The United States’ recent increase in testing capacity due to an influx of rapid diagnostics tests (RDTs) has lent itself to a false sense of security with regards to clinical testing during the COVID-19 pandemic. Though even more testing is necessary to contain the spread of the novel coronavirus, the quantity of tests is inconsequential without veritable data on the tests' sensitivity and specificity. As referenced in a previous blog post, the federal government understandably has had to loosen regulations in order to catch up with the staggering rate of transmission.
Regulations for the approval of diagnostics tests are typically subject to strict scrutiny by the federal government and include comprehensive clinical studies to determine their accuracy. However, clinical studies are time-intensive, and time is seemingly the resource that we have the least of (cue ventilators, and doctors). As such, the FDA has weakened specific regulations relating to the development of diagnostic testing for SARS-CoV-2 and invoked an emergency use authorization (EUA) for tests developed by private laboratories and commercial manufacturers. As a condition of provisional approval, test developers must submit an EUA application complete with information regarding both false positives and false negatives. Though this information should be publicly available through an online database, no information regarding sensitivity and specificity has been widely distributed by the FDA for COVID-19 diagnostic tests that have been used in actual clinical settings.
Though the accuracy of available diagnostic tests for SARS-CoV-2 is unclear, we do know one thing for certain: high false-negative rates from molecular tests such as RT-PCR swabs will be catastrophic. An article included in the journal pre-proof for the Mayo Clinic Proceedings aptly elucidated the threat of false negatives with a hypothetical scenario in which every resident of California was given the same SARS-CoV-2 diagnostic test with a 90% sensitivity.
It has been estimated that the COVID-19 rate in California may exceed 50% by mid-May 2020. With a population of 40 million people, 2 million false-negative results would be expected with comprehensive testing. Even if only 1% of the population was tested, 20,000 false-negative results would be expected.
We should bear in mind that depending on the pretest probability of a positive result, a negative result does not preclude a patient from receiving care. “As we rise to this occasion, we would do well to remember the principles of evidence-based diagnostic interpretation lest we augment the very tide we are attempting to stem.” More on this in a future article.
Just as false negatives from molecular tests pose a substantial threat to our nation’s ability to control the spread of the novel coronavirus, false positives from serological tests also present us with significant risk. Should an individual without any known immunity receive a false positive from an antibody-detecting test, they could incorrectly be cleared to return to work. In this case, the individual would be susceptible to contracting the disease. Additionally, a false positive could also result in a weakened adherence to social-distancing and shelter-in-place guidelines, potentially endangering the lives of family, friends, and the community.
Furthermore, the presence of antibodies does not provide answers to two incredibly important questions:
1) Titers of antibodies must be present to indicate immunity;
2) How long such immunity would last. It is important to note that immunity to SARS-CoV-2 has not been scientifically confirmed
As stated by the World Health Organization,
There has been discussion about whether RDTs detecting antibodies could predict whether an individual was immune to reinfection with the COVID-19 virus. There is no evidence to date to support this.
It is clear that the United States does need more SARS-CoV-2 diagnostic tests and it is imperative that those tests be vetted.
To view our list of FDA authorized tests visit the Medherd COVID-19 test database here.