If test says you have coronavirus, believe it. If it’s negative, don’t be so sure
Dr. Anthony Fauci, the national infectious disease expert, says we simply can’t know how many Americans have COVID-19 until more of us are tested.
But the scarcity of test kits may not be the only reason for the undercount.
The testing itself, doctors and researchers are finding, may have troubling flaws. By some estimates, 30 percent of people with the virus aren’t flagged by the testing method most commonly used today.
So even when the time comes that we do have more test kits, there’s a fear that these “false negative” test results will provide a corresponding false level of security, making it more likely that the disease will continue to spread.
“I’m terrified by this,” Kevin Latinis, a doctor at Cass Regional Medical Center in Harrisonville, Missouri, said during one of his recent “chat & chew” lunchtime talks that he has with co-workers about the coronavirus and then posts on YouTube.
Latinis has patients that he suspected were infected with the disease, so when test results turned up negative, he became suspicious and worried. The patients are health care workers who wonder when they can safely return to their jobs.
“We have too few tests, it’s too cumbersome and one thing that is not being widely discussed is what happens if you have false negatives?” Latinis told his audience that afternoon as he stood before them wearing a Royals ball cap, face mask with a Kansas City Chiefs logo and a T-shirt celebrating America’s hero of the moment: FAUCI THE REAL MVP.
“When you’re dealing with this crisis, I can’t emphasize enough how concerning any degree of false negatives is.”
Latinis, who lives in Leawood, has a medical degree from the University of Iowa as well as a doctorate in immunology, internal medicine and rheumatology. He does not claim to be an expert on coronavirus testing, but he is not the only one voicing his concerns.
Writing in The New York Times this month, Yale University medical professor Harlan Krumholz said patients showing symptoms of COVID-19 and their doctors should not believe a negative test result is anything close to an all-clear, given the number of false negatives.
“Current coronavirus tests may have a particularly high rate of missing infections,” Krumholz said in his op ed. As such, if you test negative and have COVID-19 symptoms, he said, assume you have the disease and take appropriate steps.
“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.”
And the bad?
“False-negative test results — tests that indicate you are not infected, when you are — seem to be uncomfortably common. Increasingly, and disturbingly, I hear a growing number of anecdotal stories from my fellow doctors of patients testing negative for coronavirus and then testing positive — or people who are almost certainly infected who are testing negative.”
Also weighing into the discussion was Dr. David Bluemke, editor of the influential medical journal “Radiology,” which has received more than 500 research publications on the disease.
One study has gotten a lot of attention. Researchers at the largest hospital in Wuhan, China, monitored more than 1,000 COVID-19 cases during a single month this year.
They found that nearly 30 percent who initially tested negative for COVID-19 were later found, through other diagnostic methods, to have contracted the disease.
The initial nasal swab testing method that failed to detect infection in Wuhan is the one most commonly used to screen for the disease in the United States.
Based in Madison, Wisconsin, Bluemke has put out a series of podcasts the past couple of months summarizing the studies, many of which focus on the accuracy of the coronavirus tests and how other diagnostic tools, such as CT scans, can be used to screen for COVID-19.
Bluemke has a personal interest in the topic. He came down with some sort of viral or bacterial illness about the time the pandemic spread here.
He tested negative, but wondered whether he could trust the result after reading how the Centers for Disease Control and Prevention botched its first attempt to develop a reliable test and then did what Bluemke felt was too little to verify the second one worked better.
“COVID testing has a nearly 100 percent detection rate in the lab,” he said in his latest podcast. “But in real life, in people, it’s only 70 percent. Why?”
Why false negatives?
The Kansas Department of Health and Environment said that as of 8 a.m. Friday, 1,166 confirmed cases of COVID-19 have been reported in the state since the start of the outbreak, and 10,248 other tests conducted by state and private labs have shown negative results.
In Missouri, the Department of Health and Senior Services recorded 3,799 confirmed cases out of 40,480 tests performed by public and private laboratories as of 2 p.m. Friday.
Neither state agency, nor the CDC, have any idea what percentage of those test results are potentially false negatives because the numbers simply aren’t available. You’d have to do multiple tests on every negative to find out.
Even then, there are simply too many variables at work to compare one lab’s false negative rate to another. A lot comes down to how each patient’s specimen was collected and handled prior to analysis.
“Every paper about performance of any given test, there is significant concern given to the variability in the sampling protocol relative to test results,” KDHE said.
