American patients who have gone through hell and high water to get a coronavirus test may be alarmed to learn about false negatives – what happens when a patient who actually has the virus gets a negative result on a laboratory test.
The rate of accuracy for nasal swab tests, the mechanism overwhelmingly used to diagnose for coronavirus, is still in question. One widely-cited study of 205 Chinese patients found that samples collected from nasal swabs detected coronavirus in only 63 percent of patients who had the disease.
Dr. Bruce Patterson, a Stanford pathologist, told a Berkeley TV station last week that he expects false negatives from nasal swab tests to arise in 10 to 15 percent of samples – a number he says is in line with other viral diseases like the flu.
Other medical professionals agree with Patterson that the level of inaccuracy in tests doctors are seeing is not unusual in a viral disease like Covid-19. Dr. Jon McCullers, dean of clinical affairs at the University of Tennessee Health Science Center, told a Memphis TV station this week that a lab test with 100 percent accuracy for a disease like coronavirus yields only “maybe 70 or 75% accuracy in the real world.”
The FDA’s fact sheet on the COVID-19 test for New York healthcare providers states that “a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions.” The FDA goes on to advise providers to assess negative results “in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19,” especially considering any recent exposures the patient may have had and any telltale symptoms, and advises repeat testing in some cases.
Test negative? You should still Assume you might be infected, Yale doc says
Even if you test negative, you should assume that — especially if you have the symptoms — you might be infected, Harlan Krumholz, M.D., a Yale professor of medicine, wrote in The New York Times. “Across the world, people with signs and symptoms of Covid-19 are testing negative and wondering what it means. They are not showing up in the statistics, and they are left in limbo about what to do next,” he wrote.
“The problem may be with the test. Current coronavirus tests may have a particularly high rate of missing infections. The good news is that the tests appear to be highly specific: If your test comes back positive, it is almost certain you have the infection. … The best the Centers for Disease Control and Prevention can say is that if you test negative, ‘you probably were not infected at the time your specimen was collected.’ The key word there is ‘probably.’”
Regardless of the accuracy issue, it seems clear that New York has a high level of positive testing.
Half of NY tests came back positive in one day
“Whoa: Half of the coronavirus tests processed last night in New York came back positive. (About 9,000 positives out of 18,000 tests)” Brian Rosenthal of The New York Times tweeted on March 31. “That is … a high percentage. The state is now at 75,795 cases”
A CityMD source wrote on a private Facebook page: ‘We have sent over 16,000 covid 19 tests in the last weeks and with selective testing (meaning not testing everyone due to lack of supplies) our positive rate is 57%.”
Of course, testing itself is not proof that someone is not transmitting the virus. People without symptoms are considered to be a surprisingly high number of infected people, perhaps as many as 25 percent, according to The New York Times.
Why is this so?
What, exactly, is to blame for false negatives? And what’s the implication for our current crisis?
First, there’s the question of how sick a patient is when they take the test. At the time of administering the test, doctors say, a patient’s viral load could be too low for the disease to be accurately detected. Retesting the same sick patient just a few days later may yield a more accurate result.
“If I go get a test with someone who just started to get sick and so they’re infected but they don’t have much virus in them maybe it’s negative,” Dr. McCullers said. “But maybe if I test them three days later, it’s going to be positive because there’s a lot more virus in them at that point.”
Another simple explanation for false negatives: the test can be hard to administer, making it sometimes difficult to obtain a good sample from the patient.
One ED nurse speculated on a popular Reddit forum that “poor swabbing technique” might be to blame for bad samples. The swab has to go very far back in the nasal cavity, and rushed or stressed doctors and nurses may not be able to efficiently collect the sample.
“Let’s say you had a swab that wasn’t obtained very well. … The person has the virus. But the nurse or physician just barely puts it into the nose because the person is backing up — we would not have a good specimen, so it could create a false negative in the test,” Gary Procop, director of molecular microbiology, virology, mycology and parasitology at the Cleveland Clinic, told the Washington Post.
Craig Blakeley, the dean of the University of Louisville’s School of Public Health and Information Sciences, told the Columbus Dispatch that conditions at outdoor drive-through testing sites like wind and cold could yield worse samples than if the subject was sitting still in a perfect laboratory setting.
“If they came in and they have every classic symptom and they have been in contact with someone else who had COVID-19, and they test negative, I wouldn’t believe that as being the definite negative test,” McKinney said. “I would retest that person in 24 to 48 hours to see what’s going on. If you have multiple negative tests, that increases the likelihood that it’s for real.”
The implications are severe
Again, the tests are crazy hard to get — see these blog posts of ours for 1) how to get a test and 2) how much that test will cost. The assumption has been that if you actually get a test, that’s an achievement — and maybe you’re home free.
But not so quick.
The implications for false negatives can be severe in the United States, especially given how poorly medical and social systems are handling the crisis and the scarcity of available tests. Many workers, especially hourly workers or independent contractors with companies like Uber and Lyft, have reported that they need to show a positive test in order to get sick pay from their workplaces – a requirement that goes against advice from the CDC. A negative test may also encourage a contagious person to return to work or socialize with friends and family and transmit the disease further.
The accuracy of tests may also be putting medical professionals at risk, as hospitals scramble to handle growing loads of patients and dwindling supplies of masks, gowns and other personal protective equipment – and as doctors and nurses get sick from inadequate protection.
What a negative test means
One anecdote we heard: Patient got tested, results did not arrive, but he got worse and went to the hospital. Upon hospitalization, doctors judged him to be COVID positive, tested him and placed him in a COVID ward. Two days later, his hospital test came back negative, and he was removed from the COVID ward. Then his pre-hospital test came back (11 days later) with a positive result.
One New York doctor recounted what a false negative test meant for them and their colleagues on a Reddit thread, after admitting a 73-year-old man with “multiple comorbidities” who tested negative:
[The patient] is taken off the vent within 24 hours and discharged to the floors. Because he’s COVID negative you see. .
Yesterday, my team and I thought “This guy has a normal white count, elevated LFTs and recurrent fevers. Forget the last test, order a repeat COVID.”
I do this several hours before speaking with the attending physician. During table rounds, he pointedly asked me if I was aware of the protocols the Command Center had put in place for repeat testing. I say no, as these protocols change every day. (Side note: N95s are now rated for indefinite use, not just 4 days. Hope we didn’t toss all those other ones away for no reason!) “Cancel the test, let’s get Infectious Disease on board and ask them their input.”
I put in for the ID consult, I… “forget” to cancel the COVID repeat or inform the Command Center. Busy day as you saw from yesterday. Comes back positive. We know what this bastard virus looks like.
But we spent 2-3 days in his room without our N95s on.
We would have spent more in there had we not tested.
A doctor reported on Reddit that he wanted to return an employee to full duty by testing her and finding her negative. Her results? Negative, positive, negative, positive, negative, positive, negative. The protocol for returning her to work was two serial negative tests — but he used 7 tests and never got that result.
Buzzfeed reported on April 3 that a 42-year-old educator in Queens died of complications from coronavirus after initially testing negative in the hospital.