This article is not about the problems with testing that we all know about: it started too late, there was a problem with accessibility, it took too long to get results, there was a shortage of swabs, a shortage of testing centers, long lines, and many delays – but rather, it’s about another problem you may not be aware of: accuracy.

When you get any medical test, you want to have complete confidence that the results are accurate. You don’t want to be told you have cancer if you really don’t, or told you’re not pregnant when you really are. This is why tests have to go through a rigorous approval process by the FDA. No one wants false positives or false negatives.

We tend to think that the governmental approval process is overly long, laborious, and not justified… especially when people are sick and lives are at stake! We were glad when the FDA gave swift approval (even if only a provisional approval) to a variety of Covid-19 tests. But should we be?

Sampling

Tests are now available from different commercial and academic labs – some for detecting the virus (active infections) and others for detecting antibodies (revealing you’ve been exposed). For virus detection, most of these tests use samples from the nose, throat, or more recently, saliva. Studies have shown that active virus can be found in a variety of bodily locations (even feces), at different times, and in different people. A bronchoalveolar lavage yields the most reliable results (93% accurate) but is quite difficult to obtain: it requires placing a bronchoscope into your lungs which would be a surgical procedure.

No one body site is 100% reliable in everyone, but of the least invasive sites, the nose has the highest probability of giving reliable results and samples can be obtained readily without sophisticated instrumentation and risk. That’s why most diagnostic tests use nose swabs.

Reliability of Nasal Swabs

On average, the virus is found in nasopharyngeal samples about 72-73 percent of the time in actively infected people. That means in the 27-28 percent of the tests that come back negative, a portion of those patients could actually be positive but are shedding the virus from another bodily site. Getting a false negative means you could be spreading the virus to others unknowingly. Here are a few other reasons you can get a false negative result from your nasal swab:

Collection Technique: The correct way to obtain the sample is to place the swab all the way up the nose to the very back and turn it over and over, scraping the back of the nasopharynx. If you’ve had it done right, it should hurt and feel like they must’ve sampled your brain.

Many technicians are afraid of hurting you and so do not go far enough up the nasal canal. You will likely get a negative result if you just sample from the bottom end of your nose.

Timing: The virus is only active in the nasopharynx for a short time – maybe 7 days. If you got sampled too early in your illness or too late (after the illness has moved into your lungs), you may no longer have enough virus in the nose to yield a positive result.

Sample Degradation: The virus will only be viable on the swab at most 8 hours at room temperature or 72 hours with refrigeration. Many testing sites were in parking lots and samples were kept outside, gathered up at the end of the day, and then transported without being on ice the entire time (or the ice may have melted).

Once the sample gets to the lab, the sample may sit for many days – hopefully in a refrigerator - before the test is run due to the labs being so backlogged.

I know people who did not get results until 12 days later. By then, the sample surely would have deteriorated and so it is not surprising that it yielded a negative result. Sample degradation due to poor conditions during storage and transport was responsible for 1,043 tests in Alabama being invalidated.

Are the Rapid Tests Better?

There is a new crop of COVID-19 tests that can give more rapid results, in about 15-30 minutes. Reports of the sensitivity of these tests are 34-80 percent, meaning that of the 20 percent or more that are negative, a portion of those may actually be positive. Plus, since the rapid tests use the same type nasal swab, they would be subject to the same errors of sample collection, timing and degradation explained above.

Approval Process is Suspect

The U.S. was late to start testing. Consequently, there was great pressure to greenlight any tests quickly to make up for the late start. Rather than the typical approval process involving thousands of real-life samples correlated with actual clinical outcomes, approvals were given for “emergency use” (called EUA) or other provisional status.

Each lab seeking approval was given 60 samples (30 known positives and 30 known negatives) which the lab had to score with 95% accuracy. But the samples they were given were not real-life samples from the nasal swabs from real patients. They were lab-made samples containing portions of the Covid viral RNA and a “medium simulating nasal mucus.” Although a lab can tweak their assay to score these test samples correctly, it bears little resemblance to the accuracy with which the lab’s assay can detect COVID-19 in real patient samples.

