Determinants of epidemic size and the impacts of lulls in seasonal influenza virus circulation

  1. Simon P. J. de Jong
  2. Zandra C. Felix Garza
  3. Joseph C. Gibson
  4. Sarah van Leeuwen
  5. Robert P. de Vries
  6. Geert-Jan Boons
  7. Marliek van Hoesel
  8. Karen de Haan
  9. Laura E. van Groeningen
  10. Katina D. Hulme
  11. Hugo D. G. van Willigen
  12. Elke Wynberg
  13. Godelieve J. de Bree
  14. Amy Matser
  15. Margreet Bakker
  16. Lia van der Hoek
  17. Maria Prins
  18. Neeltje A. Kootstra
  19. Dirk Eggink
  20. Brooke E. Nichols
  21. Alvin X. Han
  22. Menno D. de Jong
  23. Colin A. Russell

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Abstract

During the COVID-19 pandemic, levels of seasonal influenza virus circulation were unprecedentedly low, leading to concerns that a lack of exposure to influenza viruses, combined with waning antibody titres, could result in larger and/or more severe post-pandemic seasonal influenza epidemics. However, in most countries the first post-pandemic influenza season was not unusually large and/or severe. Here, based on an analysis of historical influenza virus epidemic patterns from 2002 to 2019, we show that historic lulls in influenza virus circulation had relatively minor impacts on subsequent epidemic size and that epidemic size was more substantially impacted by season-specific effects unrelated to the magnitude of circulation in prior seasons. From measurements of antibody levels from serum samples collected each year from 2017 to 2021, we show that the rate of waning of antibody titres against influenza virus during the pandemic was smaller than assumed in predictive models. Taken together, these results partially explain why the re-emergence of seasonal influenza virus epidemics was less dramatic than anticipated and suggest that influenza virus epidemic dynamics are not currently amenable to multi-season prediction.

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  1. Version published to 10.1038/s41467-023-44668-z
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    SciScore for 10.1101/2022.02.05.22270494: (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

    Antibodies
    SentencesResources
    Using only samples collected in the summer period potentially helps to overcome issues that could arise from the transient antibody boosts due to both infection and vaccination23.
    vaccination23
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    All four viruses were propagated on Madin-Darby Canine Kidney (MDCK) cells in infection medium, which consisted of MEM-Eagle Medium /EBSS (Lonza, Geleen, The Netherlands) supplemented with MEM Non-Essential Amino Acids (Gibco, ThermoFischer Scientific, Amsterdam, The Netherlands), penicillin (100 U/mL), streptomycin (100 g/mL), L-Glutamine (Lonza), HEPES (Lonza), and TPCKtrypsin (Sigma-Aldrich/Merck, Darmstadt, Germany).
    MDCK
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2022.02.05.22270494 on medRxiv