• Karoline Leuzinger, Rainer Gosert, Kirstine K Søgaard, Klaudia Naegele, Julia Bielicki, Tim Roloff, Roland Bingisser, Christian H Nickel, Nina Khanna, SutterSarah TschudinSTInfectious Diseases & Hospital Epidemiology, Basel, Switzerland., Andreas F Widmer, Katharina Rentsch, Hans Pargger, Martin Siegemund, Daiana Stolz, Michael Tamm, Stefano Bassetti, Michael Osthoff, Manuel Battegay, Adrian Egli, and Hans H Hirsch.
• Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
• J. Med. Virol. 2021 Apr 1; 93 (4): 2374-2384.

ObjectivesDetecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures.MethodsBasel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively.ResultsConcordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively.ConclusionManual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.© 2020 Wiley Periodicals LLC.

39 keywords...

hide…