Adapting to What’s Next — What You Should Know About COVID-19 Antibody Tests
Charles Darwin is often misquoted with the phrase, “survival of the fittest,” but he actually wrote, “…the fittest win out at the expense of their rivals because they succeed in adapting themselves best to their environment.” To return to any normalcy, we need antibody testing, and we must quickly adapt. Last month, I published, “Eight Ways to Smash the Coronavirus Curve.”[i] I suggested widespread testing for COVID-19 antibodies. Antibody positive individuals should have immunity against contracting and spreading the disease. Most now agree that antibody testing will help to restart our lives. But we need millions of antibody tests, and they must be reliable.
We made grave mistakes in COVID-19 testing early on in the pandemic, but we still can get antibody testing right. The FDA is the only federal agency with the power to allow release of antibody tests. During a national health emergency, like COVID-19, the usually strict rules of the FDA are waived via the Emergency Use Authorization (EUA). The EUA allows the FDA to speed up the release of treatments and testing related to COVID-19. During a health crisis, it bypasses and shortens the meticulous and slow FDA approval process. An EUA allows a company to begin selling and distributing antibody test kits with only limited paperwork and analysis. [ii] The company must state that it has a necessary COVID-19 test, and that it works. Proper validation (accuracy) must be verified on 30 recovered COVID-19 and 30 never infected patients. An EUA is not “FDA Approval,” but allows a company to sell its product quickly in this crisis.
But this minimal oversight and speed may prove to be a double-edged sword, especially when it involves companies sourcing from China.
In the past few weeks, Slovakia, Czech Republic, Turkey, Spain and the UK each purchased between 300,000 and 1.2 million defective and unusable Chinese antibody kits. The accuracy rate ranged from 20–35%. Their hasty and desperate purchases not only wasted limited funds, but cost time and lives.[iii]
Closer to home, Laredo, Texas proudly used a police escort to deliver 20,000 tests (costing $500,000) from a Chinese company, Anhui DeepBlue Medical Technology. The tests proved to be only 20% accurate and, essentially, worthless. [iv]
Aspen, CO announced it will test every resident for antibodies with kits provided by Aytu BioScience, Englewood, CO. Aytu is a distributor of product made by Zhejiang Orient Gene, Zhejiang, China[v] and was recently issued an FDA warning to relabel their kits.[vi]
A close surgeon friend ordered scores of test kits from Ray Biotech. Although headquartered in Georgia, Ray Biotech also has a large clinical research and sales subsidiary in Guangzhou, China.[vii] Thus far, the test is 25% accurate. He is trying to get his money back, and was told by the company that it had no idea why the tests weren’t working.
Given the problems with Chinese tests, it is not surprising that many of these companies are trying to hide their Chinese connection. Cellex, Inc made headlines on April 1 when it became the first company to receive an EUA approval.[viii] Many news organizations said this was FDA approval, which it was not. On April 8, Cellex told ABC News that the company “is optimistic that 100,000 test kits will be shipped very soon from China to New York City.” While Cellex does have a North Carolina office, all details about its two Chinese locations and a statement regarding its GMP (Good Manufacturing Practices) compliant site in Suzhou had disappeared from its website by April 9.[ix]
Why is the accuracy of certain Chinese tests so low? It may be quality control, the methods of validation, and even mutation of the virus since the initial outbreak.
Since late January, over 5000 Chinese factories have shifted to making medical supplies. Factories which made wood into furniture, are now making masks for hospitals. Sawdust, cockroaches, and foreign material have been found in medical shipments sent to needy hospitals globally. Hospitals seemed incapable of getting samples and strong quality assurances. Recognizing this growing reputation stain, the Chinese government ruled that every health care exporter must first be accredited to sell their products within China. [x] Ironically, the unexpected consequence has been that Chinese affiliated companies such as Cellex, and American companies such as 3M, have had their products held up.[xi]
Another reason for poor accuracy of the antibody kits may lie with the simplified EUA validation requirement. Normally, the FDA requires hundreds of blood samples, IRB (Institutional Review Board) study oversight, and thousands of dollars and hours to approve a test. An EUA, requires only 60 tests subjects. This raises more questions given the novelty of COVID-19: What types of patients were checked to validate the tests? Sicker patients with higher, more easily detectable, antibodies? Healthier or asymptomatic patients with lower, harder to detect, levels? Those who tested negative may not have been negative to begin with, as there are procedural difficulties in obtaining a good specimen. The swab test requires superb knowledge of the nasal anatomy and involves patient discomfort to get an adequate sample. The best option is to use banked blood from before there was an inkling of the pandemic. As we say in research: garbage in, garbage out.
Lastly, this virus has traveled globally and is evolving. Different gene sequences are emerging from various world regions. We don’t know whether tests from China are valid for the strains that we now have in the US.
The lack of reagents and substrates has severely limited our ability to test for COVID-19 active infection and now the same scenario is happening with antibody testing.
Coupled to this perfect storm of rapid FDA authorization, quality control issues, greed, pressure to provide testing, and virus evolution, is the paucity of US made test kits. The lack of reagents and substrates has severely limited our ability to test for COVID-19 active infection and now the same scenario is happening with antibody testing. Despite administration assurances, there is still a severe testing shortage. I know this because of my personal experience in the heavily hit area of Detroit.
