SARS-CoV-2 shifting transmission dynamics and hidden reservoirs potentially limit efficacy of public health interventions in Italy

  1. Marta Giovanetti
  2. Eleonora Cella
  3. Francesca Benedetti
  4. Brittany Rife Magalis
  5. Vagner Fonseca
  6. Silvia Fabris
  7. Giovanni Campisi
  8. Alessandra Ciccozzi
  9. Silvia Angeletti
  10. Alessandra Borsetti
  11. Vittoradolfo Tambone
  12. Caterina Sagnelli
  13. Stefano Pascarella
  14. Alberto Riva
  15. Giancarlo Ceccarelli
  16. Alessandro Marcello
  17. Taj Azarian
  18. Eduan Wilkinson
  19. Tulio de Oliveira
  20. Luiz Carlos Junior Alcantara
  21. Roberto Cauda
  22. Arnaldo Caruso
  23. Natalie E. Dean
  24. Cameron Browne
  25. Jose Lourenco
  26. Marco Salemi
  27. Davide Zella
  28. Massimo Ciccozzi

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Abstract

We investigated SARS-CoV-2 transmission dynamics in Italy, one of the countries hit hardest by the pandemic, using phylodynamic analysis of viral genetic and epidemiological data. We observed the co-circulation of multiple SARS-CoV-2 lineages over time, which were linked to multiple importations and characterized by large transmission clusters concomitant with a high number of infections. Subsequent implementation of a three-phase nationwide lockdown strategy greatly reduced infection numbers and hospitalizations. Yet we present evidence of sustained viral spread among sporadic clusters acting as “hidden reservoirs” during summer 2020. Mathematical modelling shows that increased mobility among residents eventually catalyzed the coalescence of such clusters, thus driving up the number of infections and initiating a new epidemic wave. Our results suggest that the efficacy of public health interventions is, ultimately, limited by the size and structure of epidemic reservoirs, which may warrant prioritization during vaccine deployment.

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  1. Version published to 10.1038/s42003-021-02025-0
  2. ScreenIT

    SciScore for 10.1101/2020.12.16.20248355: (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
    Each Italian sequence was used in a local alignment (BLAST) 29 search for the most (genetically) similar non-Italian sequence in the GISAID database as of Oct 31st, 2020, and linked to two reference sequences including the best match (highest E-value) with a date occurring within one month following, as well as one month prior to the sampling date of the Italian sequence (although, in some cases, only a single non-Italian reference sequence fulfilling one of the inclusion criteria could be found for multiple Italian query sequences).
    BLAST
    suggested: (BLASTX, RRID:SCR_001653)
    Sequence alignments and phylogenetic analysis: Sequences (Italian + reference strains) were aligned using MAFFT (FF-NS-2 algorithm) employing default parameters 31.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    The alignment was manually curated to optimize number and location of gaps using Aliview 32.
    Aliview
    suggested: (AliView, RRID:SCR_002780)
    Phylogenetic analysis of was performed using the maximum likelihood (ML) method implemented in IQ-TREE (version 1.6.10), employing the best-fit model of nucleotide substitution according to the Bayesian Information Criterion (BIC), as indicated by the Model Finder application implemented in IQ-TREE 34.
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)
    Molecular clock calibration and estimation of virus effective population size: ML trees were inspected in TempEst v1.5.3 for the presence of temporal signal (i.e., linear relationship between genetic distance and sampling time in the available sequences) [21].
    TempEst
    suggested: (TempEst, RRID:SCR_017304)
    The phytools package 39 in R was used for joint likelihood reconstruction of discrete ancestral origins 40 according to country (and associated uncertainty) for the most recent common ancestor (MRCA) of each transmission cluster within the ML tree (scaled in substitutions/site) for the combined dataset.
    phytools
    suggested: (phytools, RRID:SCR_015502)
    The relevant method of calculation of Re builds upon another method developed by Cori et al.52, accessible through EpiEstim R package.
    EpiEstim
    suggested: (EpiEstim, RRID:SCR_018538)

    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.

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  3. Version published to 10.1101/2020.12.16.20248355v2 on medRxiv
  4. Version published to 10.1101/2020.12.16.20248355v1 on medRxiv