Ontario back to square one, experts say
Province urged to boost investment to get ahead of new variants of virus
With increasing reports of new, more dangerous COVID-19 variants in Ontario, experts say the province urgently needs more genomic sequencing, faster results, and policies that stifle the virus’s opportunities to evolve — a situation reminiscent of the earliest days of the pandemic, when the disease outstripped our ability to track and control it.
The province has ramped up surveillance for three red-flag “variants of concern,” which were first detected in the U.K., South Africa and Brazil. Unlike the many viral strains with mostly benign genetic alterations, these three variants carry a host of mutations that scientists believe makes them significantly more contagious or potentially able to evade some immune defences in previously infected and vaccinated people.
This past week, the Simcoe Muskoka public health unit announced that six samples from a vicious outbreak at the Roberta Place nursing home in Barrie had preliminarily screened positive for one of those variants. On Saturday, the health unit said that full genome sequencing confirmed the presence of the U.K. variant in all six. Twenty-nine residents have died after 124 of 127 tested positive for COVID-19 in less than two weeks, along with 84 staff and two visitors.
Public Health Ontario has asked every lab in the provincial COVID-19 testing network to forward all positive samples from Wednesday to be analyzed for the variants of concern — a single-day snapshot of about 2,630 cases. Initial results will be available in two to three weeks, according to Dr. Vanessa Allen, PHO’s chief of microbiology and laboratory science.
Outside of that “point-prevalence” study, the agency is conducting full sequencing on about 350 samples a week, and is poised to triple its capacity to carry out preliminary screening tests. Hospital and university labs are boosting those volumes, including a next-generation, ultra-high-throughput sequencing platform that will soon begin screening hundreds of samples from Toronto daily.
But experts say further investment is needed — financial and logistical — to make sure officials can catch and act on new information in time.
“This feels like FebruaryMarch 2020 in some ways,” says Dr. Samira Mubareka, a microbiologist at Sunnybrook Health Sciences Centre, who has been involved in sequencing viral genomes from the beginning of the pandemic.
Canada is sequencing about five per cent of positive COVID-19 samples to hunt for variants, Mubareka says, about half of what the U.K. is achieving.
“At five per cent, you would have to have quite a few variants floating around to pick one up. And then you realize, well, it’s just the tip of the iceberg. By then you’re already in a bit of trouble.”
Developing fast, cheap screening tests for variants — ones that give a preliminary yes-orno answer — is underway, experts say. By this week, PHO will be able to screen up to 1,500 weekly samples, according to a spokesperson. (With the six Roberta Place samples, Ontario has caught 21 confirmed cases of the U.K. variant and none of either the South African or Brazilian ones out of 4,000 tests since September.)
But fully sequencing viral genomes — getting every word on every page of the genetic instruction manual, not just a yesor-no — is critical to understanding exactly what strains are circulating, including notyet-identified or even homegrown variants, a realistic threat at this stage of the pandemic.
Turnaround times for full genome sequences need to improve from the current two to three weeks, Mubareka says, pointing to the Roberta Place outbreak: Public health needs actionable information, not a weeks-old snapshot.
Expanding the province’s genomic surveillance capacity involves more than just buying sequencing instruments, Mubareka says. Similar to the bottlenecks that have stymied conventional COVID-19 testing, it also requires ensuring that information flows quickly through the system — including supporting public health to carry out the same functions that have been vital since the very first case.
“There’s no point in generating this data if there aren’t those key track-and-trace teams on the other side to say, ‘OK, we’ve got this, we’re on it,’ and can actually intervene in an impactful way.”
At Sinai Health’s LunenfeldTanenbaum Research Institute, scientists are working to adapt a next-generation, ultrahigh-throughput sequencing platform to screen hundreds of positive samples for variants daily.
The platform is designed to sequence small genome sections very quickly and in huge volumes. Pre-pandemic, the scientists were using it to study cancer. This year, they worked to convert it into a system that could process thousands of conventional COVID-19 tests, research that is still advancing.
In December, researchers in the U.K. announced that a viral strain carrying a host of mutations was spreading rapidly, and appeared to be roughly 50 per cent more transmissible. The Sinai team pivoted again, adapting the platform to process hundreds of lab samples that already tested positive by rapidly sequencing “fingerprint regions” of the viral genome to look for key mutations.
“Three weeks later, (the information is) not as helpful,” says Jeff Wrana, a senior investigator at LTRI who is leading the project. “We need to get it within days.”
The team recently carried out a proof-of-concept experiment, analyzing 900 positive COVID test samples from Sinai’s lab. They hope to start screening every positive sample from Sinai soon — around 400 a day.
Nearly all screening results from the pilot run were unremarkable, long-circulating strains of the virus, Wrana says.
According to genetic sequences uploaded to GISAID, an open-access database that researchers use to share, track and compare SARS-CoV-2 lineages, the team also found a small number of a viral variant from Brazil. This lineage, known as P.2, is not the same as the Brazilian variant of concern, which has not been detected in Ontario.
“We’re keeping an eye on it, because it could pick up more mutations and become a variant of concern. But at this point it’s just something we’re tracking and keeping an eye on. We’re not particularly concerned about it,” says Andrew McArthur, a professor and bioinformatics specialist at McMaster University’s Michael G. DeGroote Institute for Infectious Disease Research.
McArthur and Mubareka belong to the Toronto Invasive Bacterial Diseases Network, which in December and January also identified a small number of P.2 strains in Ontario, according to GISAID.
P.2 does not carry the spike protein mutation known as N501Y that is shared by all three red-flag variants, associated with significantly increased transmissibility. Aside from N501Y, the three variants of concern boast a large number of mutations in key regions, and scientists are working furiously to understand their combined effects.
The strain Wrana and others identified in Toronto, however, does have a mutation known as E484K, which both the South African and Brazilian variants of concern share. Scientists are worried about variants carrying E484K, because laboratory experiments, case reports of reinfection and epidemiological evidence from South Africa and Brazil suggest the mutation helps evade immune response in people who have already been infected or vaccinated.
The real-world impacts of this are unclear, and even less clear in strains like P.2 that carry one “watchlist” mutation but not the full suite of worrying changes. Our immune systems have an armada of cellular defences, and weakening one part of the system doesn’t neutralize all of it. The Pfizer and Moderna vaccines in particular are so effective that losing some efficacy may not matter, and they can also be retooled quickly if necessary.
PHO’s Allen says that until the significance of key mutations are better known, the agency and local health units are carrying out additional case investigation for samples with strains carrying mutations like E484K as well as for the official variants of concern.
But that uncertainty is also why we need to remain vigilant — especially right now, scientists say.
“Never underestimate a virus or the cleverness of evolution. These variants are popping up all over,” Wrana says. “They should be aggressively monitored and controlled, because if they do have significant immune evasion properties, it would be devastating.”
Mubareka and McArthur both noted that public health policies and personal behaviour also have a significant effect on the evolution of new variants: Every time the virus is transmitted, it has a chance to evolve.
“The simplest way to reduce the risk of new variants is to drive the numbers down. It’s as simple as that,” McArthur says.