Healthcare workers do testing at a drive-thru COVID-19 assessment centre at the Etobicoke General Hospital in Toronto on April 21, 2020. The spectre of headline-grabbing false-positive test results should not rattle the public's confidence in efforts to track COVID-19 in Canada, observers say. Despite a spate of recent examples including the false alarm in Nunavut, several experts insist the phenomenon remains rare given the scope of tests administered in the country, which reached the benchmark of 1-million tests last week. THE CANADIAN PRESS/Nathan Denette

TORONTO - The spectre of headline-grabbing false-positive test results should not rattle the public's confidence in efforts to track COVID-19 in Canada, observers say.

Despite a spate of recent examples including the false alarm in Nunavut, several experts insist the phenomenon remains rare given the scope of tests administered in the country, which reached the benchmark of 1-million tests last week.

Nevertheless, the scare in Pond Inlet, a tiny community on the northeastern coast of Baffin Island, raised many questions about how and why a COVID-19 test incorrectly came back positive, and whether it's possible to eliminate such errors, even if they are unusual.

It didn't help that the mistake came amid a false positive scandal at an Ottawa laboratory where dozens of positive COVID-19 test results were rejected because of suspected errors.

Then there was the much-publicized South Korean study that initially suggested COVID-19 reinfection was possible, until researchers said the findings were likely marred by false positive test results.

Here's a look at what the experts have to say.

HOW ACCURATE IS COVID-19 TESTING?

Medical experts struggle with test accuracy all the time, Nunavut's chief public health officer said when the error came to light.

Dr. Michael Patterson apologized for the inconvenience caused by the error, but noted Nunavut was far from the only region to have weathered problems: "False positives are an issue that every jurisdiction has dealt with."

All lab tests have limitations, agrees Christine Nielsen, chief executive officer of the Canadian Society for Medical Laboratory Science.

"It's a terrible thing to say but there is no test that is perfect," says Nielsen. "Even if we have 99.99 (per cent) accuracy, which is a fantastic number, it means that some of them need to have further investigation."

The accuracy of a medical test is measured in two ways: How often it correctly finds people with the disease, and how often it correctly finds people without the disease.

Timothy Sly, a professor emeritus at Ryerson University's School of Occupational and Public Health, says this is the difference between a test's sensitivity and its specificity.

"The sensitivity is to say: How many of the true positives have we really got? And therefore, the others are false. And the specificity is: How many of the true negatives were we able to find? And of course the others are false," he says.

Many factors can affect these outcomes, including the quality of the sample itself, the type of tools used to obtain and assess the sample, and at what stage of infection the sample was obtained. Patterson said that variability makes it hard to define a hard-and-fast accuracy rate.

"False negatives can occur, certainly up to 30 per cent of the time if we swab people who are asymptomatic and swab them too soon after they've been exposed to COVID-19," said Patterson.

"False positives depend a lot on the machine itself, but also how much COVID-19 is in a town or community that you're assessing or sampling. And so it's really hard to nail down a rate that applies to every machine that we use."

WHERE AND HOW DO THINGS GO WRONG?

In the case of COVID-19, the virus that causes the disease — SARS-CoV-2 — is detected through a test known as a reverse-transcription polymerase chain reaction test, or RT-PCR.

It works by detecting viral RNA from a sample provided by the patient, usually by way of a throat swab or a nasopharyngeal swab.

This can be uncomfortable for the person being tested, says Sly, noting the nasopharyngeal swab is a long flexible device that must reach deep into the nose to collect enough material.

"If you just poke it once it's not going to have a chance to pick up as much virus as if you touch the membrane and then twist a couple of times," he says.

"This little small variation on who's doing the task can change it."

PCR, meanwhile, is "a very finicky test," says Nielsen.

"Let's say there's 100 steps in a process. If you make a mistake in step one, your mistake will be amplified," says Nielsen. "This is one of those areas where standard operating procedures and how the lab functions — doing it the same way every single time — is really important."

WHAT'S THE IMPACT OF A FALSE POSITIVE RESULT?

While both have bad outcomes, Nielsen suggests a false positive is better than a false negative in terms of public health risk because it forces the person to take extra — rather than inadequate — precautions.

"You at least go into isolation," she says, suggesting the alternative leads to community spread.

Nevertheless, the personal cost can be high, especially if forced quarantine prevents someone from working or caring for dependants, Nielsen acknowledges.

Add to that the general emotional and psychological toll wrought by isolation and a COVID-19 diagnosis, and the impact is considerable.

Plus, there are still infection risks to incorrectly assuming you have COVID-19, says University of Toronto professor Ashleigh Tuite of the Dalla Lana school of public health.

"The challenge with the false positive is that if you think that you're infected, do you isolate yourself and then assume that you're immune and then behave in a way that isn't protective against reinfection?" she says.

False positives also trigger further public health costs since staff must identify the infected person's close contacts and make sure they are not infected. In the case of Nunavut, more than a dozen people were tested for COVID-19 but none of those tests came back positive.

False positives can also inflate the true scope of infection in a particular community — numbers which shape public policy around containment measures such as school closures, the shutdown of non-essential services and public gatherings.

WHAT CHECKS ARE IN PLACE?

Even if a test has proven to be extremely reliable in development, things can go awry once it's deployed in the real world.

That's what appeared to happen with the handheld Spartan Cube, an Ottawa-made diagnostic device that was recently recalled because its swab design made it prone to false negatives. Health Canada downgraded its authorization to research use only.

"That's not unusual where you have a very, very well-performing test in very idealized situations and then when you do it in real life, it never works as well," says Tuite.

The Spartan recall is an example of Canada's regulatory system working well, adds Nielsen.

She says laboratories also have lots of quality control measures to limit the possibility of machine and device errors, while the power of regular observation is not to be underestimated.

"You'll have somebody that's in ICU and all of their labs come back normal but you hear that they're in multi-organ failure, that suggests to you that there's something wrong."

In detailing what went wrong in Nunavut, Patterson described diagnostic tests as just "one piece" of "an entire system of measures to intervene on COVID-19 infection."

He credited the work of public health nurses to trace contacts in quelling fears the disease had spread.

"When in doubt, we aim to err on the side of caution," he said.

This report by The Canadian Press was first published May 10, 2020.

News from © The Canadian Press, 2020