As the world prepares for the approval of COVID-19 vaccines and treatments, many organizations are also beginning to think about the eventual “re-opening” of venues including workplaces and loosening restrictions for events and gatherings. To facilitate this process, COVID-19 testing can better equip organizations to both protect individuals and minimize the spread of disease. The availability of widespread testing capabilities would benefit these organizations, but also address public health and societal needs. Two of the most predominant testing methods—polymerase chain reaction (PCR) and rapid diagnostic tests—could be used to shorten testing cycles and ensure more confidence in results.

  • PCR is the primary method for diagnosing COVID-19 due to its perceived higher sensitivity and specificity, meaning its ability to accurately diagnose positive and negative cases, respectively. However, PCR testing faces challenges at the scale required to test across the United States and parts of western Europe. PCR takes a long time to produce results, with an average U.S. turnaround time of more than four days, and up to ten or more days in certain parts of the country (figure 1). Some of the reasons for the slow turnaround time include supply shortages including sample collection swabs, virus transport media and test reagents, and laboratory limitations like number of testers and testing apparatuses.
  • Rapid diagnostic tests collect samples at the point of care and provide test results in as little as 15 minutes (figure 1). With increased use, rapid diagnostic tests potentially could shorten the COVID-19 testing cycle. Rapid molecular tests such as Abbott’s ID NOW and antigen tests such as Quidel’s Sofia SARS Antigen FIA currently are available, but their use is limited to healthcare professionals with access to the necessary testing base unit. Lateral flow tests such as Abbott’s BinaxNOW could enable a 15-minute turnaround for results without the need for a base unit. Partly due to this higher usability, the U.S. government has secured a $760-million deal with Abbott to deliver 150 million BinaxNOW tests. Initial shipments of these tests arrived in Georgia and other states in early October.
Although rapid COVID-19 tests could alleviate some of the bottlenecks in the PCR testing process, most of the clinical data on the accuracy of these rapid tests has been demonstrated in symptomatic populations. As further data is generated, the use of widespread, highly-specific rapid testing can be a valuable tool for more effective triaging of individuals who require a PCR test to validate their positive result and allowing individuals who test negative to return to activities like school and work. This use case can allow for the expedited reopening of businesses as negative cases are identified, and the burden on PCR tests is reduced through limiting PCR use to confirming positive cases detected via more readily accessible rapid tests. For these reasons, we propose two layers of testing: widespread, highly-specific rapid tests that act as an initial filter, and PCR tests to confirm positive cases.

The PCR testing value chain—including sample collection, transportation logistics and test administration—contains several constraints that can contribute to delayed test results. These delays can exacerbate the virus transmission cycle while an individual awaits results for two reasons:

  • An individual who is positive for COVID-19 is unaware of her status and at risk of unknowingly spreading the virus
  • An individual who is negative for COVID-19 may unnecessarily self-quarantine while she awaits results, thus slowing her return to certain social activities such as school and work

Tests with quicker turnaround times will both reduce the duration of or eliminate self-quarantining and, accordingly, reduce disease transmission from infected individuals to those they come into contact with. To demonstrate how and why highly-specific rapid tests may be of equal or greater importance than highly sensitive tests, we must first define and differentiate test sensitivity and specificity. The current focus of COVID-19 testing efficacy has primarily been on sensitivity, or what proportion of positive cases will be properly detected by the test. On the other hand, specificity refers to the ability to correctly identify a negative result for individuals who don’t have the virus. Thus, highly-specific rapid tests could enable better identification of negatives to gradually begin returning to the social activities that have been subject to social distancing restrictions. For example, companies looking to re-open their physical buildings could use rapid tests to identify negative individuals who can more safely return to the office.

 

Specificity and sensitivity are important metrics for test accuracy, however, the context of local disease incidence can impact the relative predictive value of test results. Rather than assuming these measures are absolute, they’re best viewed through the lens of relative predictive power, either for a confirmed positive or negative diagnosis. We looked at test outcomes in two hypothetical towns, each with a population of 10,000 people. Town 1 has a lower prevalence of COVID-19 (at or below a 1.6% expected positivity rate) and Town 2 has a higher prevalence of COVID-19 (about 10%). Each town uses a rapid test with sensitivity of 97% and specificity of 99%. 

What we found: In Town 1, five people infected with COVID-19 would receive a false negative test result, whereas 30 COVID-19-infected people in Town 2 would receive a false negative result. In Town 1, 305 individuals who test positive would undergo PCR testing to confirm their positive status, whereas 1,110 individuals in Town 2 would undergo PCR testing to confirm their status.

 

Assuming that highly-specific rapid tests are available, 9,695 individuals in Town 1 could return to work and daily life with higher confidence than in Town 2 due to the lower number of COVID-19 positive individuals who test negative. In Town 2, rapid tests are relatively less useful due to a higher number of infected individuals that would test negative, and a higher number of positive tests that can be confirmed with PCR to determine the infection status of the individual.

 

To understand these implications, we’ll examine real-world examples in New York and Florida, where there’s been a low and high prevalence of COVID-19, respectively. 

What we found: In New York, 65 COVID-19-infected people would receive a negative test result, whereas in Florida, 560 COVID-19 infected people would receive a negative result (per 100,000 people). In New York, 2,025 individuals who test positive can undergo PCR testing to confirm their positive status, whereas in Florida, 11,350 individuals can undergo PCR testing to confirm their status.

 

Using highly-specific rapid tests, 97,910 out of each 100,000 individuals in New York could return to work and daily life, and only 2,025 out of each 100,000 individuals would need to undergo PCR testing to confirm a positive test result. On the other hand, in Florida the use of highly specific rapid tests would face greater challenges: 560 people infected with COVID-19 would receive a negative test result and the 11,350 individuals would still need to undergo confirmatory PCR testing (out of each 100,000 tested). Therefore, PCR would likely continue to be the preferred testing method in Florida.

 

Generalizing the conclusions from these two examples, areas like New York that have lower prevalence could leverage two layers of testing (first with rapid testing to determine true negatives and then with PCR testing to confirm positive rapid test results) to conserve PCR resources, prevent new infections and return people to work and daily life. PCR resources in lower prevalence areas could then be redeployed to areas with higher prevalence, like Florida. These areas either need to continue using PCR for all tests or limit community spread before using rapid testing due to the higher number of infected individuals who test negative and the higher number of positive tests that would need to be retested with PCR. This would enable people to return to certain social activities sooner, reduce transmission risk as rapid testing is expanded and executed at greater scale with less testing delay, and preserve PCR resources where they are constrained today.