To be fair, no test is 100 percent accurate, even those that are subject to the full-fledged FDA approval process. But fast-tracking the current crop of COVID-19 tests means there has been little reconciling of the test results with the clinical patient data, few stringent studies, and known flaws. It is estimated that about 10-25 percent of all negative test results are actually positive. Knowing this, they tell patients that even if you get a negative result, you should still act like you are infectious and stay away from others, wear a mask, and so on. If that’s the case, why get tested to begin with?

Are Antibody Tests Better?

Antibody tests use the patient’s blood – called serological testing – and not nasal swabs. Its purpose is to detect if you had the disease at some point in the past, whether you knew you had the disease or not. An antibody test cannot tell if you are actively infected because it takes 2-3 weeks after you get the disease for your body to build up enough antibodies in your bloodstream to be detected by the test.

By then, you’re likely over the illness. If you have antibodies, you are immune to another bout with COVID-19 which is why they want to use antibody tests to determine if you are “safe” to go back to work. Even asymptomatic COVID-19 subjects will have antibodies, so widespread antibody testing can tell us the real number of people who actually had COVID-19 as well as how accurate the patient’s test result might have been (for those who had one of those tests). But, here are some problems with the antibody tests:

Unregulated: The antibody tests have been subject to same speedy approval process as the tests for detecting active COVID-19 infections (discussed above) but even more so. This is because they use similar techniques to existing antibody tests for similar viruses already on the market, so lots of the scrutiny has been “grandfathered in.” The approval of antibody tests has been dubbed the “Wild West’ of unregulated tests.

Detection: Antibody tests work by detecting the virus’s genetical material. Since all coronaviruses have a large portion of genetical material in common, they could yield positive results not just for Covid-19, but also for other corona viruses. This means, due the design of the test, it is easy for the test to give false positive results. Thus, you may think you have antibodies to Covid-19 when in fact you have antibodies to the common cold, another type of corona virus.

Significance: Just because a person has the antibodies and is no longer ill, we do not know whether the person can still spread the disease and be a carrier. There have been reports of people who had gotten over the illness but still were getting positive tests 28 days later, and people who got positive tests weeks after getting a negative test. At this point, we do not know whether this says more about the inaccuracy of the tests themselves or whether we still don’t know enough about the lifecycle of this virus.

Duration: Antibody levels tend to drop off after a period of time. This is why it is recommended that you get a tetanus vaccine every 10 years, because your immunity wanes over time. For Covid-19, we do not know how long immunity will last nor what level of antibody is required to confer immunity. It is believed that the period of immunity is at least a year or two, but this has been based on animal models, not humans.

The Hype

Every time a commercial company announces a new test, a faster test, a better test, etc., their stock soars. A mention by the President in a press conference of one of these test-making companies is worth millions. The economic slowdown is not hurting everyone! Abbott and many other pharmaceutical and medical device companies are making out like bandits. And they didn’t have to put very much effort into the pre-market approval due to the fast-tracking of their tests, so their development costs were fairly low.

State governments, HHS, CDC, and FEMA are buying these tests as fast as the manufacturers can make them. Even if the test gives false positives and false negatives, we look the other way because we’re so desperate to have something to help us deal with this crisis.

What’s the Real Harm?

If a person is tested for active infection and gets a false negative test, they will go on to spread COVID-19 to others because they will be less cautious, not wear a mask, go back to work, tell someone it’s okay to get close to them because they’ve been tested and are negative. Those getting false negative results (but are really positive) are not counted among the COVID cases. If they die, they are not counted as a COVID-related death. When being treated in a healthcare setting, the caregiver may not be wearing the right protective equipment.

If a person gets an antibody test and gets a false positive, they will think they are immune to COVID-19 when they are not. They may be cleared to go back to work, they will be more risky in their behavior (forget about obsessive hand-washing, etc.), and will wind up acquiring the disease, spreading it, and it may be life-threatening to them or the people they spread it to.

Bottom Line

The WHO (World Health Organization) recommends that no one test should be considered definitive. In fact, they consider these tests as “research grade” only. They recommend multiple tests and correlating it with the clinical symptoms.

My tip is that everyone should always act like they have the virus, regardless of what the tests say… at least for now. At some point in the future, the data will be further analyzed, and hopefully the poorer tests will fall from the market.

Better yet, a reliable vaccine will be developed, eliminating the need for widespread testing. Then, we’ll need widespread vaccination, and that’s another story. Let’s hope they don’t fast-track the vaccine so much that it is as worthless as the tests.