Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses

  1. Karoline Leuzinger
  2. Tim Roloff
  3. Rainer Gosert
  4. Kirstin Sogaard
  5. Klaudia Naegele
  6. Katharina Rentsch
  7. Roland Bingisser
  8. Christian H Nickel
  9. Hans Pargger
  10. Stefano Bassetti
  11. Julia Bielicki
  12. Nina Khanna
  13. Sarah Tschudin Sutter
  14. Andreas Widmer
  15. Vladimira Hinic
  16. Manuel Battegay
  17. Adrian Egli
  18. Hans H Hirsch

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)–recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs.

Methods

Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2.

Results

The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%).

Conclusions

Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.

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  1. Version published to 10.1093/infdis/jiaa464
  2. ScreenIT

    SciScore for 10.1101/2020.07.07.20148163: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics statement: The study was conducted according to good laboratory practice and in accordance with the Declaration of Helsinki and national and institutional standards and was approved by the ethical committee (EKNZ 2020-00769).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Total nucleic acids (TNAs) were extracted from the UTM using the MagNA Pure 96 system and the DNA and viral NA small volume kit (Roche Diagnostics, Rotkreuz, Switzerland) or using the Abbott m2000 Realtime System and the Abbott sample preparation system reagent kit (Abbott, Baar, Switzerland).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistics and graphical presentations: All statistical data analysis was done in R (https://www.r-project.org/), and Prism (version 8; Graphpad Software, CA, USA) was used for data visualization.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    Graphpad
    suggested: (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:
    A limitation of our study is the dependence on the pre-analytic steps of NOPS sampling, especially in the light of the natural course of SARS-CoV-2 infection. We addressed this challenge through repeated instructions and video clips demonstrating the correct use of personal protection equipment, validated swab sets, and defined sampling procedures in dedicated hospital areas. However, late presentation at stages of more advanced disease manifesting in the lower respiratory tract requires testing of respiratory samples from the lower respiratory tract, while this study was restricted to the first diagnostic testing in NOPS. Early testing is clinically and epidemiologically advisable in view of high viral loads detectable already early in the course in exposed pre-symptomatic and in oligo-symptomatic persons [16, 17]. Since our diagnostic laboratory is serving both regional tertiary care centers for adults and children, we examined the age distribution of SARS-CoV-2 and CARV infection. Indeed, patients testing positive for adenovirus and respiratory syncytial virus were significantly younger and more likely to be children below the age of 5 years, among whom SARS-CoV-2 infection remained rare, in line with other studies [18, 19]. Although SARS-CoV-2 positive adults were older than patients testing positive for CARVs, the median age of >40 years in CARV-positive patients suggests that similar adult populations were at risk for established CARVs or for the novel SARS-CoV-2. Our s...

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.07.07.20148163v1 on medRxiv