On January 19, 2020, a 35-year-old man with a 4-day history of cough, subjective fever, and recent travel history to Wuhan, China, presented to an urgent care clinic in Snohomish County, Washington. A health alert from the United States Centers for Disease Control and Prevention (CDC) regarding a novel coronavirus outbreak in China1 – in conjunction with his symptoms and travel history – prompted him to seek care. On January 20, 2020, the CDC confirmed that samples from the patient’s nasopharyngeal and oropharyngeal swabs tested positive for that virus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), making this man the first confirmed case of the coronavirus disease of 2019 (COVID-19) in the United States.2,3
Close to 3 months later, >1 million individuals in the United States have tested positive for SARS-CoV-2.5 This rapid spread has been attributed to a number of factors including the high transmissibility of the virus,6,7 especially among asymptomatic or minimally symptomatic carriers;8,9 the apparent absence of any cross-protective immunity from related viral infections; and a delayed public health response.10,11,12
The overall confirmed case number, however, is primarily a function of the scope of testing, which is dependent on the case definition for COVID-19 and the number of tests available. Both factors have proved to be a point of contention as the virus continues its spread throughout the United States, and as a review published in Annals of Internal Medicine pointed out, there is a critical need for ample, accurate diagnostic testing in the face of this historic pandemic.13
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Why Testing Matters
Until an effective vaccine or treatment is available, mitigating the spread of a virus as infectious as SARS-CoV-2 requires taking steps to minimize transmission. The review authors noted that these considerations necessitate reducing the number of people exposed to the virus as well as reducing the basic reproductive number (R0) of the virus. This is most effectively accomplished by employing high rates of testing for infection. In the United States, community transmission began to occur before adequate testing measures were implemented. As such, Americans were forced to follow a population-based mitigation strategy for COVID-19 via measures such as social distancing and stay-at-home orders. A robust testing strategy, however, will support the United States’ to transition to the case-based mitigation strategy seen in a number of other countries. This strategy would allow for:
- Detecting infected individuals.
- Interrupting transmission through isolation of contagious individuals.
- Contact tracing of infected individuals to further mitigate transmission.
In the clinical setting, testing also aids in triage, allocation of personal protective equipment, prevention of nosocomial infections and, once available, decisions regarding treatment. This strategy, however, is contingent on the types of tests available, the resources required for testing, and turnaround time to results.
Early Concerns
The review authors highlight that testing strategies have varied from country to country and are contingent on both the public health resources available as well as the degree of viral spread within respective communities.
Early in the course of the outbreak, the only approved test for SARS-CoV-2 was the CDC assay developed under [EUA] from [FDA], which required samples to be sent directly to the CDC lab in Atlanta, Georgia.
In the United States, testing was arguably slow to ramp up, a fact that has been attributed to a narrow testing indication, limited testing capacity, and regulatory hurdles for developing and conducting tests.13,14,15 Early in the course of the outbreak, the only approved test for SARS-CoV-2 was the CDC assay developed under Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA), which required samples to be sent directly to the CDC lab in Atlanta, Georgia. Kits developed by the CDC were eventually sent to state and local public health laboratories to improve access and mitigate spread, but shortly thereafter, the CDC reported several labs had difficulties in validating results due to a faulty reagent.16,17 As such, guidance to send samples directly to CDC remained, and concerns regarding scope and turnaround time for confirming diagnoses persisted.
After delays in re-issuing validated CDC test kits, the FDA sought to improve access to testing by announcing on February 29, 2020 that they would allow laboratories certified to perform high-complexity testing to “develop and begin to use validated COVID-19 diagnostics before the FDA [had] completed review of their [EUA] requests.” 18 By March 21, EUAs had been granted to >20 diagnostic tests and the number of samples tested per day increased from 32 to >44000.14 The FDA has continued to update their approval process; as of April 30, EUAs have been granted to >50 tests for SARS-CoV-2,19 testing capacity has increased to >230,000 per day,14 with >1 million Americans testing positive.4,5
Improving the Testing Paradigm
Although real-time reverse transcriptase polymerase chain reaction (RT-PCR) based assays of respiratory specimens have been the predominant mode of diagnostic testing in the United States, a number of novel and complementary diagnostic strategies are also being considered. RT-PCR can be resource-intensive and slow; delays also put the contacts of patients under investigation at risk for infection. As the review authors noted, innovative testing strategies such as point of care testing, serologic testing, and home specimen collection, may help expedite both the collection and testing of specimen.
Point of Care Test
A low-complexity, rapid molecular diagnostic test that can be conducted at the point of care, thus not requiring a complex lab or specially trained personnel, will be an important tool for mitigating the spread of COVID-19. On March 21, 2020, the FDA granted its first EUA to the Xpert Xpress SARS-CoV-2 point-of-care test developed by Cepheid, which claims to provide results 45 min.20
“Having a test that will tell you the disease you have, but in 5 days will not help with decisions about triage and where you are going to put patients. We need an answer quickly, ideally we need an answer right away, but any answer that is in less than an hour is something that can be actionable,” noted David Alland, MD, MSc, whose team has been working with Cephied to validate their rapid point of care test.
Having a test that will tell you the disease you have, but in 5 days will not help with decisions about triage and where you are going to put patients.
David Alland, MD, MSc
Chief of Infectious Disease
Rutgers New Jersey Medical School
Dr Alland, professor of medicine, chief of infectious disease, and the director of the Center for Emerging Pathogens and the Rutgers Regional Biocontainment Laboratories at Rutgers New Jersey Medical School, has been a pioneer in the diagnosis, treatment, and molecular study of mycobacterium tuberculosis. He noted that “this is the same problem we had with drug resistant tuberculosis [TB] 10, 20 years before. We were cohorting patients, taking people who were coming into the hospital to get better and making them worse because they were infected with a drug resistant form of TB.”
In the setting of COVID-19, Dr Alland believes a similar concern exists. Patients not infected with SARS-CoV-2 requiring admission to a hospital may, inadvertently, fall ill and possibly die as a result of COVID-19.
The FDA has since granted EUAs to 3 additional point of care tests for rapid detection of SARS-CoV-2.19 Although point-of-care tests are not meant to replace traditional RT-PCR tests conducted in high throughput laboratories, they will likely play an important role in critical decision making for patients. Moreover, they can help minimize the number of healthcare workers being exposed to the virus and potentially falling ill. “In the immediate time frame, a point of care test is not going to help ‘flatten the curve.’ It is going to help keep patients and healthcare workers alive,” said Dr Alland. “In the longer term, a point of care test that can go out and detect cases in the community can help ‘flatten the curve’ and help keep it flat.”
What can clinicians in the US accomplish with point of care testing? Listen to the Weekly Rounds’ discussion, with further insight from David Alland, MD, MSc, Professor of Medicine and the Chief of Infectious Disease at Rutgers New Jersey Medical School.
Also available on, Apple Podcasts, Google Podcasts, Spotify, or wherever you listen to podcasts.
This article originally appeared on Infectious Disease Advisor
