Epidemiology and precision of SARS‐CoV‐2 detection following lockdown and relaxation measures
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Abstract
Objectives
Detecting 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.
Methods
Basel‐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.
Results
Concordant 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.
Conclusion
Manual 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.
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SciScore for 10.1101/2020.09.22.20198697: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics Statement: The study was conducted according to good laboratory practice and in accordance with the Declaration of Helsinki and national and institutional standards for laboratory quality control and was approved by the Ethical Committee of North-western and Central Switzerland (EKNZ 2020-00769). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Total nucleic acid extraction and reverse transcription quantitative nucleic acid test: Total nucleic acids (TNAs) were extracted from the UTMs lower respiratory fluids and plasma using … SciScore for 10.1101/2020.09.22.20198697: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics Statement: The study was conducted according to good laboratory practice and in accordance with the Declaration of Helsinki and national and institutional standards for laboratory quality control and was approved by the Ethical Committee of North-western and Central Switzerland (EKNZ 2020-00769). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Total nucleic acid extraction and reverse transcription quantitative nucleic acid test: Total nucleic acids (TNAs) were extracted from the UTMs lower respiratory fluids and plasma using the DNA and viral NA small volume kit on the MagNA Pure 96 system (Roche Diagnostics, Rotkreuz, Switzerland) or the Abbott sample preparation system reagent kit using the Abbott m2000 Realtime System (Abbott, Baar, Switzerland). Abbottsuggested: (Abbott, RRID:SCR_010477)Statistical analysis: All statistical data analysis was done in R (version 3.6.1; https://cran.r-project.org), and Prism (version 8; Graphpad Software, CA, USA) was used for data visualization. Prismsuggested: (PRISM, RRID:SCR_005375)Graphpadsuggested: (GraphPad, RRID:SCR_000306)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Thus, this real-life setting indicates the need for confirmatory information in up to 8% of clinical cases and point to critical limitations of large-scale screening of the general population and impact the validity of sample pooling endeavors. Both approaches are discussed for assessing periods of effective containment as well as for testing populations with difficult to define SARS-CoV-2 exposure risk such as returning travelers. In the clinical setting of patients presenting to our center, SARS-CoV-2 detection steadily declined from 9% in the validation cohort close to the peak of the first pandemic wave to an overall rate of 2% in both of our two follow-up cohorts, each covering more than 10’000 patients over 10 weeks. The epidemiologic dynamics were captured by weekly detection rates, which steadily declined to <1% and then flared up to 4%, both at approximately 6 weeks following lockdown and relaxation measures, respectively. Although we cannot define the key factors for either development, the demographics reveal a significantly younger median age of only 34 years of SARS-CoV-2 diagnosis in the follow-up cohort-2 compared to approximately 50 years in the validation and follow-up cohort-1. Although the proportion of children testing positive for SARS-CoV-2 had also significantly increased from 3% to 10%, the interquartile age range of follow-up cohort-2 indicated that the recent SARS-CoV-2 flare was mostly due to younger adults between 24 and 48 years of age. These data...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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