How false negatives complicate COVID-19 tests

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Washington (AFP) – As COVID-19 tests become more widely available in the United States, scientists have warned of growing concern that many people with negative results may actually have the virus.

This could have devastating consequences as a global recession looms and governments grapple with the question of when to reopen closed economies when billions have been ordered to stay at home in an attempt to break transmission of the deadly disease.

The majority of tests around the world use a technology called PCR, which detects lumps of the coronavirus in mucus samples.

But “there are a lot of things that affect whether or not the virus is detected,” Priya Sampathkumar, an infectious disease specialist at the Mayo Clinic in Minnesota, told AFP.

“It depends on how much virus the person clears (through sneezing, coughing, and other bodily functions), how the test was collected, and whether it was done properly. by a person accustomed to collecting these swabs, then the length of time it was transported, “she said.

The virus has only spread to humans for four months, so studies on test reliability are still considered preliminary.

Early reports from China suggest that his sensitivity, which means how capable he is of returning positive results when the virus is present, is around 60 to 70%.

Different companies around the world now produce slightly different tests, so it’s hard to have an overall figure.

But even if it was possible to increase sensitivity to 90%, the magnitude of the risk remains significant as the number of people tested increases, argued Sampathkumar in an article published in Mayo Clinic Proceedings.

“In California, it is estimated that the COVID-19 infection rate could exceed 50% by mid-May 2020,” she said.

With 40 million people, “even if only 1% of the population were tested, 20,000 false negative results would be expected”.

It is therefore essential for clinicians to base their diagnosis on more than the test: they should also examine a patient’s symptoms, potential history of exposure, imaging, and other laboratory work.

– Timing is everything –

Part of the problem is in locating the virus because its area of ​​highest concentration moves around the body.

The main nasal swab tests look at the nasopharynx, where the back of the nose meets the top of the throat. This requires a trained hand to perform and some of the false negatives come from an incorrect procedure.

But even if done correctly, the swab can still produce a false negative. In fact, as the disease progresses, the virus passes from the upper respiratory tract to the lower respiratory tract.

In these cases, the patient may be asked to spit sputum – mucus from the lower lungs – or doctors may need to take a more invasive sample when a patient is sedated.

Daniel Brenner, an emergency doctor at Johns Hopkins Hospital in Baltimore, described a test to AFP after performing a procedure called bronchoalveolar lavage.

This was done on a patient whose nasal swab returned negative three times, but who showed all signs of COVID-19.

Finally, the patient’s medical team placed a camera on his trachea to examine the lungs, then sprayed fluid and aspirated the secretions, which were then tested, which gave a positive result.

– No perfect test –

Uncertainty in clinical diagnostics is not new, and clinicians are well aware that no type of test for any condition can be considered perfect.

What makes COVID-19 different is its novelty, said Sampathkumar.

“Most of the time, when you have tests, you have carefully described test characteristics and warnings about the interpretation of the tests,” she said.

“We haven’t had a test in so long, and when we got it, we started to use it extensively and somehow forgot the basics. “

After taking a long time to start mass testing, the United States has increased production and tested nearly 2.5 million people, with pharmacists now allowed to perform the procedure.

But “the real fear is that people will take a false negative test and then decide that they are sure to go around their daily lives and go out and expose people,” said Brenner.

Much hope is placed on newly available serological tests that look for antibodies produced by a person’s body in response to the virus and can tell if a person has been infected long after they have recovered.

They could also be used to help diagnose a person who is currently infected but whose PCR test results have shown a false negative, waiting around a week for the body to produce its immune response.

“We are excited about the serological test, but we do not know how well it will work and we are starting to study it,” said Sampathkumar.

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