To safely relax the chokehold that policies to control Covid-19 have on the economy, most experts agree that the U.S. will need a four-pronged strategy: aggressive diagnostic testing for the disease, isolation of known cases, tracing of their contacts, and quarantining of anyone who might have been exposed until they are clearly uninfected. Many public health officials have focused on the challenge of contact tracing, saying it will require “an army” of new workers.
In fact, however, the re-opening effort is in danger of failing spectacularly because the U.S. hasn’t gotten the first and last steps right — which both rely on accurate diagnostic testing. The current swab tests for the novel coronavirus are missing up to 30% of infected people.
In a scramble to fix that before it’s too late, a growing number of doctors are calling for use of another method to detect Covid-19, one that would miss fewer cases than molecular testing of swabs does: chest CT scans.
CT scans are far more expensive, they expose patients to a low dose of radiation, and the Centers for Disease Control and Prevention and some medical groups recommend against using them to diagnose Covid-19. But they were widely used in China to identify cases, and their reliability there is fueling growing interest in adding chest CT to the diagnostic arsenal in the U.S.
The scans detect hazy, patchy, “ground glass” white spots in the lung, a telltale sign of Covid-19. In one recent study of 1,014 patients, published in the journal Radiology, scientists in China reported that chest CT found 97% of Covid-19 infections. In comparison, the study found that 48% of patients who had negative results on the swab test, which detect the coronavirus’s genome, in fact had the disease.
“Once you’re a couple of days into infection, chest CT scans don’t miss,” said an emergency medicine physician in Louisiana who asked not to named. With the swab test missing 30% to 50% of cases, physicians in China called for the diagnostic use of CT early in the outbreak there, and “fever clinics” set up in Wuhan and elsewhere began routinely using them.
A positive result on the swab tests is usually reliable. “If you get a positive test result, looking for the RNA of the virus with the current methods that we have, it’s very likely to be a true positive,” said Jana Broadhurst, an infectious disease doctor and director of the Nebraska Biocontainment Unit Clinical Laboratory at the University of Nebraska Medical Center. But “if you get a negative test result, [the chance that it’s wrong is] about 30%.” Of every 100 symptomatic people who test negative for Covid-19, 30 are actually infected. The test missed them.
The main reason is sample collection. The swab that’s supposed to be pushed into the back of the nose (often painfully) and then curve down into the throat sometimes doesn’t reach far enough, or doesn’t remain in place long enough, to collect a decent sample. The swab can trigger violent coughing, making the technician or nurse taking the sample pull back too soon. “We have a mantra in the lab,” Broadhurst said: “Garbage in, garbage out.”
Because the fault is human rather than molecular, there is no technological fix. If tests are the first leg of an exit strategy, as the Johns Hopkins Center for Health Security said in a plan released last weekend for reopening the U.S. economy, then incorrectly “clearing” 30% of those who are tested will doom any exit plan. They could be cleared to return to work when they’re actually infectious, and — even worse — those they encounter and potentially expose to the virus would not be identified and quarantined.
“We cannot rely fully on the test” to guide decisions crucial to re-opening the economy, said Sandro Galea, a physician and epidemiologist who is the dean of the Boston University School of Public Health.
The alarming rate of false negatives from molecular testing, as well as the often dayslong wait to receive results, is driving more and more medical centers to adopt CT scans for Covid-19 testing. They include Mount Sinai in New York City, Bloomberg reported, and a growing number of physicians across the country.
Last week the Fleischner Society, an international group of chest radiologists, broke with the CDC and the American College of Radiology, which recommend against chest CT to diagnose Covid-19. The Society concluded that it can in fact be appropriate in some situations, including a pandemic.
“Every ER physician I know recognizes the power of these scans,” said Joseph Fraiman, an emergency medicine physician at hospitals in the New Orleans area who does two or three chest CTs on suspected Covid-19 patients every shift. “Aggressive disease identification would involve both [swab tests] and CT to ensure the highest sensitivity, missing the fewest cases possible.”
But despite China’s experience, the use of chest CT to diagnose Covid-19 in the U.S. remains very limited (no one has data on how many have been done). That’s due in large part of the CDC and the American College of Radiology recommendations.
