Challenges and Controversies to Testing for COVID-19

Abstract

The coronavirus disease (COVID)-19 pandemic has placed the clinical laboratory and testing for SARS-CoV-2 front-and-center in the worldwide discussion of how to end the outbreak. Clinical laboratories have responded by developing, validating and implementing a variety of molecular and serologic assays to test for SARS-CoV-2 infection. This has played an essential role in identifying cases, informing isolation decisions and helping to curb the spread of disease. However, as the demand for COVID-19 testing has increased, laboratory professionals have faced a growing list of challenges, uncertainties and, in some situations, controversy, as they have attempted to balance the need for increasing test capacity with maintaining a high-quality laboratory operation. The emergence of this new viral pathogen has raised unique diagnostic questions for which there have not always been straightforward answers. In this commentary, the author addresses several areas of current debate, including 1) the role of molecular assays in defining the duration of isolation/quarantine, 2) whether the PCR cycle threshold value should be included on patient reports, 3) if specimen pooling and testing by research staff represent acceptable solutions to expand screening, and 4) whether testing a large percentage of the population is feasible and represents a viable strategy to end the pandemic.

Comparison and correlation of commercial SARS-CoV-2 real-time-PCR assays, Ireland, June 2020

“…Using C t values to influence patient management is complex and must be done with caution. Including the C t value on positive results may be confusing and misleading [ 12 ]. With no clearly defined infectious dose for SARS-CoV-2, viral culture not available routinely and C t values differing by up to 6.5 cycles between platforms, one would question the value of the routine use of reporting C t values for patient management.…”

“…misleading [12]. With no clearly defined infectious dose for SARS-CoV-2, viral culture not available routinely and C t values differing by up to 6.5 cycles between platforms, one would question the value of the routine use of reporting C t values for patient management.…”

Broad respiratory testing to identify SARS-CoV-2 viral co-circulation and inform diagnostic stewardship in the COVID-19 pandemic

“…Importantly, this study illustrates the challenges in performing direct, year-to-year comparisons of broad surveillance data for respiratory viruses. (16,30,31). As test volumes increase with the upcoming influenza season, diagnostic stewardship is a key strategy to prioritize public health as the pandemic continues.…”

“…Since SARS-CoV-2 emerged, there has been little research on the concurrent circulation of these other respiratory viruses, which had been the subject of broad surveillance in the years prior (2)(3)(4)(5): only a handful of case reports have described coinfections between SARS-CoV-2 and other respiratory viruses able to cause similar symptoms (6)(7)(8)(9)(10)(11)(12)(13). With unprecedented demand on clinical diagnostics, re-prioritized surveillance is one of many ways that laboratories have had to prioritize and adapt throughout this pandemic (14)(15)(16)(17). However, understanding current virus co-circulation could help to develop evidence-based strategies to better tackle the pandemic in future pandemic surges and the approaching influenza season, as exponentially increasing numbers of patients require testing for COVID-19-like symptoms.…”

COVID-19 Vaccination: From Interesting Agent to the Patient

“…In the latter stages, for correct and accurate reading, swabs from the lower respiratory tract will yield a higher rate of detection. Due to these nuances, it has been challenging laboratory professionals to truly define the clinical sensitivity of SARS-CoV-2 real-time PCR and has required that negative results be interpreted in the context of the timing of the sample [24]. An example of problems faced for SAR-CoV-2 RT-PCR testing is shown in Figure 2.…”