The test for COVID-19 is commonly referred to as an RT-PCR, short for reverse transcription polymerase chain reaction. The same type of test is used to diagnose HIV, measles and mumps.
Conducted under ideal circumstances, the COVID-19 test has a 3 percent rate of producing a false negative, according to the CDC.
But circumstances are almost never ideal outside a lab. Experts say the potential for error is tied to how and when specimens are collected for analysis, not to mention the potential for contamination down the line.
The process begins with the uncomfortable and sometimes painful method of collecting a specimen for that analysis. Be it in an emergency room, doctor’s office or a drive-thru screening, a health-care worker inserts into your nostril a long, bristle-ended probe — think of it as a very long and coarse cue tip — called a nasopharyngeal swab. Then the worker pushes it up your nasal cavity about as far as it will go, and twists it back and forth to gather fluid and cells.
For Bluemke, it seemed like 10 seconds on each side.
“A test I hope I never have to have again,” he said.
One Utah teenager recently described it on the TikTok online social networking platform as feeling “like being stabbed in the brain.”
That’s sort of true.
“It’s like a brain biopsy to get a good sample,” said Dana Hawkinson, director of infection prevention and control at the University of Kansas Health System. He was only half joking.
“If they don’t hurt, it didn’t work,” chief medical officer Steve Stites added.
Some screeners may be reluctant to cause that much pain and not get a proper sample. Due to a lack of the proper kind of swabs, some screeners are making do with substitutes and not always with good results. That shortage has some turning to 3-D printing to make their NP swabs.
Then there’s timing. If the specimen is collected early in the course of the disease, before enough cells have reproduced, the lab won’t detect them. Same if the disease has progressed beyond a certain point.
The samples also must be analyzed within 72 hours of collection or they’re invalid.
Stites and Hawkinson say KU has been pleased with the accuracy of its COVID-19 testing.
But the research out of China showed numerous instances where the nasal swab test failed to detect the infection, which was then confirmed with CT scans that showed white patches in patients’ lungs, called ground-glass opacity, indicating that the disease had taken hold.
Chinese researchers said in an article in the Journal of the American Medical Association that it was easier to find evidence of the disease in fluid that had been washed out of the lower lung and coughed-up phlegm. Indeed, the Chinese doctor who came under criticism from the communist government for raising concerns about the epidemic there tested negative several times for the virus before testing positive.
He died from COVID-19.
Antibody tests coming
Latinis said his own concerns about false negatives arose after two nurses he works with got sick last month.
They experienced flu-like symptoms after coming in contact on March 23 with a man who was later diagnosed with COVID-19.
One of them, a 25-year-old certified nursing assistant from Peculiar, Missouri, said she began feeling feverish a week after visiting the clinic where she was working. Her temperature rose to as high as 103, Latinis said. After testing negative for flu and strep, she was initially denied a test for COVID-19, but got one after Latinis insisted and got approval.
The sample sat at the Cass County health department for nearly 24 hours, because it got there too late for the daily courier pickup to the state lab in Jefferson City. And then due to a backlog, it almost wasn’t tested before the 72-hour time limit expired.
She got the results a week ago Thursday. Negative.
But because the Peculiar woman still wasn’t getting better, Latinis began familiarizing himself with the research on coronavirus and false negatives.
She’s feeling OK now, and would like to go back to work next week, she says. But she wants to make sure she won’t infect anyone and worries that she’ll be stigmatized if co-workers and the people she cares for know she was exposed to the virus.
For that reason, she asked that her name not be published.
“I work with older patients who have COPD and asthma,” she said.
They need not worry, as it turns out. On Thursday, Latinis got ahold of some rapid blood tests that, with a finger prick, can tell whether a person has had COVID-19 by detecting antibodies in the blood.
He did her test and a couple of others Friday morning because he wanted to see whether his hunch was accurate.
In her case, it wasn’t. The Peculiar nurse had gotten sick from something nasty, but it wasn’t COVID-19.
“This surprised me,” he said, “but nonetheless sheds light on how important testing on the backside with these antibody tests is going to be.”
On Friday, Fauci told CNN that “a rather large number” of those blood tests will become available, allowing us to better know who is protected from the virus, and who is not.
“As we get to the point of at least considering opening up the country, as it were, it’s very important to appreciate and to understand how much that virus has penetrated this society,” Fauci said.
“Because it’s very likely that there are a large number of people out there that have been infected, have been asymptomatic and did not know they were infected.”
This story was originally published April 12, 2020 at 5:00 AM.