One of their objections is that CT scanners will become contaminated with the coronavirus. China, whose fever clinics routinely scanned 200 patients per day per machine, managed to clean the machines between patients well enough to avoid infecting health care workers or subsequent patients, however. Researchers there reported last month that CT scanning is far safer for health care workers than the swabs that reach the throat via the nose, and often trigger explosive coughing that can spew virus particles into the air. Thanks to staff training and between-patient scanner cleaning, after 3,340 CT scans for suspected Covid-19, another group of physicians in China reported, “none of the staff of the radiology department was infected with Covid-19.”
“It’s not like China has a monopoly on the technology to clean CT scanners,” said the Louisiana emergency medicine physician who asked not to be identified, so as not to anger colleagues. “Are you really going to say that your cleaning protocol is why you’re willing to kill 1 million people?” if the test/isolate/trace strategy fails because of faulty swab tests.
Fraiman said he is able to do chest CTs for his suspected Covid-19 cases by getting the technicians and cleaning crews on board: “I tell them, you are the guys who are going to save us!”
Another objection is that CT scans cannot easily distinguish between Covid-19, SARS, MERS, and other viral pneumonias, including from influenza. “They’re not specific enough,” said Sanjat Kanjilal, an infectious disease physician at Brigham and Women’s Hospital in Boston.
Although SARS, which is caused by a coronavirus related to the one causing Covid-19, was eliminated, and MERS (also from a coronavirus) is extremely rare outside the Middle East, viral pneumonia looks a lot like Covid-19 in a chest CT. “That makes me skeptical that it can have a big role to play,” Kanjilal said.
Although CT scans can misidentify other viral pneumonias as Covid-19, said radiologist Paras Lakhani of Thomas Jefferson University Hospital in Philadelphia, the chances of that are much lower outside of flu season, which is ending. Reading scans during a time of year when flu and therefore pneumonia is rare, he said, “would give us more confidence in interpreting a scan.”
Also increasing confidence are artificial intelligence add-ons being developed to reduce how often the scans mistake other pneumonias for Covid-19. Those systems have yet to prove themselves, but “radiologists are becoming better at interpreting chest CTs in potential Covid-19 patients, since we’re seeing more and more of them,” Lakhani said.
Even a false positive rate of 30% is less problematic than false negatives, argued Fraiman, who before Covid-19 gave “grand rounds” talks to hospital physicians warning against the overuse of CT. That’s because the consequences of telling someone she has Covid-19 when she actually has the flu are not like telling someone she has cancer when she doesn’t: The advice is simply to self-isolate (a good idea for flu patients, too), not undergo dangerous surgery or other treatment.
“Doctors need to think about false positives differently in the context of a pandemic,” said Fraiman, the former medical director for Louisiana’s disaster preparedness committee. “Reducing false negatives can prevent additional cases and deaths. The false positives seem like a small price to pay for that.”
To be sure, chest CTs are no panacea. They, too, can miss Covid-19 cases; just two-fifths of the Diamond Princess passengers who had positive swab tests had lung opacities, researchers reported last month.
“There is evidence that a large fraction of Covid-19 patients have normal CTs,” said radiologist Mark Hammer of Brigham and Women’s Hospital in Boston. “Using CT to screen patients would let a lot of people go who may be infectious.”
Absent more accurate Covid-19 tests of any kind, whether swabs or CT or a combination, states’ tentative “re-opening” plans will be inefficient at best and failures at worst. The many Covid-19 cases that swab tests miss, said BU’s Galea, “is why the proposed Massachusetts contact tracing plan I have seen will quarantine people for 14 days even if they test negative” — a fortnight that someone could have been safely back at work and in the community if only a negative result on the molecular tests were more credible.
Like many others, however, Galea questions whether “something as resource intensive as CT scans can ever be an effective population-wide screener.” He calls it “implausible” but “not impossible.”
The reason for cautious optimism is that 80 million CTs were performed in the U.S. last year. “The country has a lot of scanners, especially in outpatient settings,” Jefferson’s Lakhani said, and in urban and rural areas alike.
It’s not clear how many Covid-19 cases testing can safely miss without sinking re-opening strategies that hinge on testing and contact tracing, said Hopkins’ Crystal Watson, a co-author of the “re-opening” road map. “I think we need to find the vast majority of cases,” she said — based on the experience of South Korea, upward of 90%. “False negatives are going to be a problem and could definitely undermine” re-opening hopes.
This story has been updated with additional expert comment.