As of April 18, at least 72% of the publicly available, pending EUA certifications are from Chinese companies. At most, 11% are from the US. [xii]
Fewer than a dozen US-based companies can make the antibody test. Companies like Henry Schein and Bodysphere are distributing, but not actually making the kits. Bodysphere falsely claimed to have an FDA approved test and had to remove this claim from its packaging and website, while Reuters had to issue a retraction. [xiii]
The antibody test kit is designed very similar to a pregnancy test, except it uses a few drops of blood rather than urine. The (nitrocellulose) sponge, which soaks up the blood, is in limited supply and has hampered some US companies from making test kits. China is not releasing any of these nitrocellulose membranes and the German GE subsidiary, Sartorius, is keeping most of the membrane in Germany. US companies are also being more careful, delaying the release of their test kits while they carry out third party validations, such as OneMilo, Inc (FL) working with Johns Hopkins University (MD), Biomerica (CA) working with Mt Sinai School of Medicine (NY), and Chembio Diagnostics (NY) working with Stony Brook University (NY).
On April 10, on CNN’s New Day, Dr. Anthony Fauci stated, “Within a period of a week or so, we are going to have a rather large number of tests that are available… because other countries have gotten burned by this. They [the tests] really need to be validated. You need to make sure that they’re consistent and that they’re accurate. And that’s what we are doing now both with the NIH and with the FDA, is validating them. As soon as they get validated, they’ll be out there for people to use.” Perhaps he misspoke, but this statement is misleading. Both the NIH and the FDA review submissions, but these two organizations have never themselves validated the results of commercial companies. Within days of this announcement, the NIH announced that the National Cancer Institute (NCI) would be reviewing the accuracy of currently available antibody tests. [xiv] Neither details nor the number to be reviewed have been obtainable despite repeated requests to the NCI by this author.
We may need some 260 million tests just to get started, assuming we need to test our 180 million workers and 80 million students.
Antibody testing is the first step to re-starting our lives, to reuniting us with our families and our jobs. We may need some 260 million tests just to get started, assuming we need to test our 180 million workers and 80 million students. No one company can produce enough of these tests. We need good, quality tests, regardless of the country of origin. Period. But without appropriate and consistent testing, we face a second, or even multiple, waves of reinfection, until a vaccine becomes available.
Here are four simple, straightforward steps to get antibody testing right:
1. Scale back the free-for-all of EUA for antibody testing to include only those companies that can prove third party validation by a reputable, US based institution, such as a university or tertiary care hospital using samples from US patients. Given the number of US infections, this type of validation on 60 patients should only take a matter of days. Accept only tests with at least 95% accuracy.
2. Create a standard of sensitivity so that all tests should be able to detect the same, minimum, concentration of antibodies; otherwise, different companies’ tests will have inconsistent findings with each other.
3. Require all manufacturers and third-party distributors to disclose on the kit and all marketing materials where the kit is made and if any key components originate outside of the US.
4. To the extent possible, assist US based manufacturers to procure the components needed to quickly scale up production of their tests.
Accurate, affordable and available antibody testing is the next great leap to overcoming this pandemic. We have adapted to life inside our homes, but delays, sloppiness, indecision on masks, and continued widespread testing shortages, have prolonged the challenges of social isolation. We should learn and adapt from the mistakes of other countries and smaller US missteps. In the weeks to come, we will face further, tougher questions about privacy, discrimination, and regulation of the test results. For now, we must listen to Darwin: adapt to a concerted, logical, aggressive and accurate approach to antibody testing, so we can quickly evolve to victory.
[i] https://medium.com/@smmalinowski/eight-ways-to-smash-not-just-flatten-the-coronavirus-curve-d7b27167d28f
[ii] https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations#covid19ivd
[iii] https://www.bloomberg.com/news/articles/2020-04-01/faulty-virus-tests-cloud-china-s-european-outreach-over-covid-19, https://dailycaller.com/2020/03/31/list-countries-faulty-coronavirus-supplies-china/ , https://www.newsweek.com/uk-says-millions-coronavirus-test-kits-bought-china-unreliable-most-patients-1496506
[iv] https://www.texastribune.org/2020/04/10/laredo-texas-coronavirus-tests-did-not-work/
[v] https://irdirect.net/prviewer/release/id/4293729
[vi] https://www.aspendailynews.com/news/pitkin-county-looks-to-private-sector-testing-options-no-guarantees/article_fa7dbfd2-6e40-11ea-badd-8f00f2869131.html
[vii] https://www.emorybusiness.com/2016/01/21/rani-huang-bets-big-on-cutting-edge-biotech/
[viii] letter to CEO James X. Li, Ph.D.: https://www.fda.gov/media/136622/download
[ix] https://web.archive.org/web/20200403015403/http://cellex.us/
[x] https://www.scmp.com/news/china/diplomacy/article/3078427/coronavirus-chinas-new-export-restrictions-medical-supplies
[xii] https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2
[xiii] https://www.rttnews.com/3083573/bodysphere-falsely-claimed-fda-s-eua-for-covid-19-testing-kit.aspx
[xiv] https://www.cnn.com/2020/04/14/health/fda-reverses-antibody-tests/index.html
