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.

Microarray-Based Detection of Antibodies against SARS-CoV-2 Proteins, Common Respiratory Viruses and Type I Interferons

“…However, it remains unclear whether the false-positive signals that we observed were the result of cross-reactive interactions with antibodies against other coronaviruses and whether the analysis result was influenced by endogenous factors associated with an autoimmune inflammatory process or by a combination of factors. Antibodies against the nucleocapsid of SARS-CoV-2 are an attractive diagnostic marker, as they appear earlier than antibodies against the spike protein [46]. However, considering possible cross reactions, the ideal choice for the development of an immunoassay is simultaneous assessment of both the nucleocapsid and spike proteins.…”

Ultra-Fast Electrochemical Sensor for Point-of-Care COVID-19 Diagnosis Using Non-Invasive Saliva Sampling

“…Of these samples, typically nasopharyngeal and oropharyngeal swabs are widely used in the diagnosis of early infection [18,19]. However, these sample collection techniques suffer from certain limitations including unpleasant sample collection procedure, especially for children [20,21], shortage of reagents including the viral transport media [12], increased false negative rates [22] due to insufficient sampling of nasal cells and an increased risk of occupational exposure among the clinical staff who collect the samples at the frontlines. The oral throat wash may provide deeper access to the oropharyngeal area.…”

Microarray-based detection of antibodies against SARS-CoV-2 proteins, common respiratory viruses and type I interferons

“…However, it remains unclear whether the false-positive signals that we observed were the result of cross-reactive interactions with antibodies against other coronaviruses and whether the analysis result was influenced by endogenous factors associated with an autoimmune inflammatory process or by a combination of factors. Antibodies against the nucleocapsid of SARS-CoV-2 are an attractive diagnostic marker, as they appear earlier than antibodies against the spike protein [30]. However, considering possible cross reactions, the ideal choice for the development of an immunoassay is simultaneous assessment of both the nucleocapsid and spike proteins.…”