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A review of the "rapid antibody tests" has shown that they produce too many false negative and false positive, according to WHO Image Credit: Agency

Dubai:"False negative" is a term that's been in the news lately. In Dubai, health authorities have cracked down on the use of "rapid antibody tests" for COVID-19 due to the high rate of false negatives which the tests yield.

A false negative simply means you test negative even if you actually have it. It means then that some of the tests on the market are not worth anything. One brand bought by an Indian government agency from a Chinese manufacturer was found to 145% overpriced — it was originally sold for $3 apiece, despite its being unreliable.

It's no surpise that the fuzzy record of such "rapid antibody test" kits has created confusion among frontliners and patients. One undesirable result is that it could actually lead to spike in virus transmission, say experts.

The WHO, which conducted a review of such tests, said when rapid antibody tests produce too many false negative and false positive results, it renders them useless.

In the US, the Food and Drug Administration (FDA) had also cracked the whip on test makers as independent evaluations of their products’ performance show a need for improvement.

Rapid antibody test kit: What is it?

It's pregnancy-style rapid anti-body testing kit. It uses blood samples of a patient (also known as "serology") to detect the presence of antibodies in general.

In theory, it allows health professionals to know whether or not you have developed immuno response to the virus. Knowing this allows them to respond properly, allowing them to better understand the transmission, characteristics and knowing how many individuals have actually been infected versus those who may have not developed symptoms.

An at-home COVID-19 antibody rapid test cassette. Bloomberg
An at-home COVID-19 antibody rapid test cassette. Bloomberg Image Credit: Bloomberg

Dozens of antibody tests for immunity to COVID-19 have been release onto the market

Also in theory, those who are confirmed to have developed antibodies for SAR-CoV-2, may be good candidates to donate blood plasma which can then be given to sick individuals suffering from COVID-19.

But in practice, it's a different story.

What happened before with such rapid antibody tests?

In general, its use can be indicative of an immune system being developed. Experts have seen that using the rapid antibody test to detect SARS (which appeared on 2002-03), protective immunity was present in those who recovered for about two years, according to Elitza Theel, director of Mayo Clinic's Infectious Disease Serology Laboratory.

She also cited studies done in monkeys showing they have at least short-term immunity of one month after recovery from sARS-CoV-2. 

She cited, however, since the new virus has appeared only recently, there's a dearth of scientific data on long-term immunity to it. She further added that there's still no evidence to conclude on the effectiveness of serology test, or rapid antibody test, especially on the question of effective duration of immunity from SARS-CoV-2 reinfection.

What is a false positive?

In short, it's the reverse of a false negative.

Moreover, it may also show a person to have the antibodies — thus potentially also immunity — and they don't, explained Prof. Emily Troemel, of UC San Diego Division of Biological Sciences.

With test kits available in the global market, which didn't go through the rigors of evaluation by regulators, and their lack of specificity for the novel coronavirus, a patient may be test positive, when the antibody detected in their blood was kicked up as a result of the presence of another pathogen, not SARS-CoV-2.

False Positive
Problem with false positives: Accuracy of serology test is also very important if true positives are rare in a population. Even if a false positive rate is just 1%, and there's just 1 true positive in a population of 100, then it would mean an accuracy of 50 Image Credit: University of California in San Diego

What is the margin of error of the rapid antibody test kits out in the market?

It's been generally between 15 to 30 per cent, according to studies. Experts argue that it's a huge margin, which makes them in effect unreliable. Also the point in the infection during which the test had been done is a key determinant of its reliability.

Why were they approved in the first place?

The Scientist stated that because of the nature of this novel coronavirus, the US Federal Drug Administration (FDA) approved the tests under the Emergency Use Authorisation scheme.

The objective was to not only develop tests capable of detecting the virus but also to mass produce them and get them into the hands of frontline healthcare workers quickly.

Due to the urgency of the situation, the FDA granted approval for the tests without having to go through the rigorous testing that would ordinarily be required.

Why is rapid antibody test unreliable?

As stated above, the science behind it, especially as applied to detecting SARS-CoV-2, is still in its infancy, as is the medical fraternity's understanding of the virus itself.

Although some of the test kits claim "97-99 per cent sensitivity", it's just a claim. And even if true, the test is still not specific to the new coronavirus. That means an antibody may be detected in your blood (in which case it's a "false positive" result), though it may not necessarily be due to SARS-CoV-2 infection.

With a false negative result, it would mean those who are in fact positive may be released in the community, thus spreading the virus unnecessarily, instead of taking proper preventive measure.

