Rapid Antigen Tests Cannot Distinguish SARS-CoV-2 and HKU-1 - and That's Dangerous

FDA Documents Show They Are Not Specific. The Law of the Instrument Tells Us That's a Big Problem.

There’s an old expression: “When you’re a hammer, everything looks like a nail”. Sometimes referred to a "Maslow’s hammer”, this expression captures the idea of the law of the instrument. The origin of the expression seems to be from the observations that if you give a boy a hammer, they start pounding away at everything. Wikipedia has a good page on the history of this expression.

Thank goodness that regulations require that the FDA EUA documents not only be submitted, but that they can be viewed and read by anyone with access to the internet or who write to the FDA for a copy.

Everyone testing with the BinaxNOW nasal swab test, for example should be aware that per the documents provided by Abbott to the US FDA, their test can be a false positive if the person is infected with the HKU1 virus. (See the IFU Document):

“The comparison between SARS-CoV-2 nucleocapsid protein, MERS-CoV and human coronavirus HKU1 revealed that cross-reactivity cannot be ruled out.”

This language (or similar) is found in other IFU Documents for other COVID-19 RAT tests as well.

That means the test lacks pathogen specificity, and FDA cannot tell us what the risk of a false COVID-19 indication is without follow-up PCR testing. Further, like the PCR test, the comparison was only computational, based on BLAST-determine homology, not based on studies of thousands of patients. Further, protein structure, not sequence, is important for cross-reactivity - BLAST is not refined enough a tool to determine actually binding capacity, yet the FDA allowed negative BLAST results as evidence of degree of specificity.

PCR testing is similarly fraught with its own false positive problems, in part due to the same error (allowing BLAST results instead of requiring actual data from large studies). This is an issue the CDC could be finally coming to terms with after IPAK published a peer-review study in our journal on the problem, after Dr. Sin Hang Lee published two studies, after dozens of videos and articles have been written by yours truly alerting the world of the problem of PCR false positives due to the use of high cycle thresholds, and after an uproar over the fact that the PCR tests do not rule in Influenza.

HKU1, aka HCoV-HK1, first detected in 2004 in Hong Kong, is a Betacoronavirus (because it has a Hemagglutinin esterase gene), and enters the cell via a different recept that SARS-CoV-2. Like SAR-CoV-2 and SARS-CoV-2, it is an enveloped, single-stranded RNA virus.

Here’s an array of symptoms of HKU1 infection reported in 2017:

“Of 832 adult respiratory specimens screened, 13 (1.6%) cases of CoV-HKU1 were identified. Adults age ranged between 23 and 75 years and 6 (46%) were males. All of whom had 1 or more respiratory symptoms, and 5 (38%) also reported 1 or more gastrointestinal symptoms. Eleven (85%) reported history of smoking and 5 (38%) used inhaled steroids. Seven (54%) required hospitalization, 5 (71%) of these needed supplemental oxygen, and 2 (29%) were admitted to intensive care. Median length of hospitalization was 5 days. Eight (62%) received antibiotics despite identification of CoV-HKU1. Infectious work-up in 1 patient who died did not reveal any other pathogen. In 2 (15%) CoV-HKU1-positive adults, the only viral coinfection detected was influenza A.”

In 15% of people studied, co-infection with Influenza A was detected. That’s fairly common. For all of 2020-2021, for two years, “co-infection” of COVID-19 patients (PCR+ for SARS-CoV) was not even mentioned. Now that everyone (well, nearly everyone) is testing with in-home nasal swab kits for antibodies, many will be positive but will actually be HKU-1. Given the FDA’s allowance of specificity-by-BLAST, the problem could be much worse.

Why This is Dangerous

There are few good reasons why this is dangerous. Yes, the problem will make it appear as if more people have COVID-19 than actually do. The clinical workflow for COVID-19 is far more strenuous than for influenza A or HKU-1, so there’s the added burden on the healthcare system. I’ve heard reports that some hospitals are resorting to triage, placing non-PCR+ non-respiratory illness patients at risk (the in-hospital PCR screening adds to this as well).

However, people who have had a positive Rapid Antigen Test may also come to think of COVID-19 as mild for them, and their families - and worse - they may believe they have natural immunity and let their guard down. They may be more willing to attend a large gather, or mingle with others while symptomatic.

Third, false positives from PCR and from RAT tests alike will lead the public - and public health and medical communities - to believe that re-infection with SARS-CoV-2 is possible. The dynamics of societal responses will be flawed, leading to more quarantine, shut-downs, draconian control measures.

Fourth, the clinical care for a person who has respiratory viral infections other than SARS-CoV-2 may be different. If 15% of patients with “COVID-19” have something else, the CDC should know and medical practice should be altered to address this.

Fifth, co-housing non-COVID19 respiratory patients with COVID-19 patients can place them at risk of SARS-CoV-2 infection. Being sick already, they may have a more difficult clinical course as a result. Here’s a case of a woman who had HKU-1 infection on the day of entry and tested positive for COVID-19 on Day 3 of hospitalization.

Every single person who tests positive via PCR or RAT who has clinical symptoms or who has been exposed to a confirmed case of COVID-19 should have a confirmatory Sanger Sequencing test conducted to ensure what they have (or had) was truly a SARS-CoV-2 infection. As an added benefit, unlike PCR or RAT, Sanger Sequencing can tell us what variant we have (or have had).

There are over 6,000 laboratories around the US that can conduct Sanger Sequencing, and Sin Hang Lee, MD of Millford, CT is happy to provide the information on the primers he has developed for nested primer target amplification - and for Omicron detection.

Here’s a requisition form that can be used to order the Sanger Sequencing test (I have no financial relationship w/Dr. Lee or Millford Diagnostics).

The Law of the Instrument tells us that if you only test for COVID-19, you’ll only find COVID-19. Multiplex respiratory pathogen tests are also used in some places.

Please share with doctors and nurses in your area. This could help you & your loved ones travel a safer course.