OBJECTIVES: Widespread SARS-CoV-2 testing is invaluable for identifying asymptomatic/pre-symptomatic individuals. There remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests suitable for frequent mass testing. Compared to nasopharyngeal (NP) swab-based tests, saliva-based methods are attractive due to easier and safer sampling. Current saliva-based SARS-CoV-2 rapid antigen tests (RATs) are hindered by limited analytical sensitivity. Here, we report one of the first ultrasensitive, saliva-based SARS-CoV-2 antigen assays with an analytical sensitivity of <0.32 pg/mL, corresponding to four viral RNA copies/µL, which is comparable to that of PCR-based tests. METHODS: Using the novel electrochemiluminescence (ECL)-based immunoassay, we measured the SARS-CoV-2 nucleocapsid (N) antigen concentration in 105 salivas, obtained from non-COVID-19 and COVID-19 patients. We then verified the results with a second, independent cohort of 689 patients (3.8% SARS-CoV-2 positivity rate). We also compared our method with a widely used point-of-care rapid test. RESULTS: In the first cohort, at 100% specificity, the sensitivity was 92%. Our assay correctly identified samples with viral loads up to 35 CT cycles by saliva-based PCR. Paired NP swab-based PCR results were obtained for 86 cases. Our assay showed high concordance with saliva-based and NP swab-based PCR in samples with negative (<0.32 pg/mL) and strongly positive (>2 pg/mL) N antigen concentrations. In the second cohort, at 100% specificity, sensitivity was also 92%. Our assay is about 700-fold more sensitive than the Abbott Panbio Rapid Test. CONCLUSIONS: We demonstrated the ultrasensitivity and specificity assay and its concordance with PCR. This novel assay is especially valuable when compliance to frequent swabbing may be problematic.
OBJECTIVES: Widespread SARS-CoV-2 testing is invaluable for identifying asymptomatic/pre-symptomatic individuals. There remains a technological gap for highly reliable, easy, and quick SARS-CoV-2 diagnostic tests suitable for frequent mass testing. Compared to nasopharyngeal (NP) swab-based tests, saliva-based methods are attractive due to easier and safer sampling. Current saliva-based SARS-CoV-2 rapid antigen tests (RATs) are hindered by limited analytical sensitivity. Here, we report one of the first ultrasensitive, saliva-based SARS-CoV-2 antigen assays with an analytical sensitivity of <0.32 pg/mL, corresponding to four viral RNA copies/µL, which is comparable to that of PCR-based tests. METHODS: Using the novel electrochemiluminescence (ECL)-based immunoassay, we measured the SARS-CoV-2 nucleocapsid (N) antigen concentration in 105 salivas, obtained from non-COVID-19 and COVID-19 patients. We then verified the results with a second, independent cohort of 689 patients (3.8% SARS-CoV-2 positivity rate). We also compared our method with a widely used point-of-care rapid test. RESULTS: In the first cohort, at 100% specificity, the sensitivity was 92%. Our assay correctly identified samples with viral loads up to 35 CT cycles by saliva-based PCR. Paired NP swab-based PCR results were obtained for 86 cases. Our assay showed high concordance with saliva-based and NP swab-based PCR in samples with negative (<0.32 pg/mL) and strongly positive (>2 pg/mL) N antigen concentrations. In the second cohort, at 100% specificity, sensitivity was also 92%. Our assay is about 700-fold more sensitive than the Abbott Panbio Rapid Test. CONCLUSIONS: We demonstrated the ultrasensitivity and specificity assay and its concordance with PCR. This novel assay is especially valuable when compliance to frequent swabbing may be problematic.
Authors: Jacqueline Dinnes; Pawana Sharma; Sarah Berhane; Susanna S van Wyk; Nicholas Nyaaba; Julie Domen; Melissa Taylor; Jane Cunningham; Clare Davenport; Sabine Dittrich; Devy Emperador; Lotty Hooft; Mariska Mg Leeflang; Matthew Df McInnes; René Spijker; Jan Y Verbakel; Yemisi Takwoingi; Sian Taylor-Phillips; Ann Van den Bruel; Jonathan J Deeks Journal: Cochrane Database Syst Rev Date: 2022-07-22
Authors: Zoran Stojanovic; Filipe Gonçalves-Carvalho; Alicia Marín; Jorge Abad Capa; Jose Domínguez; Irene Latorre; Alicia Lacoma; Cristina Prat-Aymerich Journal: ERJ Open Res Date: 2022-09-12
Authors: George B Sigal; Tanya Novak; Anu Mathew; Janet Chou; Yubo Zhang; Navaratnam Manjula; Pradeepthi Bathala; Jessica Joe; Nikhil Padmanabhan; Daniel Romero; Gabriella Allegri-Machado; Jill Joerger; Laura L Loftis; Stephanie P Schwartz; Tracie C Walker; Julie C Fitzgerald; Keiko M Tarquinio; Matt S Zinter; Jennifer E Schuster; Natasha B Halasa; Melissa L Cullimore; Aline B Maddux; Mary A Staat; Katherine Irby; Heidi R Flori; Bria M Coates; Hillary Crandall; Shira J Gertz; Adrienne G Randolph; Nira R Pollock Journal: Clin Infect Dis Date: 2022-10-12 Impact factor: 20.999