HomeMy WebLinkAbout20200902_S Schumacher_COVIDFrom:Stephen Schumacher
To:Board of Health
Cc:Tom Locke; news@ptleader.com
Subject:NYTimes: too-sensitive PCR tests leading to 90% false positives
Date:Wednesday, September 2, 2020 1:56:00 PM
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Dear Jefferson County Board of Health,
Per the August 29 New York Times report atbottom, I'm concerned about the criteria used todetermine confirmed cases of COVID-19 in Jefferson County.
Do all these cases exhibit symptoms, or are"cases" being equated to positive testresults? If the latter, what percentage of cases exhibit symptoms?
Are positive test results being recorded usingPCR tests, and if so, what is the Cycle Threshold(C.T.) value used for these tests?
Note that "In three sets of testing data thatinclude cycle thresholds, compiled by officialsin Massachusetts, New York and Nevada, up to 90percent of people testing positive carried barelyany virus, a review by The Times found. ... InMassachusetts, from 85 to 90 percent of peoplewho tested positive in July with a cyclethreshold of 40 would have been deemed negativeif the threshold were 30 cycles, Dr. Mina said.'I would say that none of those people should becontact-traced, not one,' he said."
Also bear in mind Dr. Deborah Birx's statisticaladvisory that when prevalence is low (as inJefferson County), "If you have 1% of thepopulation infected and you have a test that isonly 99% specific, then if you find a positive,then 50% of the time it will be a real positiveand 50% of time it won't be." That's because the1% false positives found from the 99% uninfectedwould be about equal to the 1% truepositives. So best-case scenario, it may be that33%-50% of Jefferson County's 3% positive tests are false positives.
But if Jefferson County does its PCR testingusing excessive Cycle Thresholds, perhaps an evenhigher percentage of our 70 confirmed cases are in fact false positives.
Two final general questions:
(1) Given that COVID-19 has been out in the wildthroughout the general population for months,
what is the point of continued contact tracing?
(2) Given that deaths and hospitalizations have
been stable or declining nationwide sincemid-April regardless of cases, isn't that thesame thing as attaining herd immunity?
Yours truly,Stephen Schumacher2023 E. Sims Way #200Port Townsend, WA 98368
---https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html
Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.
The usual diagnostic tests may simply be toosensitive and too slow to contain the spread of the virus.Tests authorized by the F.D.A. provide only ayes-no answer to infection, and will identify aspositive patients with low amounts of virus in their bodies.
By Apoorva MandavilliAug. 29, 2020
Some of the nation’s leading public healthexperts are raising a new concern in the endlessdebate over coronavirus testing in the UnitedStates: The standard tests are diagnosing hugenumbers of people who may be carrying relativelyinsignificant amounts of the virus.
Most of these people are not likely to becontagious, and identifying them may contributeto bottlenecks that prevent those who arecontagious from being found in time. Butresearchers say the solution is not to test less,or to skip testing people without symptoms, asrecently suggested by the Centers for Disease Control and Prevention.
Instead, new data underscore the need for morewidespread use of rapid tests, even if they are less sensitive.
“The decision not to test asymptomatic people isjust really backward,” said Dr. Michael Mina, anepidemiologist at the Harvard T.H. Chan School ofPublic Health, referring to the C.D.C. recommendation.
“In fact, we should be ramping up testing of alldifferent people,” he said, “but we have to do itthrough whole different mechanisms.”
In what may be a step in this direction, theTrump administration announced on Thursday thatit would purchase 150 million rapid tests.
The most widely used diagnostic test for the new
coronavirus, called a PCR test, provides a simple
yes-no answer to the question of whether a patient is infected.
But similar PCR tests for other viruses do offersome sense of how contagious an infected patientmay be: The results may include a rough estimateof the amount of virus in the patient’s body.
“We’ve been using one type of data foreverything, and that is just plus or minus that’s all,” Dr. Mina said. “We’re using that forclinical diagnostics, for public health, for policy decision-making.”
But yes-no isn’t good enough, he added. It’s theamount of virus that should dictate the infectedpatient’s next steps. “It’s really irresponsible,I think, to forgo the recognition that this is aquantitative issue,” Dr. Mina said.
The PCR test amplifies genetic matter from thevirus in cycles; the fewer cycles required, thegreater the amount of virus, or viral load, inthe sample. The greater the viral load, the morelikely the patient is to be contagious.
This number of amplification cycles needed tofind the virus, called the cycle threshold, isnever included in the results sent to doctors andcoronavirus patients, although it could tell themhow infectious the patients are.
In three sets of testing data that include cyclethresholds, compiled by officials inMassachusetts, New York and Nevada, up to 90percent of people testing positive carried barelyany virus, a review by The Times found.
On Thursday, the United States recorded 45,604new coronavirus cases, according to a databasemaintained by The Times. If the rates ofcontagiousness in Massachusetts and New York wereto apply nationwide, then perhaps only 4,500 ofthose people may actually need to isolate and submit to contact tracing.
