The U.S. effort to deploy diagnostics for the novel coronavirus has been plagued by missteps by the CDC and the FDA from the outset, leading to delays and missed opportunities. The Trump administration declared a national emergency March 13, but concerns remain about how quickly the array of available tests can be conducted and whether there are enough testing supplies to handle the anticipated demand.

The complexity of the lab testing procedure for this pathogen is hinted at by a guidance provided by the CDC. This guidance is directed toward the use of real-time, reverse transcription polymerase chain reaction (RT-PCR) testing, which requires the use of three assays. One of the assays is directed toward universal detection of SARS-like coronaviruses while the other two are for specific detection of SARS-Cov-2. The document provides specifications for supplies, equipment and nucleic acid extraction procedures. FDA commissioner Stephen Hahn has indicated that the emphasis was to avoid false negative returns in an effort to blunt any preventable local transmission, a strategy he indicated was based on sound science.

However, the CDC test performed unevenly in the field, rendering inconclusive results for the wider coronavirus component, even though the results were consistent for the two assays specific to SARS-CoV-2. That led CDC officials to question the reliability of the test, which has reportedly been driven in part by contamination. CDC officials have neither corroborated nor denied that explanation. CDC director Robert Redfield acknowledged in a Jan. 31 press briefing that the test developed by the agency had proven unreliable, providing alternate outcomes for a given patient over a span of days.

The World Health Organization (WHO), which recently declared the COVID-19 outbreak a pandemic, has recommended the use of polymerase chain reaction (PCR) testing, with screening protocols “adapted to the local situation.” WHO recommended that affected nations deploy tests relying on nucleic acid amplification via PCR technology. One of the alternatives to PCR is the technology underlying the rapid influenza diagnostic test, which is designed to detect surface proteins, or antigens. This approach provides far less sensitivity than PCR testing, however, although it is widely available at the point of care in many nations. This method, while more quickly deployable, is associated with a large percentage of false negatives, the outcome both the CDC and the FDA seek to avoid.

In the instance of South Korea, scientists at Seegene Inc., of Seoul had obtained regulatory approval for their test from South Korean authorities in a mere week in mid-February. The Allplex 2019-nCoV assay is a single-tube assay developed with the help of artificial intelligence for use with the company’s proprietary reader. However, South Korean officials are also able to track citizens who have been diagnosed via credit card transactions and GPS tracking from cell phones. The statute in South Korea also allows the government to make such information publicly available as well, a set of measures that would be unlikely to find welcome in the U.S.

Two emergency declarations, narrow EUA

The U.S. Department of Health and Human Services has responsibility for announcing public health emergencies, the first of which was announced Jan. 31. In this instance, the emergency was authorized under Section 319 of the Public Health Services Act, which is in force for 90 days and covers disease outbreaks. However, the FDA said Section 319 does not allow the agency to issue emergency use authorizations (EUAs) for diagnostics, stating that an emergency declaration under Section 564 of the PHS is necessary. HHS declared a Section 564 emergency several days later in a Federal Register entry of Feb. 4, which was followed by an FDA announcement of an emergency use authorization (EUA) for the CDC test.

However, the initial version of the FDA’s EUA required that the CDC test be run twice on a given patient, and would not allow any tests other than the CDC test to be conducted even though public labs had already forged ahead with their own validated tests. On Feb. 29, the FDA finally relented, allowing labs to run internally validated tests with a 15-day deadline to notify the FDA of the test, but precious time had already been lost.

Private sector joins the fray

The Trump administration announced that private test makers have agreed to roll out their own tests, and the FDA has announced several expansions of the EUA to permit testing with these systems. Among the companies making tests for the SARS-CoV-2 virus is Thermo Fisher Scientific Inc., of Waltham, Mass., which said its test runs in four hours, a time frame that does not include the time needed to ship the samples to the lab, or the time needed to collect the samples from patients. This test is available for the company’s Applied Biosystems 7500 real-time polymerase chain reaction (PCR) platform. Labcorp of Burlington, N.C., is also providing tests at labs that can run their assays, as is Quest Diagnostics Inc., of Secaucus, N.J.

There are issues associated with the availability of supplies used in testing in the U.S. CDC’s Redfield has indicated that the supply of reagents may be crimped, halting the diagnostic process at the point of RNA extraction. Deborah Birx, who serves as the response coordinator for the federal government’s coronavirus task force, has also indicated that labs should take measures to ensure they have sufficient supplies of items such as pipette tips.

Qiagen Inc. of Germantown, Md., which was recently acquired by Thermo Fisher, has indicated that reagent production could be a bottleneck in tests distributed to labs by that company, a problem FDA commissioner Stephen Hahn confirmed in his March 11 testimony before a House committee. Hahn also indicated that the variety of testing platforms and test types in use in the U.S. further complicated the effort to roll out a test that could be deployed in all locations across the U.S.

Masks, ventilators also in short supply

One of the relatively less conspicuous elements in the COVID-19 outbreak is the need for personal protective equipment (PPE) and hospital equipment, such as N95 respirator masks and ventilators. Sen. Ed Markey (D-Mass.) penned a March 15 letter to President Trump urging the use of authorities described in the Defense Production Act to ramp up manufacture of personal protective equipment. Markey said the Strategic National Stockpile (SNS) has 12 million N95 masks on hand, but that the need may ultimately exceed 3.5 billion units, an estimate provided by assistant HHS Secretary Robert Kadlec in his March 3 testimony to the Senate Health, Education, Labor and Pensions Committee.

Among the bills in play that would address at least some aspects of the PPE dilemma is H.R. 6201, the Families First Coronavirus Response Act. This legislation would provide free coronavirus testing and would exempt PPE from certain legal liabilities. A Senate bill, the Health Care Workforce Protection Act of 2020 (S. 3372), likewise takes up the liability question, although this bipartisan bill has been locked up by opposition from Senate Democrats. The FDA has advised health care professionals that PPE may in some circumstances be used outside the normal recommendations for disposal.

The picture for hospital ventilators is likewise a source of concern, given the effect of the virus on the respiratory system. A Feb. 14, 2020, bulletin by the Johns Hopkins Bloomberg School of Health says that U.S. hospitals carry roughly 62,000 full-featured ventilators, and that another 98,000 limited-function units are also available. That inventory could be quickly overwhelmed in the event of a severe pandemic, the report says, despite the availability of nearly 9,000 additional units in the SNS.

CDC, White House on gatherings

The availability of diagnostics notwithstanding, the U.S. federal government is taking further action to blunt the spread of the virus. The CDC said on March 15 that gatherings of more than 50 people would be ill-advised, a recommendation that applies for the eight weeks following the date of the announcement. This does not apply to those charged with day-to-day operations at a variety of settings, such as schools, universities and businesses.

However, President Trump said in a March 16 press briefing that this recommendation has been elevated to gatherings limited to 10 people for the following 15 days. This initiative has been dubbed, “15 Days to Slow the Spread.”

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