When is a case of COVID still COVID? Critics suggest the gold-standard of testing could be too sensitive


Experts are concerned some people are being ordered to isolate who are no longer infectious or a threat to public health

To understand the latest wrangle over COVID-19 testing, think of trying to identify a single person from a photo of a stadium packed with tens of thousands — a kind of Where’s Waldo hunt.

The gold standard test used to detect the wily virus that causes COVID-19 works much the same way, by searching for miniscule pieces of viral genes from cells and mucus swabbed from someone’s nose. If a trace amount of the virus’ genetic material is detected, it’s amplified, or copied, over and over again, cycle after cycle, each cycle doubling the amount of material and making millions of copies of what you’re looking for — your Waldo.

It’s like zooming in on your computer screen, says Harvard University’s Dr. Michael Mina. “If you have to zoom a lot, then the thing was small to start with,” he recently Tweeted, the “thing” being the starting amount of virus. If you only need to zoom a little, it was a big “thing” to begin with.
Now, some critics are asking, how many rounds, or cycles, are too many? When should you stop hitting “zoom in” and looking for proof of the virus? The likelihood of the person still being infectious can decrease with more cycles, because the test — reverse transcription polymerase chain reaction, or RT-PCR — is so sensitive it can pick up debris from an old infection. It’s detecting genetic material and not live virus, meaning it can be positive after the person has cleared the live organism.
But RT-PCR is a binary yes/no test. No, negative. Yes, positive. Mina and others say it’s not so neat. “We have to stop thinking of people as positive or negative,” he said in an interview published in Science magazine this week, “and ask how positive?”

The concern is that some people are being ordered to isolate who are no longer infectious or a threat to public health, and that provinces are encouraging mass testing using a hyper-sensitive test that’s churning out daily cases numbers, the implication being that a case always equals an active infection equals a person capable of spreading to others.

“We do know that PCR picks up dead organism that is not infectious,” says Dr. Vanessa Allen, chief of medical microbiology at Public Health Ontario. “I think a lot of the discussion is, do we in fact need a test that’s so sensitive, and what is the meaning of those tests at the very end threshold? Are they actually the people we need to isolate?”

In Canada, most labs set the limit of cycles to detect the virus’ genetic material, or RNA, to between 35 and 40 cycles, though some Ontario labs have “positivity” cut-offs as high as 45 cycles, according to a study first flagged by Westphalian Times. Mina, a physician and epidemiologist, thinks the cut-off should be closer to 30. (The number of cycles to detect RNA is known as the cycle threshold, or CT value.)

Read full article here.

Sharon Kirkey – National Post – October 2, 2020.

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