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COVID's Next Big Impact?

August 18, 2022

Living in a “Post-COVID” World. The COV3R Project and Preparing for the Next Possible COVID Wave: Coinfections

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Nearly three years since SARS-COVID-19 (conventionally referred to as ‘COVID’) was declared a global pandemic, much of the world is returning to a sense of normality. While the rate of death from the coronavirus may have decreased, researchers like Dr. Andrew Cameron are helping Canada and the world prepare for another near-term COVID threat: coinfections.

The COVID pandemic has and continues to affect every corner of the globe and forever change how we view and understand the devastating effect of pathogens.

Since its emergence in 2019, COVID has impacted health care systems worldwide. Up to the spring of 2022, at least 6.4 million people have died, and at least 580 million infections have occurred worldwide. These numbers have dominated the conversation about COVID’s effect on society, so much so that how COVID affects people with other respiratory conditions has received little attention.

Understanding how COVID affects people coinfected by a viral or bacterial respiratory pathogen is the main element behind the Genome Prairie and Saskatchewan Health Research Foundation-funded COV3R project. The COV3R project began in the summer of 2020 at the Institute for Microbial Systems and Society (IMSS) in Regina, Saskatchewan, in partnership with the Roy Romanow Provincial Laboratory in Saskatchewan, the Cadham Provincial Laboratory in Manitoba, the British Columbia Centre for Disease Control, and the National Microbiology Laboratory in Winnipeg.

The COV3R project is developing ‘genome capture’ to improve infectious agents’ detection and genotyping. Viruses and bacteria are incredibly small, so they represent ‘needles in a haystack’ in the human respiratory tract. The new technique of genome capture excels at focusing sequencing efforts on pathogens. The capture technique allowed the labs to detect the coronavirus in patients and other respiratory viruses. Moreover, IMSS has demonstrated how genome capture is very powerful for detecting both emerging infectious diseases and unanticipated pathogen variants. The team is expanding the technique to identify diverse viruses, bacteria, and antibiotic resistance genes to better understand the effects and severity of COVID  coinfections.

“We want to sequence other pathogens that may be co-infecting along with COVID, particularly respiratory viruses circulating simultaneously,” said COV3R project lead Dr. Andrew Cameron. “This is important from a clinical perspective because it might be a person infected with COVID and, say, Influenza A. This person will have a much worse disease progression and might need targeted and aggressive treatment because their body is fighting off destructive infections.”

Examining the impact of coinfections is gathering pace and interest beyond the Institute. A recently published report from the U.S. Centers for Disease Control (CDC) has raised the alarm that higher rates of antimicrobial resistance among the general population may occur due to bacterial coinfections with COVID. Recently researchers at the University of Saskatchewan’s Vaccine and Infectious Disease Organization (VIDO) began looking at how patients with coronavirus and tuberculosis are impacted.

Trying to pinpoint coinfections and develop strategies to mitigate their effects on patients poses a massive problem for health authorities. The huge volume of potential viral and bacterial threats means a project like COV3R is faced with a complicated question: where does a project researcher even start to look at the danger?

“There are so many microorganisms in any person’s respiratory tract,” said Cameron, who is also an associate professor at the University of Regina, and IMSS co-founder. “There are hundreds of species of bacteria in your upper respiratory tract at any moment, and there will also be viruses there. We want to survey these microorganisms because there’s also an element of luck. Some microorganisms pose more risk of infection, and some combinations of microorganisms may be a serious health threat.

“Ideally, we would swab a respiratory tract, extract all the genetic material, and sequence it. But right now, sequencing everything is intensive. It’s just not useful from a public health perspective. Putting it all together is really, really hard to do and too big a barrier for time and cost for public health labs.”

There are faster, more focused strategies labs can take. For example, public health relies heavily on the polymerase chain reaction or PCR testing to detect genetic material from specific organisms.

“A shortcoming of PCR is that it is only able to test for a limited number of select pathogens that we’re already aware of,” said Cameron. “Another shortcoming is that when those pathogens mutate, PCR tests can fail.

“So, while PCR is fast, effective, and very sensitive, it has a minimal view of what’s potentially in a person’s respiratory tract.”

An effective solution, says Cameron, is using a “middle ground” strategy in sequencing organisms that could pose significant threats to human health. This approach, hybridization probe capture, forms the foundation of the COV3R project.

“Hybridization probe capture, or ‘genome capture’, is a targeted metagenomic approach. We genotype the known pathogens, we expand our understanding of their diversity, we discover pathogens we didn’t know about before, and we do it more efficiently and cost-effectively.”

Cameron indicated that the COV3R project had already made significant progress in gaining greater insights into the pandemic, mainly tracking how COVID spread through the Saskatchewan and Manitoba population.

However, the COV3R project has run into challenges in understanding the effects of coinfections involving the COVID virus. Ironically, the pandemic had a marked positive effect on the number of coinfections seen among the general public.

“Our behavior changed unlike anything we’ve seen in modern history,” said Cameron. “We avoided community transmission of flu in Canada in 2020 and 2021, and viral coinfections were almost non-existent.

“We stopped the flu because of behavior changes. We worked at home. We did better sanitation. We did social distancing. We stopped the transmission of almost all respiratory viruses we usually monitor, which we know are major causes of infectious disease.”

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The lack of coinfections at the start of the pandemic also had a downside. Many governments, including those in Canada, have recently loosened or eliminated health restrictions to reduce COVID transmission. The growing ‘we’re over COVID’ sentiment concerns Cameron about COVID’s continued spread in the coming autumn and winter months.

“COVID hasn’t disappeared. It’s still out there. It’s still infecting people. It’s still making people sick. The other respiratory viruses haven’t disappeared either. Co-occurrence of these infectious diseases could make the coming months very challenging.”

“I think October is going to be interesting. I know myself and many people who work in the health sector are worried about what could happen this winter.”

Another big challenge in the coming months and years ahead will be higher antimicrobial-resistant bacterial infections. Antibiotic resistance is becoming more widespread, reducing options for treating severe diseases. Unfortunately, little is known about how bacterial infections interact with viruses, yet antibiotics are prescribed as a safeguard when patients are suffering from a severe respiratory infection.

“We’re working on hybridization probe capture to detect antimicrobial resistance genes. For example, diagnostics to tell which antibiotics may be effective for some pathogens like tuberculosis can take months to complete. But suppose you can identify the gene variants that allow the bacterium to be resistant. In that case, it will help in prescribing the best antibiotics.

"This is another example of how genomics has a big advantage over other genetic approaches.”

Even with the premise that the world could be facing future serious COVID challenges, Cameron remains upbeat about how public health systems will use genomic technologies to recognize and respond to future global pandemics.

"The key to better preparing for the next pandemic will be monitoring and anticipating which pathogens can jump from animals into humans. It includes zoonotic pathogens like influenza, coronavirus, and many other types of pathogens, both bacterial and viral.”

Cameron emphasized that genomic sequencing offers researchers and scientists the greatest opportunity for understanding pathogens, both in the present with COVID and the inevitability of future global pandemics.

“In terms of detecting other pandemics and other outbreaks, genomics is certainly the most powerful tool we have to track how pathogens evolve.”