No Lab Has a Closet Full of Tests For a Yet-to-be-discovered Infectious Agent
by: Dr. Monica de Baca
By now anyone with an internet connection knows that there is a new virus on the block and that we’re in the midst of a pandemic. As little as 4 months ago, no one knew of COVID-19. If the statement “No lab has a closet full of tests for a yet-to-be-discovered infectious agent” may have sounded obvious last October, these days it seems to be less obvious.
Let’s keep the timeline in perspective:
• December 31, 2019: China alerted the World Health Organization (WHO) to a cluster of patients with pneumonia of unknown cause. At that time, the virus itself was unknown.
• January 5th, 2020: China had ruled out a recurrence of SARS (severe acute respiratory syndrome virus) and by
• January 7, 2020: had identified a new virus named 2019-nCoV. As the CoV in the name suggests, this was identified as belonging to the coronavirus family of viruses. Initial diagnosis was based on genome sequencing.
• By Jan 21, 2020, several PCR assays had been developed (for example, at U. Hong Kong, China CDC).
• February 4, 2020: the US Secretary of Health and Human Services (HHS) determined that a public health emergency exists and that circumstances justify the authorization of emergency use of in vitro diagnostics for detection and/or diagnosis of the novel coronavirus (2019-nCoV). See HHS website for COVID-19 news.
• February 29, 2020: the FDA released a Policy for Diagnostic Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization for Coronavirus Diseases-2019 during the Public Health Emergency.
When new diagnostic laboratory tests are developed in the “routine” setting, the process is long complex, detailed, while being scrupulously regulated and scrutinized. Clinical laboratory testing is highly regulated to ensure that tests are rationally designed, are performed as designed, that results have a meaning that is understood, are shared between labs and among providers and to generally safeguard the population being tested.
In the pre-pandemic world, developing news tests required significant review of the literature, determination of the necessity for FDA approval/clearance, evaluation of CLIA complexity status, selection of test methods, specimen types, quality and validation studies (validation studies include ascertainment of accuracy, precision, analytical specificity and sensitivity, identification of a reportable range, reference range and detection limit, establishment of interferences or co-reactions, etc.). In the case of an infectious disease, labs must have positive samples to test— until there is an isolated infectious agent that is being tested, no assay can “test positive” for that agent. Similarly, if the number of positive cases is limited, it is essentially impossible for a laboratory to have access to the body fluids, blood or tissues from which the infectious agent could be isolated.
Diagnosing an infectious disease also requires understanding the way that illness is contracted and how the body reacts to the initial infections: what is the time period between contact and the development of symptoms? At what point in this timeframe does a diagnostic test become positive? Is the presence of the infectious agent by a sensitive test always equivalent to disease? Is the newly ill patient contagious at the same time as the symptoms develop? Or even before?
With the newly released policy, the FDA is permitting a relative loosening of some of the usual methodology and regulatory restrictions routinely employed in new test design once an emergency has been recognized; it cuts through red-tape and green-lights the speedier development of novel testing.
Orchestrating the development of a new test for a new pathogen from within a newly emerging epidemic is about as hard as it gets. Yes, there are supply chain issues. Yes, there are issues of public health deployments. Yes, there are issues with national coordination. No, we haven’t figured out isolation and adequate detection. And how to get the economy back on track. And we are heartbroken about the people lost to the disease. And. And. And…… And hundreds of thousands of tests have been run for Covid-19 in the last months. For just one minute, let’s recognize the scientific and medical community for the amazing accomplishment this represents. This is not a lunar landing, this is a significantly greater achievement. Take a picture: that’s us, sitting on a new star, just 4 months after it was discovered.
When there’s a vaccine - someone may even throw us a party.