If the dangerous changes to COVID were widespread in Ontario, would we know? Why scientists care

With growing reports of new, more dangerous COVID-19 mutations in Ontario, experts say the province urgently needs more genomic sequences, faster results, and policies that prevent the chances of the virus developing – a situation that reminds us of the earliest days of pandemic, when the disease was beyond our ability to detect and control.

The province has investigated three “various concerns”, first found in the UK, South Africa and Brazil. Unlike the many viral strains with incapacitated genetic changes, these three mutations contain a number of mutations that scientists believe make them much more contagious or that may avoid some immune defenses. the people who were previously infected and vaccinated.

Last week, Simcoe Muskoka’s public health unit announced that six samples from a brutal uprising at Roberta Place nursing home in Barrie had tested positive for one of these variables. On Saturday, the health unit said full genome classification confirmed the UK variant in all six. Twenty-nine residents have died after 124 of 127 positive tests for COVID-19 in less than two weeks, along with 84 workers and two visitors.

Ontario Public Health has asked all laboratories in the region’s COVID-19 testing network to submit all positive samples from Wednesday to be analyzed for the anxiety variables – a one-day picture of about 2,630 cases. Initial results will be available in two to three weeks, according to Dr. Vanessa Allen, PHO head of microbiology and laboratory science.

Outside of that “point frequency” study, the group is fully sorting out about 350 samples a week, and is ready to carry out its three-stage capability of screening tests. Hospital and university labs are bolstering those numbers, including an ultra-high-throughput next-generation series platform that will begin screening hundreds of samples from Toronto every day.

But experts say more investment is needed – both financial and procurement – to ensure officials can capture and implement new information in time.

“This feels like February-March 2020 in some ways,” says Dr. Samira Mubareka, a microbiologist at the Sunnybrook Center for Health Sciences, who has been involved in the sequencing of viral genomes from the onset of the pandemic.

Canada sends about five percent of advanced COVID-19 specimens to hunt for conversions, Mubareka says, about half of what the UK achieves.

“At five per cent, it took a good number of changes to sail around to build one. And then you realize, well, it’s just the tip of the iceberg. By then you are already in trouble. “

The development of rapid, inexpensive screening tests for variables – ones that provide an initial yes or no response – is underway, experts say. By this week, PHO will be able to screen up to 1,500 weekly samples, according to a spokesperson. (With all six samples of Roberta Place, Ontario has confirmed 21 cases of various UK and none of the South African or Brazilian out of 4,000 trials since September.

But following viral genomes as a whole – getting every word on every page of the genetic guide, not just yes or no – is crucial to understanding what just circulating strains, including as yet unrecognized changes or even domestic, a reasonable threat at this stage of the pandemic.

Turnaround times for full genome sequences must evolve from the current two or three weeks, Mubareka says, marking the departure at Roberta Place: public health needs workable information, not e picture for a week.

Expanding the region’s genomic analysis capability involves more than just purchasing prescription instruments, Mubareka says. Like the bottles that have stopped the standard COVID-19 test, it also needs to ensure that information flows quickly through the system – including public health support to the -perform one task that has been critical since the beginning.

“There is no point in generating this data unless the major search and discovery teams on the other side say, ‘Okay, we have this, we have it,’ and we can inter- make an effective impact. ”

At the Lunenfeld-Tanenbaum Research Institute at Sinai Health, scientists are working to transform an ultra-high-throughput regenerative series platform to record hundreds of advanced samples for daily changes.

The platform is designed to sort small genome segments very quickly and in large numbers. Pre-pandemic, the scientists used it to study cancer. This year, they worked to turn it into a system that could process thousands of standard COVID-19 tests, research that is still ongoing.

In December, researchers in the UK reported that viral snoring carrying a number of mutations spread rapidly, and appeared to be around 50 per cent more susceptible. The Sinai team shook again, changing the platform to test hundreds of laboratory samples that were already positive by quickly adding “fingerprint areas” of the viral genome to look for key highlights.

“Three weeks later, (the information is not so helpful),” said Jeff Wrana, LTRI’s senior investigator who is leading the project. “We have to get it within days.”

The team recently conducted a diagnostic test, analyzing 900 COVID positive test samples from the Sinai laboratory. They hope to start screening all advanced samples from Sinai soon – around 400 per day.

Almost all screening results from the pilot run were unmarked, long stretches of the virus, Wrana says.

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According to genetic sequences uploaded to GISAID, an open access database that researchers use to share, locate and compare SARS-CoV-2 lines, the team also found a small number of viral differentiation from Brazil. This line, called P.2, is not the same as the Brazilian anxiety difference, which was not found in Ontario.

“We’re keeping an eye on it, because it could be causing more changes and cause for concern. But at this point it’s just something we’re monitoring and tracking. We’re not particularly concerned about it, ”said Andrew McArthur, professor and bioinformatics expert at McMaster University’s Michael G. DeGroote Institute for Infectious Disease Research.

McArthur and Mubareka belong to the Toronto Invasive Bacterial Diseases Network, which also identified in December and January a small number of P.2 strains in Ontario, according to GISAID.

P.2 does not carry a spike protein mutation called N501Y that is shared by the three red flag changes, associated with a much larger transmission. In addition to the N501Y, the three anxiety modifications boast a large number of shots in key regions, and scientists are working hard to understand their combined effects.

The Wrana strain and others identified in Toronto, however, have a mutation called E484K, which shares both South African and Brazilian anxiety changes. Scientists are concerned about variants carrying E484K, as laboratory tests, case reports of reinterpretation and epidemiological evidence from South Africa and Brazil suggest that the mutation helps by avoiding an immune response in people who have already been infected or vaccinated.

The real-world impact of this is not clear, and even clearer in series like P.2 that have one “watch list” movement but not the full set of worrying changes. Our immune systems have an armada of cellular defense, and the weakening of one part of the system does not neutralize everything. The Pfizer and Moderna vaccines in particular are so effective that it may not be necessary to lose some effectiveness, and they can also be rewritten quickly if necessary.

Allen at PHO says that in order to better know the meaning of key findings, the agency and local health units are conducting an additional case study for samples with rays carrying mutations such as E484K in addition to the official variables. of concern.

But that uncertainty is also why we need to be vigilant – especially right now, scientists say.

“Don’t underestimate the virus or the wisdom of evolution. These variations are happening across the country, ”says Wrana. “They should be closely monitored and controlled, because if they have large defensive defenses, it would be devastating.”

Mubareka and McArthur both noted that public health and personal behavior policies also have a major impact on the evolution of new changes: every time the virus is removed, it has a chance to come onwards.

“This is one of the most dangerous parts of the pandemic. Generating new changes is about time and patient numbers, and we’ve had a lot of both, ”says McArthur.

“The simplest way to reduce the risk of new changes is to move the numbers down. It’s as simple as that. ”

Kate Allen
Kate Allen is a Toronto-based reporter covering science and technology for the Star. Follow her on Twitter: @katecallen

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