laboratory in Saskatchewan, and the Cadham Provincial Laboratory in Manitoba have provided in-kind support.


Dr. Gerald Brown, Genome Prairie’s interim President and CEO, says Genome Prairie is thrilled to be supporting the research team’s work.


“The COV3R project represents our organization’s ability to bring together the best researchers in our Prairie provinces to respond rapidly and effectively to an emerging issue,” says Brown.


The COV3R initiative aims to tackle the problem of detecting co-infections in humans, and in the process provide powerful new tools for public health.


Co-infections can allow several pathogens to “gang up” on a person’s immune system and become deadly. A well-known example of this is HIV, which isn’t lethal by itself, but rather, weakens the immune system, leaving the body vulnerable to other potentially fatal infections. Little is known about co-infections with COVID-19.


“Current tests for COVID-19 and other infectious diseases are often based on polymerase chain reaction (PCR), a common technique used in labs to detect the DNA or RNA from viruses or bacteria that cause disease,” explains Cameron. “The technology is fast and efficient for detecting pathogens we already know about. However, PCR is unable to detect new or unknown pathogens that aren’t yet well-characterized. A further complication is that known pathogens can escape PCR detection by evolving new genetic sequence. The most important information for fighting infectious disease is identifying the causative agent–-but, you can’t detect what you don’t test for.”


To help fill that knowledge gap, the COV3R team is working to develop testing based on genome capture. This technique enriches DNA and RNA from pathogens, giving researchers the ability to test for all viral groups, even those scientists don’t yet know about.


“Misdiagnosis is a problem with infectious diseases because of the limited number of signs and symptoms that people experience – such as a fever, a sore throat, and a headache. So even in the modern day with all our advanced techniques, we still sometimes attribute disease to the wrong culprit.”


Cameron says that genome capture can help in diagnosing infectious diseases by adding a powerful tool to the capabilities of provincial public health testing labs.


“Our work with genome capture will directly complement genetic sequencing of 150,000 coronaviruses as part of Genome Canada’s Canadian COVID-19 Genomics Network (CanCOGeN) initiative,” explains Cameron. “We will sequence coronavirus genomes along with co-infecting viruses, then can examine the Manitoba and Saskatchewan coronavirus infections in broader provincial, national, and international contexts through integration with CanCOGeN.”


Through the design of this genome capturing technology, the researchers will be able to detect and then sequence part or even the whole genome “of pretty much every virus type that’s known to infect the human lung, which can then help guide doctors to prescribe the appropriate treatment for their patients,” says Cameron.


In the case of SARS-CoV-2 (the virus that causes COVID-19), the COV3R team is also developing a unique tool that efficiently captures genetic material and compares it against all coronaviruses known to infect animals. It will be a valuable asset both in the current pandemic and for early detection of coronavirus pathogens in the future.


Cameron describes how, in fall 2019, the US military used this genome capture technique in West Africa in their efforts to help combat Ebola and other hemorrhagic fevers. What they found was a whole host of infections of completely different viral groups all causing similar symptoms. At the same time, colleagues in Central Africa began to send samples of unknown coronaviruses to the Institute for Microbial Systems and Society at the University of Regina for sequencing, prompting Cameron to study viruses as well as bacteria.


Then came a novel coronavirus and the pandemic, which immediately re-focused his attention.


“This is the game changing part that excites me the most–-that we learn so much more about biological diversity,” says Cameron. “There are an estimated 1.5 million viruses that can infect mammals and can potentially infect humans, but we only know the genetic sequence of a few hundred specific types. Now we have the ability to find pathogens we didn’t even know were circulating in people.”


Another key feature of genome capture testing is that it offers the ability to track viruses by their unique genetic makeup. This allows public health officials to compare, for example, coronavirus causing COVID-19 cases in different parts of a province or region with virus strains from elsewhere to find out where the disease is coming from and how it’s moving through communities.


“Whole genome sequencing is revolutionizing epidemiology. This technology has the potential to discover so much. With it, we might find something circulating here that we didn’t know we had. No other technology comes close,” says Cameron.


The technology will also address the added problem of what the pandemic is doing to testing capacity.


Laboratories (and the experts who run them) are flooded with COVID-19 testing, forcing them to reduce testing for other respiratory pathogens. “We’re missing pieces of the puzzle for other diseases in Canada at the moment because COVID-19 is the priority,” says Cameron.


He explains that provincial testing labs are slowly coming off of their “all COVID, all the time” situation by adding multiplex testing that can test for their usual priorities, such as influenza A and B, and respiratory syncytial virus.


Dr. Kathleen McNutt, Vice–President (Research) at the University of Regina, says without this work the people of Saskatchewan, Manitoba, and BC will likely be hit even harder by the coronavirus, especially come the fall when cold and flu season re-emerges.


“Thanks to the support from Genome Prairie and SHRF, the work that Dr. Cameron and the COV3R team are doing is poised to make a dramatic difference in detecting COVID-19, and a multitude of other viruses and bacteria that are yet unknown,” says McNutt. “It is not an overstatement to say this research is a matter of life and death.”


SHRF CEO Patrick Odnokon says SHRF has been a strong supporter of Cameron and his team since 2013, including earlier work evaluating whole genome sequencing to enhance our understanding of disease transmission.


“Dr. Cameron is a perfect example of the expertise that exists in Saskatchewan to seek solutions to health challenges faced by our province and across the globe. The impact of this work will not only benefit public health during the current pandemic, but it will demonstrate what is possible when we nurture and support home-grown talent and collaboration to prepare for potential health crises in the future.”


Related Article COV3R – Genome Capture Detects COVID-19 Virus (and Everything Else)

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