Quantitative and Ultrasensitive In-situ Immunoassay Technology for SARS-CoV-2 Detection in Saliva

Lee, Luke P.; Liu, Fei; Chen, Yuchao; Roma, Gianluca

doi:10.21203/rs.3.rs-138025/v1

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…Our results show a clear advantage of NPS as a specimen in combination with the probed antigen test. This is in concordance with other antigen test systems which, in general, have shown lower sensitivity compared to NPS [ 35 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. One of the automated antigen tests previously evaluated for saliva samples is the Lumipulse G SARS-CoV-2 Ag assay, a chemiluminescent enzyme immunoassay which received the CE marking for qualitative and quantitative detection of the SARS-CoV-2 N antigen on both saliva and NPS samples.…”

Section: Discussionsupporting

confidence: 89%

“…As we showed, conducting head-to-head comparisons of NPS and saliva for both PCR and antigen test is critical to dissect if matrix effects in saliva exist. As only few studies have assessed saliva in the context of SARS-CoV-2 antigen tests, and those that have, recorded variable results [ 35 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ], it can currently not be excluded that antigen tests generally show a reduced sensitivity across diverse tests systems. Alternatively, these effects may be test-dependent and can be modest enough to allow application in mass testing as a recent study suggests [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs

et al. 2021

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Early identification and isolation of SARS-CoV-2-infected individuals is central to contain the COVID-19 pandemic. Nasopharyngeal swabs (NPS) serve as a specimen for detection by RT-PCR and rapid antigen screening tests. Saliva has been confirmed as a reliable alternative specimen for RT-PCR and has been shown to be valuable for diagnosing children and in repetitive mass testing due to its non-invasive collection. Combining the advantages of saliva with those of antigen tests would be highly attractive to further increase test capacities. Here, we evaluated the performance of the Elecsys SARS-CoV-2 Antigen assay (Roche) in RT-PCR-positive paired NPS and saliva samples (N = 87) and unpaired NPS (N = 100) with confirmed SARS-CoV-2 infection (Roche cobas SARS-CoV-2 IVD test). We observed a high positive percent agreement (PPA) of the antigen assay with RT-PCR in NPS, reaching 87.2% across the entire cohort, whereas the overall PPA for saliva was insufficient (40.2%). At Ct values ≤ 28, PPA were 100% and 91.2% for NPS and saliva, respectively. At lower viral loads, the sensitivity loss of the antigen assay in saliva was striking. At Ct values ≤ 35, the PPA for NPS remained satisfactory (91.5%), whereas the PPA for saliva dropped to 46.6%. In conclusion, saliva cannot be recommended as a reliable alternative to NPS for testing with the Elecsys Anti-SARS-CoV-2 Antigen assay. As saliva is successfully used broadly in combination with RT-PCR testing, it is critical to create awareness that suitability for RT-PCR cannot be translated to implementation in antigen assays without thorough evaluation of each individual test system.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs

et al. 2021

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Integrated Point-of-Care Molecular Diagnostic Devices for Infectious Diseases

