RE: Rapid Diagnostic Technology and Concerns for SARS-CoV-2 Infections
References
Thwe PM, Ren P. How many are we missing with ID NOW COVID-19 assay using direct nasopharyngeal swabs? Findings from a mid-sized academic hospital clinical microbiology laboratory. Diagn Microbiol Infect Dis 2020 Oct;98(2):115123.
Lephart PR, Bachman MA, LeBar W, et al. Comparative study of four SARS-CoV-2 nucleic acid amplification test platforms demonstrates that ID NOW performance is impaired substantially by patient and specimen type. Diagn Microbiol Infect Dis 2020;99:115200.
Hirotsu Y, Maejima M, Shibusawa M, et al. Comparison of automated SARS-CoV-2 antigen test for COVID-19 infection with quantitative RT-PCR using 313 nasopharyngeal swabs including from 7 serially followed patients. Int J Infect Dis 2020;99:397-402.
Scohy A, Anantharajah A, Bodéus M, et al. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol 2020;129:104455. doi: 10.1016/j.jcv/2020.104455
Ogawa T, Fukumori T, Nishihara Y, et al. Another false-positive problem for a SARS-CoV-2 antigen test in Japan. J Clin Virol 2020;131:104612. doi: 10.1016/j/jcv.2020.104612
The clinical diagnosis of COVID-19 is fraught with difficulty given overlap with many other atypical pneumonia agents and their presentations. Whereas the mainstay of laboratory diagnosis is SARS-CoV-2 RNA detection after genetic amplification, there have been many recent discussions by provincial and federal politicians, and others, of imminent rapid access technologies that would putatively change the epidemiology of COVID-19 if available and implemented. These are considered variations on point-of-care diagnostics. Experience with both coronavirus-specific and other microbe-related diagnostic techniques may prove otherwise.
Rapid nucleic acid amplification may have its limits for a variety of reasons.(1,2) The volition to speed up amplification processes or use other methods than conventional RT-PCR can be associated with considerably reduced sensitivity of the assay. Direct antigen detection for microbial infection has long been studied, but success most often comes when the microbial antigen to be detected is plentiful in a clinical sample, e.g. bacterial capsule. For SARS-CoV-2, more commonly detectable antigens appear to be surface attachment factors such as S protein, but for clinical samples, sufficient antigen for detection may only be present with high viral loads.(3-5) Therefore, again, the sensitivity of the assay will very much depend on the timing of acquisition, and there are likely to be many circumstances where patients are being sampled in low probability situations when these tests are practically applied, e.g., contacts, early pre-symptomatic infection, or late infection. The latter imparts a potentially low sensitivity of these tests when compared to RT-PCR.(3-5) Point-of-care testing is also influenced by factors such as quality of specimen collection, compliance with instructions, ease of interpretation, among other. The latter become more problematic when users of the system are lesser skilled as when tests are being conducted by non-laboratory workers. Such dilemmata are well-known from experience with historic such rapid diagnostics.
Compounding these issues is the projection by some mainstream politicians that a major investment in these technologies could dramatically change the landscape in the current COVID-19 pandemic. These individuals often have the best of intentions with forward-looking plans and the need to console the populace at heart with the promise of positivity in a storm of change. In the scheme of pandemic management, however, it is critical for clinicians and scientists to appropriately guide our public services and governmental policies. Indeed, it should be these individuals that accurately speak on the constructive changes in health and technology rather than the politicians who may feel pressured to do so but with more limited knowledge bases. Validity in the management and diminution of COVID-19 is far more likely to have an impact on success and population health than blinded positivism.