Call in the Biomedical National Guard: Where are the coronavirus tests?
As we read the news about the novel coronavirus and COVID-19, we are constantly left with one question: where are the tests? Why is there no coordinated plan for testing? There is no doubt that any plan for controlling the coronavirus pandemic and returning to normal activities must include adequate and coordinated testing. And now, on June 25, 2020, there are reports that President Trump will end federal funding for testing sites. As cases continue to rise in many states, now is the time to increase, not reduce, access to testing.
As one step to solve this problem, months ago we proposed the creation of a “Biomedical National Guard” that would get thousands of other labs like ours running millions of more tests every week. We have shared this with our university, the entire Michigan congressional delegation, and published an op-ed in The Wall Street Journal; Jack Lipton, our department chair, was on NPR, Bloomberg News, Fox News, and MSNBC. The response…crickets.
Update 6/25/2020 7:00 PM: We learned today that members of the Michigan congressional delegation, in particular, U.S. representatives Elissa Slotkin, Fred Upton, and Senator Debbie Stabenow, were able to influence policy change based on our proposal. We shared our proposal for easing CLIA regulations to facilitate increased testing volume outside of clinical diagnostic labs with a bicameral and bipartisan assembly of the Michigan congressional delegation on April 22nd. Statements were added to the “Testing Blueprint: Opening up America Again” released by the White House, FDA, and CDC release on June 15, 2020. Federal guidance now explicitly supports colleges and universities using academic labs to support surveillance testing of staff, faculty, and students, as well as other outside groups if positives are confirmed by a certified laboratory. This does not provide funding or a long-term plan to create a Biomedical National Guard, but it’s a start.
How much testing do we need?
Analyses estimate that we need anywhere between 600,000 (Harvard Global Health Institute) to 22 million (Nobel Laureate Paul Romer) tests per day. However, U.S. testing capacity for the novel coronavirus is currently only at around 500,000 per day. In the absence of federal guidance and coordination, even the current testing capacity is not being well-utilized. Because of the lack of clear guidelines, states are adopting inconsistent policies leading to confusion and eroding trust. Businesses, schools, and other organizations have been left to make their own decisions about testing and opening without guidance or clear information. Testing remains largely voluntary and patient-driven, but not part of a coordinated program to get us back to work, school, and other activities.
The reality is this: without significantly more labs and trained personnel working in a coordinated testing and tracing program, we will be unable to collect the data we need and the U.S. will continue to lag behind the world in our COVID-19 response — now and in every subsequent recurrence of the virus.
There are a number of explanations for why the U.S. continues to lag behind on testing (explained in detail elsewhere). Tens of thousands of academic labs in the US have the knowledge, expertise, and equipment to run PCR tests for coronavirus. But these labs have been sitting mostly idle since mid-March. If we could mobilize existing infrastructure to tackle this problem, testing capacity in the U.S. could drastically increase nearly overnight. So what’s the hold-up? Where are the COVID tests?
What are PCR-based tests?
One type of test we need is PCR-based tests. For the novel coronavirus causing COVID-19, this involves measuring how much viral RNA is present in a sample.
PCR, or polymerase chain reaction, is a standard lab technique that allows scientists to make many copies of small bits of DNA. This reaction runs in repeating cycles, with each cycle of the reaction doubling the number of copies. The novel coronavirus (SARS-CoV2) is an RNA virus, so scientists use something called reverse transcription (RT) to first create DNA from the RNA sequence. Then, they copy the resulting DNA with PCR in a combined process known as RT-PCR. The resulting amount of DNA present at the end of the reaction can be used to determine how much material was present in the original sample.
qPCR, which stands for quantitative PCR, allows scientists to measure how much DNA is present in real-time, after each cycle of the reaction (instead of only at the end of all cycles), by measuring light emitted by fluorescent dyes that bind to the DNA. The more DNA that is present, the greater the amount of light emitted at each cycle. The PCR tests for the novel coronavirus SARS-CoV2 use a combination of these methods: quantitative reverse transcription PCR.
Back in March, our department (the Department of Translational Neuroscience at the College of Human Medicine of Michigan State University) implemented a test using a modification of qPCR called droplet digital PCR (ddPCR). This uses the same basic principles but provides 500 times greater sensitivity than regular qPCR. This means this method can detect viral RNA at levels 500 times lower than regular qRT-PCR, which should reduce false-negative results in people with low viral loads. Reducing the false-negative rate is especially important given the evidence of presymptomatic and asymptomatic spread. Being able to detect infected people who are not reporting symptoms is critical to containing and understanding the spread of this disease.