2021

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Conspectus The global outbreaks of deadly infectious diseases caused by pathogenic microorganisms have threatened public health worldwide and significantly motivated scientists to satisfy an urgent need for a rapid and accurate detection of pathogens. Traditionally, the culture-based technique is considered as the gold standard for pathogen detection, yet it has a long turnaround time due to the overnight culturing and pathogen isolation. Alternatively, nucleic acid amplification tests provide a relatively shorter turnaround time to identify whether pathogens exist in individuals with high sensitivity and high specificity. In most cases, nucleic acid amplification tests undergo three steps: sample preparation, nucleic acid amplification, and signal transduction. Despite the explosive advancement in nucleic acid amplification and signal transduction technologies, the complex and labor-intensive sample preparation steps remain a bottleneck to create a transformative integrated point-of-care (POC) molecular diagnostic device. Researchers have attempted to simplify and integrate the sample preparations for nucleic acid-based molecular diagnostic devices with innovative progress in integration strategies, engineered materials, reagent storages, and fluid actuation. Therefore, understanding the know-how and obtaining truthful knowledge of existing integrated POC molecular diagnostic devices comprising sample preparations, nucleic acid amplification, and signal transduction can generate innovative solutions to achieve personalized precision medicine and improve global health. In this Account, we discuss the challenges of automated sample preparation solutions integrated with nucleic acid amplification and signal transduction for rapid and precise home diagnostics. Blood, nasal swab, saliva, urine, and stool are emphasized as the most commonly used clinical samples for integrated POC molecular diagnostics of infectious diseases. Even though these five types of samples possess relatively correlated biomarkers due to the human body’s circulatory system, each shows unique properties and exclusive advantages for molecular diagnostics in specific situations, which are included in this Account. We examine different integrated POC devices for sample preparation, which includes pathogen isolation and enrichment from the crude sample and nucleic acid purification from isolated pathogens. We present the promising on-chip integration approaches for nucleic acid amplification. We also investigate the on-chip integration methods for reagent storage, which is crucial to simplify the manual operation for end-users. Finally, we present several integrated POC molecular diagnostic devices for infectious diseases. The integrated sample preparation and nucleic acid amplification approach reviewed here can potentially impact the next generation of POC molecular home diagnostic chips, which will significantly impact public health, emergency medicine, and global biosecurity.

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The accuracy of novel antigen rapid diagnostics for SARS-CoV-2: a living systematic review and meta-analysis

Brümmer

Katzenschlager

Gaeddert

et al. 2021

Preprint

102

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Background: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being inte-grated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensi-tivity and specificity) of commercially available Ag-RDTs. Methods: We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FINDdx) for publications up until December 11th, 2020. Descriptive analyses of all studies were performed and when more than four studies were avail-able, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses ((1) performed conform with manufacturers instructions for use (IFU) or not, (2) symptomatic vs. asymptomatic, (3) duration of symptoms less than seven days vs. more than seven days, (4) Ct-value <25 vs. <30 vs. >30, (5) by sample type)) and with meta-regression. We assessed study quality and risk of bias using the QUADAS 2 assessment tool. Results: From a total of 11,715 articles, we extracted 98 analytical and clinical data sets. 74 clinical accuracy data sets were evaluated that included 31,202 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 73.8% (CI 68.6 to 78.5). If analysis was re-stricted to studies that followed the Ag-RDT manufacturers instructions using fresh upper res-piratory swab samples, the sensitivity increased to 79.1% (95%CI 75.0 to 82.8). The SD Biosensor Standard Q and Abbott Panbio showed the highest sensitivity with 81.7% and 72.7%, respectively. The best Ag-RDT performance was found with nasopharyngeal sampling (77.3%, CI 72.0 to 81.9) in comparison to other sample types (e.g., anterior nasal or mid turbinate 63.5%, CI 49.5 to 75.5). Testing in the first week from symptom onset resulted in higher sensitivity (87.5%, CI 86.0 to 89.1) compared to testing after one week (64.1%, CI 54.4 to 73.8). The tests performed markedly better on samples with lower Ct-values, i.e., <30 (87.9%, CI 86.7 to 88.8), in comparison to those with Ct >30 (47.8%, CI 41.1 to 54.5). Bias concerns were raised across all data sets, and financial support from the manufacturer was reported in 28.2% of data sets. Conclusion: As Ag-RDTs detect most cases within the first week of symptom onset and those with high viral load, they can have high utility for screening purposes in the early phase of disease, and thus can be a valuable tool to fight the spread of SARS-CoV-2. Standardization of con-duct and reporting of clinical accuracy studies would improve comparability and use of data.

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Quantitative and Ultrasensitive In-situ Immunoassay Technology for SARS-CoV-2 Detection in Saliva

Cited by 3 publications

References 24 publications

Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs

Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs

Integrated Point-of-Care Molecular Diagnostic Devices for Infectious Diseases

The accuracy of novel antigen rapid diagnostics for SARS-CoV-2: a living systematic review and meta-analysis

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