New research shows more than 20 % of coronavirus cases are being missed by testing — known as "false negatives" — with one expert saying the results could require a rethink of Australia's COVID-19 strategies.The "test-and-trace" method is a permanent fixture in the global coronavirus arsenal, but these new findings indicate diagnosis may not be as clear cut — or accurate — as first thought.
COVID-19 testing relies on a type of test called rt-PCR, or just PCR, which looks for viral genes in a sample collected with a swab.
If the sample contains any of the virus, it will almost always pick it up.
Because of this, many have assumed that PCR gives very few "false negative" results — that if you have the virus, the PCR will not come back negative.
<< I've been warning about this here and elsewhere for a while now , and this has been discussed several times on MEDCRAM >>
But that thinking has come under serious scrutiny recently.
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The best data so far is a study from Johns Hopkins University in the US, which pooled the results from seven studies and a combined 1,300 test results.
It found that, in fact, people confirmed to have coronavirus almost never got a positive result in the first three days of their infection.
The best time to test someone was between six and eight days after infection.
But even then, the tests still missed about one-in-five confirmed cases.
ref
https://www.acpjournals.org/doi/full/10.7326/M20-1495
sked about this issue on Tuesday, Victoria's Chief Health Officer Brett Sutton said people who had already been tested but were not getting better should get a repeat test.
"If you've got ongoing symptoms and you've had a negative test, then consider retesting," he said.
He said sometimes false-negative tests were a technical issue with the swab or the lab."But sometimes it's where you're at in your illness and it may well be picked up on a different occasion," Professor Sutton said
If those figures represent contagious people being released into the community — a matter still being debated — that is a serious problem, according to Tony Blakely, an epidemiologist and public health expert from the University of Melbourne.
"If we take these false negatives seriously, which I do, it has a number of serious implications," Professor Blakely said.
1) it meant the number of real cases was higher than was being recorded and which public health officials were relying on.
2) he said it would make Australia's suppression strategy — where tries to keep the virus at manageable levels in the community instead of eliminating it — much harder to implement.
"It could be — I emphasise 'could' — a reason why the 'test and contact trace' strategy failed in Victoria," he said.
Suppression relies on finding true positive cases and isolating them. If we miss some of those cases, Professor Blakely said ensuring suppressed levels stay low enough could be difficult.
He also said Australia might need to change the way it defined a positive case: that symptoms and contact with other cases might need to be used to define a positive case, even in the face of a negative PCR result.
If false negatives were a real problem, Professor Blakely said "presumptive isolation" would be necessary — a concept where people suspected of having the virus are required to isolate, regardless of their test result.
That was the advice given by NSW Chief Health Officer Kerry Chant this week to people who visited the Crossroads Hotel between 3 and 10 July.
"Even if you get a negative test, that does not mean you are out of the woods and hence we are asking that you isolate yourself for 14 days since you were last at the Crossroads Hotel," Dr Chant said.
"A negative test does not mean you can breach self-isolation." << or you are in the clear and get on with your normal life >>
The rationale behind Dr Chant's directive is referred to as "negative predictive value (NPV
<< see previous posts >>. False negatives are more likely among a group of people who are very likely to have the virus, such as people who were on the Ruby Princess or family members of a confirmed case.
But in the general population — where very few people have the virus — false negatives have been believed to be not very common.
Are false negatives a 'problem'?
Professor Sutton said people who tested negative were unlikely to spread the virus.
"There's no capturing people who have very low viral numbers and maybe they're less infectious so it's less of an issue," he said.
Bill Rawlinson, a virologist from the University of New South Wales, agreed.His lab conducts thousands of COVID-19 tests each day and looks for possible false negatives by comparing PCR tests with blood antibody tests.
"Because I'm a laboratory person as well as a clinical person I ask how does it look in the community [if] this was a major problem then we should have seen it in the last six months," he said.
"At a population level, there should have been lots of outbreaks caused by this. [But] we're not seeing lots of outbreaks."
He said that based on the evidence, a change of policy direction was not warranted.
But Professor Rawlinson said some false negatives could be caused in other ways.One possibility was that the virus had not infected the precise part of the nasal passage swabbed.
Alternatively, there could be a reservoir of the virus elsewhere in the body. Again, not just where the person was swabbed.
He said work he did on pandemic influenza in 2009 showed that could happen. But he was sceptical it was happening a lot with COVID-19.
"They were very sick with pneumonia," he said of the flu patients.
"Nasopharyngeal swabs were negative but when we could get a lung sample or [an immunological test] and they were clearly positive," he said.
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