Misdiagnosis of SARS-CoV-2: A Critical Review of the Influence of Sampling and Clinical Detection Methods

Abstract

SARS-CoV-2 infection has generated the biggest pandemic since the influenza outbreak of 1918-1919. One clear difference between these pandemics has been the ability to test for the presence of the virus or for evidence of infection. This review examined the performance characteristics of sample types via PCR detection of the virus, of antibody testing, of rapid viral antigen detection kits and computerised tomography (CT) scanning. It was found that combined detection approaches, such as the incorporation of CT scans, may reduce the levels of false negatives obtained by PCR detection in both symptomatic and asymptomatic patients, while sputum and oral throat washing sample types should take precedence over swabbing when available. Rt-PCR assays for detection of the virus remain the gold-standard method for SARS-CoV-2 diagnosis and can be used effectively on pooled samples for widespread screening. The novel Oxford antibody assay was found to have the highest sensitivity and specificity of four currently available commercial antibody kits but should only be used during a specific timeframe post-symptom onset. Further research into transmission modes between symptomatic and asymptomatic patients is needed. Analysis of the performance characteristics of different sampling and detection methods for SARS-CoV-2 showed that timing of sampling and testing methods used can greatly influence the rate of false-positive and false-negative test results, thereby influencing viral spread.

Keywords: COVID-19; Rt-PCR; SARS-CoV-2; antibody tests; antigen tests; asymptomatic; detection methods; diagnosis; sampling; symptomatic.

Figure 1

The time sensitive changes of antibody detectivity levels within COVID-19-positive patients over time when tested using available and marketed commercial kits—Abbott, DiaSorin, Roche and Siemens.

Figure 2

Longitudinal analysis of COVID-19 percentage positivity rates when sampled across 213 hospitals in China, over 15+ days, using nasopharyngeal (NP), oropharyngeal (OP) swabs and sputum samples (adapted from [73]).

Figure 3

The deduced hierarchy in sample type and CT scan efficacy for diagnosis of COVID-19 disease, in both hospitalised patients and outpatient/mobile clinics along with the recommended disease-stage progression time-point to test at.