tetano
Editor, Senior Moderator
J Med Virol
. 2020 Dec 14.
doi: 10.1002/jmv.26731. Online ahead of print.
Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures
Karoline Leuzinger[SUP] 1 2 [/SUP], Rainer Gosert[SUP] 1 [/SUP], Kirstine K S?gaard[SUP] 3 4 [/SUP], Klaudia Naegele[SUP] 1 [/SUP], Julia Bielicki[SUP] 5 [/SUP], Tim Roloff[SUP] 3 4 [/SUP], Roland Bingisser[SUP] 6 [/SUP], Christian H Nickel[SUP] 6 [/SUP], Nina Khanna[SUP] 7 [/SUP], Sarah Tschudin Sutter[SUP] 7 [/SUP], Andreas F Widmer[SUP] 7 [/SUP], Katharina Rentsch[SUP] 8 [/SUP], Hans Pargger[SUP] 9 [/SUP], Martin Siegemund[SUP] 9 [/SUP], Daiana Stolz[SUP] 10 [/SUP], Michael Tamm[SUP] 10 [/SUP], Stefano Bassetti[SUP] 11 [/SUP], Michael Osthoff[SUP] 11 [/SUP], Manuel Battegay[SUP] 7 [/SUP], Adrian Egli[SUP] 3 4 [/SUP], Hans H Hirsch[SUP] 1 2 7 [/SUP]
Affiliations
Abstract
Objectives: Detecting SARS-CoV-2 is key to 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.
Methods: Basel-S-gene, Roche-E-gene, and Roche-cobas?6800-Target1 and Target2 were prospectively validated in 1'344 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 10-week-periods until week 23, 33, and 43, respectively.
Results: Concordant results were obtained in 1'308 cases (97%) including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman r>0.95; p<0.001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N=36, 3%) had significantly lower SARS-CoV-2-loads (p<0.001). 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 versus 52 years, p<0.001). In 261 patients providing 936 NOPS, SARS-CoV-2-loads declined by three orders of magnitude within 10 days post-diagnosis (p<0.001). 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.
Conclusion: Manual and automated assays significantly correlated qualitatively and quantitatively. Following 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. This article is protected by copyright. All rights reserved.
Keywords: Basel-SCoV2-ORF8-97bp; Basel-SCoV2-S-112bp; COVID-19; NAAT; PCR; QNAT; Severe acute respiratory syndrome coronavirus 2; bronchoalveolar lavage; tracheal secretion.
. 2020 Dec 14.
doi: 10.1002/jmv.26731. Online ahead of print.
Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures
Karoline Leuzinger[SUP] 1 2 [/SUP], Rainer Gosert[SUP] 1 [/SUP], Kirstine K S?gaard[SUP] 3 4 [/SUP], Klaudia Naegele[SUP] 1 [/SUP], Julia Bielicki[SUP] 5 [/SUP], Tim Roloff[SUP] 3 4 [/SUP], Roland Bingisser[SUP] 6 [/SUP], Christian H Nickel[SUP] 6 [/SUP], Nina Khanna[SUP] 7 [/SUP], Sarah Tschudin Sutter[SUP] 7 [/SUP], Andreas F Widmer[SUP] 7 [/SUP], Katharina Rentsch[SUP] 8 [/SUP], Hans Pargger[SUP] 9 [/SUP], Martin Siegemund[SUP] 9 [/SUP], Daiana Stolz[SUP] 10 [/SUP], Michael Tamm[SUP] 10 [/SUP], Stefano Bassetti[SUP] 11 [/SUP], Michael Osthoff[SUP] 11 [/SUP], Manuel Battegay[SUP] 7 [/SUP], Adrian Egli[SUP] 3 4 [/SUP], Hans H Hirsch[SUP] 1 2 7 [/SUP]
Affiliations
- PMID: 33314153
- DOI: 10.1002/jmv.26731
Abstract
Objectives: Detecting SARS-CoV-2 is key to 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.
Methods: Basel-S-gene, Roche-E-gene, and Roche-cobas?6800-Target1 and Target2 were prospectively validated in 1'344 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 10-week-periods until week 23, 33, and 43, respectively.
Results: Concordant results were obtained in 1'308 cases (97%) including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman r>0.95; p<0.001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N=36, 3%) had significantly lower SARS-CoV-2-loads (p<0.001). 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 versus 52 years, p<0.001). In 261 patients providing 936 NOPS, SARS-CoV-2-loads declined by three orders of magnitude within 10 days post-diagnosis (p<0.001). 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.
Conclusion: Manual and automated assays significantly correlated qualitatively and quantitatively. Following 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. This article is protected by copyright. All rights reserved.
Keywords: Basel-SCoV2-ORF8-97bp; Basel-SCoV2-S-112bp; COVID-19; NAAT; PCR; QNAT; Severe acute respiratory syndrome coronavirus 2; bronchoalveolar lavage; tracheal secretion.