Reliability of Self-Sampling for Accurate Assessment of Respiratory Virus Viral and Immunologic Kinetics

  1. Alpana Waghmare
  2. Elizabeth M Krantz
  3. Subhasish Baral
  4. Emma Vasquez
  5. Tillie Loeffelholz
  6. E Lisa Chung
  7. Urvashi Pandey
  8. Jane Kuypers
  9. Elizabeth R Duke
  10. Keith R Jerome
  11. Alexander L Greninger
  12. Daniel B Reeves
  13. Florian Hladik
  14. E Fabian Cardozo-Ojeda
  15. Michael Boeckh
  16. Joshua T Schiffer

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with mid-nasal foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate that nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

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  1. Version published to 10.1093/infdis/jiaa451
  2. ScreenIT

    SciScore for 10.1101/2020.04.03.20051706: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    SAS, version 9.4 (SAS Institute, Cary, North Carolina) and Stata, version 16.1 (StataCorp, College Station, Texas) were used for analysis.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    Our technique therefore overcomes a fundamental limitation of human immunological studies, which is the inability to sample over temporally granular time intervals at the mucosal site of viral replication. Further validation of our technique is demonstrated with mathematical modeling that links expression of certain cytokines with early and late elimination of virus. For RSV and MPV, we demonstrate that an early surge in IFNγ is coupled with elimination of a massive number of infected cells but is insufficient for complete containment of infection, which is achieved several days later concurrent with slower expansion IL-21. Notably, IL-21 has previously been identified as required for RSV elimination in murine models29-31 In our model, it induces an extremely high death rate of infected cells once above a certain concentration. Larger scale studies may be able to link surges in different cytokines with different respiratory viruses, including SARS CoV-2, and to differentiate severity using these techniques. Of particular interest is combining information on levels of local cytokine levels with viral load at presentation, along with patient metadata, to predict infection severity. There are important limitations to our study. Correlations between foam and flocked swabs were weaker at low viral loads. However, stochastic variation in low viral load samples is inherent to quantitation of viruses which replicate in mucosa. Additional variables such as storage temperature may have...

    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

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  3. Version published to 10.1101/2020.04.03.20051706v1 on medRxiv