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The COVID-19 test mess: Why RT-PCR testing is not the gold standard when it comes to COVID-19 test screenings

10 Dec 2020

Overview

COVID-19 has upended many long standing conventions. Before COVID-19, droplets were assumed to be primarily responsible for transmission, transmission was assumed to occur at or after symptom onset and children were the most feared vulnerable group for respiratory virus fatalities. Each of these assumptions has been proven inaccurate in the context of COVID-19. It is now widely accepted that aerosols drive COVID-19 transmission, symptom onset is not equal to how infectious an individual is and children are, empirically, least affected by severe clinical COVID-19 outcomes. More recently, COVID-19 challenges yet another assumption: RT PCR tests as the gold standard diagnostic. At the same time, rapid (antigen) testing has been frequently dismissed due to less test accuracy when compared to RT PCR tests. 

While the Dec 3rd US CDC testing guidance continues to hedge on the issue of COVID-19 testing, compelling evidence indicates the 'best' test when it comes to COVID-19, is not the most accurate test. Instead, it's the test that provides a constant COVID-19 test feedback loop for an individual to navigate daily COVID-19 risk transmission to others. Such a feedback loop requires testing on a regular basis (1-3x/weekly), and where results are delivered back ideally less than a few hours, and no more than 24 hours. It enables testing information to be more actionable in a real world context- allowing for more accurate COVID-19 risk navigation in daily life in communities where the infection spread is uncontrolled.

To date, much of the attention has gone to proving the value of rapid testing. But, an equally important factor is reassessing the role of RT PCR testing in COVID-19 asymptomatic/ presymptomatic screenings such as those described in the CDC's recent test guidance for high risk populations. We map out two weaknesses of RT PCR testing in the context of COVID-19 infection control, suggesting conventional thinking is, once again, leading us down the wrong road in fighting COVID-19. 
Problem 1. PCR testing in the US optimizes the individual, not communities 

In the US, and in many countries where testing is still not widely accessible, COVID-19 testing is reserved for those who have been exposed or are experiencing
symptoms. But, with very limited contact tracing in these same areas with testing shortages, many individuals remain unaware of their exposure incidents. This leaves symptom onset as the major precipitating factor to seeking out COVID-19 RT-PCR testing. 

Why does this actually matter? While transmission can occur throughout the incubation period (from time of exposure to symptom onset), the likelihood of it occurring within 3 days prior to symptom onset is high. In other words, by the time an individual gets tested, a critical infectious window, when the likelihood of transmission is high, has already passed.

In settings where RT PCR testing is being used as a regular screening tool (e.g., well resourced businesses and schools), the timing of RT PCR tests often fail to adequately reduce risk in the pre-symptomatic infectious window. Even where RT PCR testing timelines are adequate, the timing is designed to usually optimize protection to a one set of contacts (e.g., school-based, co-workers). This may or may not optimize protection to other contacts in one's COVID-19 bubble, such as family and friends. In this sense, RT PCR tests for screening purposes come with multiple caveats. By in large, most of these caveats are not being communicated to those who are being screened. 

In contrast, high frequency antigen (rapid) testing applied as asymptomatic screening has repeatedly proven effective in breaking transmission chains among high risk communities such as nursing homes and college campuses (See here for evidence). The major takeaway from the growing body of evidence on high frequency rapid testing is that frequency- even with less accuracy- is the valuable commodity to break COVID-19 transmission chains. This contradicts conventional thinking, which largely associates accuracy with a gold standard for a diagnostic test strategy. 
Problem 2. There is a "false positive" problem with RT PCR tests, where positive is associated with infectiousness

  Positive PCR Test = You have the infection (& may or may not be infectious)
                                                              vs. 
                          Positive Rapid Test = You are infectious now

Why? The higher test sensitivity/ specificity means that RT PCR tests will remain positive well past time of a COVID-19 infectious window. And while more information can be obtained via the cycle threshold (Ct level) from RT PCR tests, how much these metrics are disclosed to those tested, much less explained, is questionable.

Why does this actually matter? An artificially long positivity period vs infectiousness period means economically vulnerable communities are penalized for altruistic behavior towards the community. In practice, it creates a disincentive to get tested.
Moving Forward with Mass COVID-19 Test Screening

Perceptions of less accurate testing continue plague discussions around rapid testing. In reality, this is not a question of strength of the evidence of misinterpretation of the evidence but rather perspective. High frequency rapid testing has demonstrated the ability to efficiently idenify COVID-19 positive individuals – while they are infectious—and in turn, disrupt community transmission chains. But, it only works when testing protocols are frequent enough (e.g., aligned with COVID-19 infectious timeline) to establish and maintain a consistent COVID-19 test feedback loop. It's only with this consistent feedback loop that rapid testing can act as an early warning system for more accurate risk navigation.  

While multiple industries have championed the use of rapid testing as a strategy for reopening, there is little incentive to ensure rapid testing is set up with the explicit purpose of breaking transmission chains. Instead, rapid testing has often been primarily used to offer reassure to customers as a one off testing event, where less attention payed to testing timelines and creating early warning systems. 

A year into the pandemic and on the heels of vaccine development, there is still an overwhelming need to downshift into emergency response testing mode. We've lost a lot of time in this pandemic -- public messaging based on access to test resources instead of the actual evidence and muddled scientific debates via social media that constantly cross the lines between areas of expertise and advocacy. It's time to get on the same page because the world is on a very clear track: living alongside COVID-19 for some time to come. 

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