Moreover, patients admitted to the hospital for unrelated reasons might still be carrying the virus. If they are incorrectly determined not to have the virus (false negative), then they could pose a risk to other patients in non-COVID wings, furthering the spread of the virus.

SENSITIVY VS SPECIFICITY
Lab tests are characterised by their ability to detect a positive case (sensitivity) and their ability to determine a negative case (specificity).

So a sensitive test is less likely to provide a false-negative result. A specific test is less likely to provide a false-positive result.
PCR 3
Image Credit: Gulf News / Jay Hilotin

Is the rapid antibody test kit banned for use now in Dubai?

Yes. On Wednesday (May 13, 2020), the Dubai Health Authority (DHA) banned the rapid viral test for COVID-19 for being unreliable and causing confusion.

In a circular, DHA ordered all private hospitals, outpatient care facilities and pharmaceutical establishments to refrain from using or selling the rapid viral anti-body testing kits.

'Analytic' sensitivity and specificity of a test
In describing a test, test kit manufacturers usually refer to “analytic” sensitivity and specificity. They are based on the analysis of a set of known positive and negative samples.

But numbers often show the accuracy of a test under ideal conditions — when samples have been collected from patients with either high viral loads or a complete absence of exposure.

Real-world conditions when taking specimens are often less than ideal.

Sensitivity and specificity in situations in which patients are more variable and specimen collection may not be ideal, can often be lower than reported numbers.

How many types of tests are there for COVID-19?

In general, there are two types:

(1) Rapid antibody test, also known as serology test. It uses a patient's blood as sample to detect the presence of antibodies in the blood — and yields relatively quick results, typically within a few minutes.

  • Measures current and past infections
  • Antibodies do not necessarily prevent re-infections

(2) The RT-PCR uses a nasal or throat swab to detect the presence of specific genetic markers of the SARS-CoV-e virus in the sample.

  • More reliable and highly accurate.
  • Time consuming, complicated to perform, expensive.

The RT-PCR technology has been around for a long time. The RT-PCR test itself only takes about a day. With thousands of requests for PCR tests and with limited time and staff — and logistical challenges (i.e. the need to ship samples to labs), it may take most patients days, or even weeks, to get their results back. The UAE has solved this problem by establishing drive-thru PCR test centres across the country.

PCR 01
Image Credit: Gulf News / Jay Hilotin

What are antibodies?

An antibody, also known as an immunoglobulin (iG), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as pathogenic bacteria and viruses.

Antibodies are the so-called "soldiers" that are naturally produced in the blood in response to a viral or bacterial exposure.

What is the problem with the use of rapid antibody test kits?

There are two issues involved in the use of such test kits.

The first is the timing of use. Since antibodies usually develop after 5-7 or more days following exposure to a pathogen (disease-causing bacteria or virus), the rapid antibody test kits are not advisable for early detection.

The second is the quality of manufacture of the kits themselves.

How many brands of rapid antibody test kit have been released in the market?

There are dozens out in the market around the world. Most of them have had little regulatory oversight. Which means, they may be unreliable.

Regulators in the US, such as FDA and CDC have announced moves to better regulate the tests, but they did not state what level of accuracy they might consider sufficient. Not all manufacturers of these antibody blood tests have released data on their products’ sensitivity and those who claim high sensitivy or specificity cannot be immediately validated.

Even the tests for which data are available might simply not be good enough.

Currently, there are at least 29 commercial tests (assays) on sale in America designed to detect antibodies to the coronavirus, data compiled by EvaluateMedTech show. Here's the link to the list of tests granted FDA backing in the form of an "emergency use authorisation" (EUA).

But none of these tests, even those with EUAs, have had their accuracy evaluated thoroughly by the FDA or any other regulatory body. Most manufacturers make their own unverified claims for accuracy.

What test is approved for use in the UAE?

The UAE has established COVID-19 drive-through test centres, with 14 locations in the country, the largest laboratory network in the world outside China.

Using industrial-scale RT-PCR technolgy, the UAE has ramped up testing for COVID-19. As of May 13, more than 1.5 million tests had been done across the country, ranking the UAE among the highest in the world in terms of screening per capita. 

Seha drive through
Drive-through COVID-19 screening centre in Abu Dhabi. Image Credit: Seha

The first such laboratory was built in just 14 days in Abu Dhabi, fitted with state-of-the-art diagnostic equipment to boost response to and containment of the virus.

Citizens and residents can also get tested at many hospitals and specialist health centres. People are advised to take a prior appointment before going for a hospital or for drive-through test.