July 20, 2020
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, something else, or perhaps several somethings?
“Coinfection is a problem because any time your body has to fight multiple infectious diseases, that can compromise the ability of your immune system to protect you,” says Andrew Cameron.
Cameron, a microbial geneticist at the University of Regina, together with molecular epidemiologist David Alexander of Manitoba’s Cadham Provincial Laboratory and virologist Amanda Lang at Saskatchewan’s Roy Romanow Provincial Laboratory, lead Genome Prairie’s COVID-19 Rapid Regional Response (COV3R) project. The COV3R team also includes members of the Institute for Microbial Systems and Society at the University of Regina (Cameron is co-director) and the British Columbia Centre for Disease Control.
The COV3R initiative aims to tackle the problem of detecting co-infections, and in the process provide powerful new tools for public health. Coinfections can allow several pathogens to “gang up” and become deadly. A well-known example is HIV, which isn’t lethal by itself. Rather, it weakens the immune system, leaving the body vulnerable to other potentially fatal infections. Little is known about coinfections with COVID-19.
Cameron explains that current tests for COVID-19 and other diseases are based on polymerase chain reaction (PCR). These look for genetic markers that are representative pieces of DNA or RNA from a virus or bacterium. The technology is excellent at finding disease-causing pathogens – but only if scientists have found the best markers. “You can’t detect what you don’t test for,” says Cameron.
An added problem is what the pandemic is doing to testing capacity. Laboratories (and the experts to run them) are flooded with COVID-19 testing, forcing them to reduce testing for other respiratory pathogens. “We’re missing big pieces of the picture for other diseases in Canada at the moment because COVID-19 is the priority.”
Cameron and Alexander, with a team of virologists and microbial geneticists, are working to develop testing based on genome capture. The technique enriches the DNA and RNA from all possible viral pathogens, even those scientists don’t yet know about. Cameron explains this will directly complement genetic sequencing of 150,000 coronaviruses as part of Genome Canada’s Canadian COVID-19 Genomics Network (CanCOGeN) initiative.
“With our relatively small number of coronavirus sequences, we are absolutely dependent on CanCOGeN data to put the Manitoba and Saskatchewan genomes that we sequence in a broader provincial and national context,” notes Cameron.
Genome capture would add a powerful tool to the capabilities of provincial public health testing labs. “Through the design of this technology, we’re 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 help guide doctors to prescribe the appropriate treatment for their patients,” says Cameron.
“Misdiagnosis is a problem with infectious disease because of the limited number of signs and symptoms. Even in the modern day and with all our fancy techniques, we still in many parts of the world attribute disease sometimes to the wrong culprit.”
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 explains that provincial testing labs are slowly coming off their “all COVID, all the time” situation by adding multiplex testing that can look at usual priorities such as influenza A, B, and respiratory syncytial virus (RSV, which chiefly affects infants but is also a serious problem for the elderly). There are unknowns.
Cameron relates how, in fall 2019, the US military used the 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. It was when colleagues in Central Africa began to send samples of unknown coronaviruses for sequencing that pushed Cameron’s focus from bacteria to viruses.
Then came a novel coronavirus and the pandemic. “That’s the game changing part that excites me the most, that we learn so much more biological diversity. We find pathogens we didn’t even know were circulating.”
One of the implications of genome capture testing is it offers the ability to track viruses throughout a population by their unique genetic makeup. This could allow 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 populations.
“Whole genome sequencing is revolutionizing epidemiology. No other technology comes close,” concludes Cameron.
Genome Prairie’s COVID-19 Rapid Regional Response (COV3R) project includes a partnered funding contribution from Saskatchewan Health Research Foundation (www.shrf.ca).