One solution would be to adjust the cyclethreshold used now to decide that a patient isinfected. Most tests set the limit at 40, a fewat 37. This means that you are positive for thecoronavirus if the test process required up to 40cycles, or 37, to detect the virus.
Tests with thresholds so high may detect not justlive virus but also genetic fragments, leftoversfrom infection that pose no particular risk akin to finding a hair in a room long after a person has left, Dr. Mina said.
Any test with a cycle threshold above 35 is too
sensitive, agreed Juliet Morrison, a virologist
at the University of California, Riverside. “I’mshocked that people would think that 40 could represent a positive,” she said.
A more reasonable cutoff would be 30 to 35, sheadded. Dr. Mina said he would set the figure at30, or even less. Those changes would mean theamount of genetic material in a patient’s samplewould have to be 100-fold to 1,000-fold that ofthe current standard for the test to return apositive result at least, one worth acting on.
“It’s just kind of mind-blowing to me that peopleare not recording the C.T. values from all thesetests, that they’re just returning a positive ora negative,” one virologist said.Credit...Erin Schaff/The New York Times
The Food and Drug Administration said in anemailed statement that it does not specify thecycle threshold ranges used to determine who ispositive, and that “commercial manufacturers and laboratories set their own.”
The Centers for Disease Control and Preventionsaid it is examining the use of cycle thresholdmeasures “for policy decisions.” The agency saidit would need to collaborate with the F.D.A. andwith device manufacturers to ensure the measures“can be used properly and with assurance that we know what they mean.”
The C.D.C.’s own calculations suggest that it isextremely difficult to detect any live virus in asample above a threshold of 33 cycles. Officialsat some state labs said the C.D.C. had not askedthem to note threshold values or to share themwith contact-tracing organizations.
For example, North Carolina’s state lab uses theThermo Fisher coronavirus test, whichautomatically classifies results based on acutoff of 37 cycles. A spokeswoman for the labsaid testers did not have access to the precise numbers.
This amounts to an enormous missed opportunity tolearn more about the disease, some experts said.
“It’s just kind of mind-blowing to me that peopleare not recording the C.T. values from all thesetests that they’re just returning a positive ora negative,” said Angela Rasmussen, a virologistat Columbia University in New York.
“It would be useful information to know ifsomebody’s positive, whether they have a highviral load or a low viral load,” she added.
Officials at the Wadsworth Center, New York’s
state lab, have access to C.T. values from tests
they have processed, and analyzed their numbers
at The Times’s request. In July, the labidentified 794 positive tests, based on a threshold of 40 cycles.
With a cutoff of 35, about half of those testswould no longer qualify as positive. About 70percent would no longer be judged positive if the cycles were limited to 30.
In Massachusetts, from 85 to 90 percent of peoplewho tested positive in July with a cyclethreshold of 40 would have been deemed negativeif the threshold were 30 cycles, Dr. Mina said.“I would say that none of those people should becontact-traced, not one,” he said.
Other experts informed of these numbers were stunned.
“I’m really shocked that it could be that high the proportion of people with high C.T. valueresults,” said Dr. Ashish Jha, director of theHarvard Global Health Institute. “Boy, does itreally change the way we need to be thinking about testing.”
Dr. Jha said he had thought of the PCR test as aproblem because it cannot scale to the volume,frequency or speed of tests needed. “But what Iam realizing is that a really substantial part ofthe problem is that we’re not even testing thepeople who we need to be testing,” he said.
The number of people with positive results whoaren’t infectious is particularly concerning,said Scott Becker, executive director of theAssociation of Public Health Laboratories. “Thatworries me a lot, just because it’s so high,” hesaid, adding that the organization intended tomeet with Dr. Mina to discuss the issue.
The F.D.A. noted that people may have a low viralload when they are newly infected. A test withless sensitivity would miss these infections.
But that problem is easily solved, Dr. Mina said:“Test them again, six hours later or 15 hourslater or whatever,” he said. A rapid test wouldfind these patients quickly, even if it were lesssensitive, because their viral loads would quickly rise.
PCR tests still have a role, he and other expertssaid. For example, their sensitivity is an assetwhen identifying newly infected people to enroll in clinical trials of drugs.
But with 20 percent or more of people testingpositive for the virus in some parts of thecountry, Dr. Mina and other researchers arequestioning the use of PCR tests as a frontline diagnostic tool.
People infected with the virus are most
infectious from a day or two before symptomsappear till about five days after. But at thecurrent testing rates, “you’re not going to bedoing it frequently enough to have any chance ofreally capturing somebody in that window,” Dr. Mina added.
Highly sensitive PCR tests seemed like the bestoption for tracking the coronavirus at the startof the pandemic. But for the outbreaks ragingnow, he said, what’s needed are coronavirus teststhat are fast, cheap and abundant enough tofrequently test everyone who needs it even if the tests are less sensitive.
“It might not catch every last one of thetransmitting people, but it sure will catch themost transmissible people, including thesuperspreaders,” Dr. Mina said. “That alone woulddrive epidemics practically to zero.”