Our protocol was developed to not rely on high-demand equipment or products that have been difficult or expensive to obtain. When our COVID team learned that the nasal swabs were expensive and uncomfortable (which may lead to subjects jerking away and yielding less test material, or to subjects choosing to not be tested at all), they adapted the test to use spit. When they found that the spit kits were pricey, they built their own for a few bucks each from equipment that most labs have on hand.
In short, we have developed a cheap and easy protocol that thousands of labs around the country could implement.
Who is capable of running PCR tests?
PCR is a standard technique in labs across disciplines from biomedical fields to plant biology. The untapped testing capacity of these labs is enormous. The required equipment, as well as the expertise needed to run these, is widespread throughout academic labs across the US. There are tens of thousands of academic labs that have the equipment, ability, and personnel needed to perform these tests. There are thousands of ddPCR systems and tens of thousands of qPCR machines in academic labs around the country.
Why can’t academic labs do clinical testing?
Despite the large number of academic labs in the US, most cannot perform any clinical testing because they don’t have the required certification. Only Clinical Laboratory Improvement Amendments (CLIA) certified clinical testing labs are able to perform clinical and diagnostic tests. The CLIA certification system, managed by the Centers for Medicare and Medicaid Services (CMS), does not allow academic labs to run clinical tests without a full application and accreditation — a time-consuming and impractical process for a lab requesting to run a single clinical diagnostic assay. In addition, without CLIA certification, academic labs are not eligible to apply for Emergency Use Authorizations (EUA) from the FDA.
Under normal circumstances, the inability of academic labs to do clinical testing is not a problem because we have adequate testing capacity at CLIA labs for the wide range of clinical tests we need. However, CLIA requirements are preventing labs that are ready and willing from doing a very simple protocol at a time when we desperately need to ramp up testing capacity for one, relatively simple test.
Can a Biomedical National Guard mobilize existing infrastructure to expand testing capacity?
If existing academic labs were able to perform these tests, we could expand testing capacity in the U.S. to a level that could match the estimates for daily testing recommended by public health experts. Combined with clear guidelines for states and institutions and a coordinated test/trace/isolate program, this expanded capacity has the potential to drastically change the course of this pandemic in the US.
We proposed creating a Biomedical National Guard made up of thousands of university-based, high-complexity molecular biology laboratories, each armed with rigorously trained staff and faculty who have spent their careers researching ways to alleviate the pain and suffering of humankind.
These state-of-the-art labs can easily and quickly meet the standards of competency required by the FDA to run authorized SARS-COV-2 viral tests. Their directors and staff work on the cutting edge of scientific knowledge and are arguably the most educated, competent, and well-trained biomedical workforce in the world. Academic labs run in highly regulated environments and are annually certified in biological safety, human and animal bloodborne pathogens, and chemical hygiene. If even one-half of these labs participated in a nationwide rescue mission, testing capacity could exceed 3 million tests per day.
Specifically, CMS could temporarily broaden the definition of “certified laboratories” to include academic labs that demonstrate a validated test for the novel coronavirus in accordance with the standards set forth in current FDA and CMS guidelines. The national need for broadened authorization can be in effect for 90 days and reauthorized and extended as needed by CMS every 60 days until this crisis abates. The parent institution of these newly certified labs would continue their regulatory oversight and set standard processes for intake, handling and tracking of samples, and reporting of results in accordance with CLIA guidelines. Together, these certified laboratories would form a Biomedical National Guard available to be activated when testing demand becomes too high during an outbreak.
By getting America’s academic laboratories involved in the testing process, we can work toward a long-overdue coordinated nationwide strategy of test/trace/isolate and that gets Americans safely back to work and normal activities.
Such measures and creative solutions are long overdue. The slowness to act at every level from our university to the President is a failure to the American people. You should be asking why every business, every school, every organization does not have access to regular testing. You should be asking why scientists have been calling for coordinating testing programs for months but no changes have been made to establish a such a program. You should be asking yourself why, over 3 months into this pandemic, we are still left wondering “Where are the coronavirus tests?”
This article was co-written by Alison Bernstein and Jack Lipton. Alison Bernstein is an Assistant Professor and Jack Lipton is Professor and Department Chair in the Department of Translational Neuroscience at the College of Human Medicine at Michigan State University. Our department has implemented a PCR-based test based on a medRxiv preprint but we are unable to use it for clinical testing. Alison Bernstein is also a Co-Founder of SciMoms (@SciMoms), a non-profit educational organization that aims to promote evidence-based parenting and policy.
This post was updated on June 25, 2020 in light of news reports that President Trump is ending federal funding for coronavirus testing sites.