How Accurate and Reliable is COVID-19 Testing?
By: Nita Jain
Tags: Health, Education, Science, Ideas, Covid 19

COVID-19 / MEDICINE / HEALTH

How Accurate and Reliable is COVID-19 Testing?

PCR-based nasal swab testing and serological antibody testing both have certain limitations.

As more and more state health departments and private enterprises continue to ramp up testing capacity for COVID-19, several health experts warn that test results are not 100 percent accurate and should be interpreted in the context of clinical presentation and exposure risk.

The most commonly used PCR-based nasal swab test to detect SARS-CoV-2 is highly specific but not very sensitive, meaning positive results are more useful than negative results. In other words, a positive result almost guarantees infection with the novel coronavirus but a negative result cannot rule out the presence of infection.

“The issue with the tests for the SARS-CoV-2 virus is that there has not been time to test them rigorously before deploying them in the field,” says Dr. Gary L. LeRoy, president of the American Academy of Family Physicians.

“Most polymerase chain reaction (PCR) and antibody tests have years of laboratory testing before they are used. We just don’t have that kind of time. The major concern for false negatives is someone who tests negative, thinking they are not infected, could unknowingly spread the virus into the community.”

Healthcare worker administers nasal swab test for COVID-19 at a drive-thru facility (Photo by Zstock)

An article published in Mayo Clinic Proceedings draws attention to the risk posed by over-reliance on COVID-19 testing to make public health decisions. Priya Sampathkumar, M.D., an infectious diseases specialist at Mayo Clinic and study co-author, writes that healthcare officials should anticipate a “less visible second wave of infection from people with false-negative test results.”

Based on preliminary evidence from China, quantitative reverse transcription polymerase chain reaction (qRT-PCR) COVID-19 testing on nasal swab samples may produce false negatives up to 30% of the time when testing is conducted 0–7 days after illness onset. After 15 days of illness, the chance of receiving a false negative result shoots up to 50%.

That false negative figure may be even higher in the US, according to Harlan Krumholz, M.D., a professor of medicine at Yale. In an opinion piece for The New York Times, Dr. Krumholz expounds:

“There are many reasons a test would be falsely negative under real-life conditions. Perhaps the sampling is inadequate. A common technique requires the collection of nasal secretions far back in the nose — and then rotating the swab several times. That is not an easy procedure to perform or for patients to tolerate. Other possible causes of false negative results are related to laboratory techniques and the substances used in the tests…If you have had likely exposures and symptoms suggest Covid-19 infection, you probably have it — even if your test is negative.”

Nasal swab sample for COVID-19 test in the laboratory (Photo by Robert Kneschke)

Dr. Alain Chaoui, head of Congenial Healthcare, a practice with 50,000 patients across five locations in Massachusetts, told The Boston Globe, “A lot of my patients who have symptoms, who I clinically think have COVID-19, are testing negative.” Chaoui is nonetheless advising all his patients who test negative for the virus to assume they are infected and self-quarantine until symptom-free for at least 72 hours.

Michelle Taylor tested negative for COVID-19 twice despite presenting with concerning symptoms, including loss of taste and smell. Several doctors have said the long swabs inserted deep into a patient’s nose could miss the virus if the patient is not showing many symptoms at the time of the test. Dr. Paul Pottinger, an infectious disease physician at UW Medical Centerm explains,

“The one caveat like we talked about before, if you go in to get tested too early — for example if you have no symptoms at all — then the test may not work very well. It’s really designed and validated for people who are having symptoms of infection when they have the test.”

According to Dr. Lee Harold Hilborne, a professor of pathology and laboratory medicine at UCLA, the high rate of false negatives may be due to improper sample collection rather than inaccurate analytical laboratory techniques. Hilborne elaborates,

“The majority of issues contributing to error in diagnostic testing are pre-analytic. These occur during specimen order, collection, and transport, before the specimen ever reaches the lab. We know that collection methods do not always pick up the virus. Studies suggest current swab collection may have sensitivity in the range of 60 to 75 percent. That means the specimen submitted to the laboratory from a patient with the infection will not contain the virus roughly 25 to 40 percent of the time.”

RT-PCR test kit to detect presence of 2019-nCoV in clinical specimens (Photo by tilialucida)

To address the risks associated with false-negative test results, Dr. Sampathkumar and colleagues outlined four evidence-based recommendations:

Continued strict adherence to physical distancing, hand-washing, surface disinfection, masking and other preventive measures, regardless of risk level, symptoms or COVID-19 test results, must be emphasized. Development of highly sensitive and specific tests, including improved RT-PCR tests and serological assays to detect antibodies, are needed to minimize the incidence of false-negative results and the risk of ongoing transmission based on a false sense of security. Risk levels should be assessed prior to testing. Negative test results should be interpreted with caution, especially for individuals in higher-risk groups, such as healthcare workers. Risk-stratified protocols must be put in place in order to properly interpret negative test results. These protocols should employ statistical data on diagnostics, transmission, and outcomes.

“For truly low-risk individuals, negative test results may be sufficiently reassuring,” says Colin West, M.D., Ph.D., a Mayo Clinic physician and the study’s first author. “For higher-risk individuals, even those without symptoms, the risk of false-negative test results requires additional measures to protect against the spread of disease, such as extended self-isolation.”

2019-nCoV IgM/IgG antibodies diagnostic laboratory test (Image by science photo)

What about blood tests to detect antibodies, the body’s response to the virus? These tests have limited utility from a diagnostic standpoint, as the body may not have had enough time to produce detectable antibodies in the early stages of infection, leading to false negative results. However, serological testing may be used to detect previous exposure, evaluate community spread, and assess antibody titers. But for now, testing results are fraught with uncertainty.

While individuals who recover from viral infections usually emerge with some degree of immunity, it is not yet known to what extent and for how long immunity to COVID-19 may last. Researchers are still unclear as to whether the presence of antibodies necessarily confers immunity to the novel coronavirus. Higher levels of antibodies generally indicates the mounting of a stronger immune response, but the levels of antibodies needed for COVID-19 immunity has not yet been established.

The reliability of antibody testing is another point of contention adding to the confusion. In Laredo, Texas, a purchase of 20,000 rapid COVID-19 tests was recently seized by the federal government after local health department officials discovered the tests were only accurate about 20 percent of the time. Generally, antibody tests that utilize a technique known as ELISA (enzyme-linked immunosorbent assay) tend to outperform point-of-care (POC) lateral flow tests in terms of both sensitivity and specificity.