Saliva as a gold-standard sample for SARS-CoV-2 detection

Tan, Steph H; Allicock, Orchid M; Armstrong-Hough, Mari; Wyllie, Anne L.

doi:10.1016/s2213-2600(21)00178-8

Cited by 101 publications

(109 citation statements)

References 15 publications

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“…This included, e.g., trachea, lung, tonsil, salivary glands, kidney, and small bowel. The presence of SARS-CoV-2 RNA in salivary glands supports the effectiveness of saliva-based SARS-CoV-2 testing that has been emerged worldwide [37]. We also showed the presence of viral RNA in non-epithelial tissues, such as lymph nodes, heart, and skeletal muscle [25,[38][39][40].…”

Section: Discussionsupporting

confidence: 80%

Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients

Wong

Klinkhammer

Djudjaj

et al. 2021

Cells

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Multiorgan tropism of SARS-CoV-2 has previously been shown for several major organs. We have comprehensively analyzed 25 different formalin-fixed paraffin-embedded (FFPE) tissues/organs from autopsies of fatal COVID-19 cases (n = 8), using histopathological assessment, detection of SARS-CoV-2 RNA using polymerase chain reaction and RNA in situ hybridization, viral protein using immunohistochemistry, and virus particles using transmission electron microscopy. SARS-CoV-2 RNA was mainly localized in epithelial cells across all organs. Next to lung, trachea, kidney, heart, or liver, viral RNA was also found in tonsils, salivary glands, oropharynx, thyroid, adrenal gland, testicles, prostate, ovaries, small bowel, lymph nodes, skin and skeletal muscle. Viral RNA was predominantly found in cells expressing ACE2, TMPRSS2, or both. The SARS-CoV-2 replicating RNA was also detected in these organs. Immunohistochemistry and electron microscopy were not suitable for reliable and specific SARS-CoV-2 detection in autopsies. These findings were validated using in situ hybridization on external COVID-19 autopsy samples (n = 9). Apart from the lung, correlation of viral detection and histopathological assessment did not reveal any specific alterations that could be attributed to SARS-CoV-2. In summary, SARS-CoV-2 and its replication could be observed across all organ systems, which co-localizes with ACE2 and TMPRSS2 mainly in epithelial but also in mesenchymal and endothelial cells. Apart from the respiratory tract, no specific (histo-)morphologic alterations could be assigned to the SARS-CoV-2 infection.

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Section: Discussionsupporting

confidence: 80%

Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients

Wong

Klinkhammer

Djudjaj

et al. 2021

Cells

View full text Add to dashboard Cite

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“…Central to this are robust sampling methods, ensuring the collection of a high-quality sample for testing. As such, a major source of the variation reported for differences in test sensitivities, arises from differences in sample collection (Wyllie et al, 2020 ; Zou et al, 2020 ; Tan et al, 2021 ). Clear collection instructions are imperative; mucus contamination can make samples difficult to work with (Landry et al, 2020 ).…”

Section: Saliva Collection and Processing Methods Impacts The Test Sensitivitymentioning

confidence: 99%

“…Compared to the gold standard nasopharyngeal swab, testing saliva for SARS-CoV-2 has been shown to have at least equal, and sometimes higher, sensitivity for detecting asymptomatic carriers (Savela et al, 2021;Yokota et al, 2021). Recent meta-analyses comparing the efficiency of PCR detection when applied to nasopharyngeal and saliva samples (Butler-Laporte et al, 2021;Cañete et al, 2021;Khiabani and Amirzade-Iranaq, 2021;Lee et al, 2021;Moreira et al, 2021), confirm the high specificity of saliva, with sensitivity positively correlating with stage of infection (i.e., early) and sampling technique (Tan et al, 2021).…”

Section: Saliva For Sars-cov-2 Infection Diagnosismentioning

confidence: 99%

Testing Saliva to Reveal the Submerged Cases of the COVID-19 Iceberg

et al. 2021

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“…Testing for SARS-CoV-2 in saliva mitigates many of the challenges associated with NPS sampling ( Tan et al , 2021 ; Vaz et al , 2020 ; Wyllie et al , 2020 ). Although various different protocols for SARS-CoV-2 testing in saliva have been proposed, including colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) and lateral flow assays ( Faustini et al , 2020 ; Lalli et al , 2021 ), RT-qPCR is the most common used modality ( Caulley et al , 2021 ; Migueres et al , 2020 ; Teo et al , 2021 ) with a reported sensitivity between ~ 69 to 100% ( Azzi et al , 2020 ; Kojima et al , 2020 ; Pasomsub et al , 2021 ; Skolimowska et al , 2020 ; To et al , 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Concordance between PCR-based extraction-free saliva and nasopharyngeal swabs for SARS-CoV-2 testing

et al. 2021

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Introduction: Saliva represents a less invasive alternative to nasopharyngeal swab (NPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. SalivaDirect is a nucleic acid extraction-free method for detecting SARS-CoV2 in saliva specimens. Studies evaluating the concordance of gold standard NPS and newly developed SalivaDirect protocols are limited. The aim of our study was to to assess SalivaDirect as an alternative method for COVID-19 testing. Methods: Matching NPS and saliva samples were analysed from a cohort of symptomatic (n=127) and asymptomatic (n=181) participants recruited from hospital and university settings, respectively. RNA was extracted from NPS while saliva samples were subjected to the SalivaDirect protocol before RT-qPCR analysis. The presence of SARS-Cov-2 was assessed using RdRP and N1 gene targets in NPS and saliva, respectively. Results: Overall we observed 94.3% sensitivity (95% CI 87.2-97.5%), and 95.9% specificity (95% CI 92.4-97.8%) in saliva when compared to matching NPS samples. Analysis of concordance demonstrated 95.5% accuracy overall for the saliva test relative to NPS, and a very high level of agreement (κ coefficient = 0.889, 95% CI 0.833–0.946) between the two sets of specimens. Fourteen of 308 samples were discordant, all from symptomatic patients. Ct values were >30 in 13/14 and >35 in 6/14 samples. No significant difference was found in the Ct values of matching NPS and saliva sample (p=0.860). A highly significant correlation (r = 0.475, p<0.0001) was also found between the Ct values of the concordant positive saliva and NPS specimens. Conclusions: Use of saliva processed according to the SalivaDirect protocol represents a valid method to detect SARS-CoV-2. Accurate and less invasive saliva screening is an attractive alternative to current testing methods based on NPS and would afford greater capacity to test asymptomatic populations especially in the context of frequent testing.

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Saliva as a gold-standard sample for SARS-CoV-2 detection

Cited by 101 publications

References 15 publications

Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients

Multisystemic Cellular Tropism of SARS-CoV-2 in Autopsies of COVID-19 Patients

Testing Saliva to Reveal the Submerged Cases of the COVID-19 Iceberg

Concordance between PCR-based extraction-free saliva and nasopharyngeal swabs for SARS-CoV-2 testing

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