A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis

Otsuka, Yuki; Hagiya, Hideharu; Nakano, Yasuhiro; Omura, Daisuke; Hasegawa, Kou; Yamada, Hidetada; Iio, Koji; Honda, Takeshi; Otsuka, Fumio

doi:10.1016/j.jiac.2021.05.001

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…Variants pose a challenge in controlling this pandemic [125]. Mutations in the viral spike glycoprotein increase the ability to bind to ACE-2 receptors leading to increased disease transmission and severity.…”

Section: Variantsmentioning

confidence: 99%

Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

et al. 2021

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Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

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Section: Variantsmentioning

confidence: 99%

Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

et al. 2021

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“…A HCoV NL63 infection was, a posteriori, diagnosed, based on the result of FilmArray RP2.1, which was furthermore negative for SARS-CoV-2. The authors ultimately ruled out the cross-reaction theory and concluded that this case was false positive by instrument or human error, possibly due to sample contamination [ 31 ]. In our second case (no.…”

Section: Discussionmentioning

confidence: 99%

Comparative Performance Evaluation of FilmArray BioFire RP2.1 and MAScIR 2.0 Assays for SARS-CoV-2 Detection

Tazi¹,

Kabbaj²,

Zirar³

et al. 2022

Advances in Virology

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Background. RT-PCR is the gold standard for COVID-19 diagnosis, but the lack of standardization of assays, whose diagnostic performance may widely vary, complicates the interpretation of the discrepancies that may be encountered. Study design. We conducted a retrospective study over a ten-month period at the Central Laboratory of Virology of Ibn Sina University Hospital of Rabat. We included nasopharyngeal swabs, positive and negative for SARS-CoV-2 on FilmArray BioFire® Respiratory Panel 2.1 Plus, which were subjected to our laboratory’s reference test, MAScIR SARS-CoV-2 M kit 2.0, initially or after a freeze-thaw cycle. The results were compared, and each discrepant sample with sufficient volume underwent the third test, using ARGENE® SARS-CoV-2 R-GENE kit. Results. Of 80 SARS-CoV-2 negative samples on FilmArray, there were no discordant results, whereas of 80 SARS-CoV-2 positive samples on FilmArray, 21 had discordant results on MAScIR, and only 11 could be tested on ARGENE, revealing positive results in 6 cases. 12.7% and 76.5% correspond to the discordance rates for MAScIR (with one or both targets detected on FilmArray), while 14.3% and 100% correspond to those of ARGENE. As the estimated sensitivity and specificity of FilmArray, compared with MAScIR, were 100% and 79.2%, respectively, its lower limit of detection, and ARGENE assay results, made it difficult to distinguish between false positives on FilmArray and false negatives on MAScIR without further investigations. Conclusion. The implementation of a new assay in our laboratory revealed discrepancies suggesting a lack of sensitivity of our laboratory’s reference test, leading us consequently to retain the SARS-CoV-2 positive result of these discordant samples on FilmArray, regardless of the detection of one or both targets. Our study, which is, to our knowledge, the first comparing FilmArray RP2.1 and MAScIR 2.0 assays for SARS-CoV-2 detection, highlights the urgent need to standardize RT-PCR assays for COVID-19 diagnosis.

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“…The concerns regarding the indication and interpretation of SARS-CoV-2 PCR tests raised by Otsuka et al [1] seem to be truly significant. However, we had to notice that they initially used tests targeting the N gene, which is known to be fairly specific.…”

Section: To the Editormentioning

confidence: 99%

Does the E gene provide additional information in SARS-CoV-2 PCR?

Zóka¹,

Bekő²

2021

Journal of Infection and Chemotherapy

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A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis

Cited by 3 publications

References 6 publications

Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Comparative Performance Evaluation of FilmArray BioFire RP2.1 and MAScIR 2.0 Assays for SARS-CoV-2 Detection

Does the E gene provide additional information in SARS-CoV-2 PCR?

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