Clinical and molecular characterization of COVID-19 hospitalized patients

  1. Elisa Benetti
  2. Annarita Giliberti
  3. Arianna Emiliozzi
  4. Floriana Valentino
  5. Laura Bergantini
  6. Chiara Fallerini
  7. Federico Anedda
  8. Sara Amitrano
  9. Edoardo Conticini
  10. Rossella Tita
  11. Miriana d’Alessandro
  12. Francesca Fava
  13. Simona Marcantonio
  14. Margherita Baldassarri
  15. Mirella Bruttini
  16. Maria Antonietta Mazzei
  17. Francesca Montagnani
  18. Marco Mandalà
  19. Elena Bargagli
  20. Simone Furini
  21. GEN-COVID Multicenter Study
  22. Alessandra Renieri
  23. Francesca Mari

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Abstract

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.

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  1. Version published to 10.1371/journal.pone.0242534
  2. Version published to 10.1101/2020.05.22.20108845v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.05.22.20108845: (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
    Genetic data analysis: Reads were mapped to the hg19 reference genome by the Burrow-Wheeler aligner BWA [51].
    BWA
    suggested: (BWA, RRID:SCR_010910)
    Variants were annotated by ANNOVAR [53], and with the number of articles answering the query “gene_name AND viral infection” in Pubmed, where gene_name is the name of the gene affected by the variant.
    ANNOVAR
    suggested: (ANNOVAR, RRID:SCR_012821)
    We used the ExAC database (http://exac.broadinstitute.org/), in particular the ExAC_NFE reported frequency to filter variants according to a minor allele frequency < 0.01.
    ExAC
    suggested: (ExAc, RRID:SCR_004068)
    Mutation disease database ClinVar (ncbi.nlm.nih.gov/clinvar/) was used to identify previous pathogenicity classifications and variants reported as likely benign/benign were discarded.
    ClinVar
    suggested: (ClinVar, RRID:SCR_006169)
    Finally, we selected genes involved in infection susceptibility using the term “viral infection” as Pubmed database search.
    Pubmed
    suggested: (PubMed, RRID:SCR_004846)

    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:
    We know that a possible limitation of this study is the heterogeneity of patients and controls, which are not matched for gender, major comorbidities and other clinical characteristics. For this reason, further analyses in a larger cohort of samples are mandatory in order to test this hypothesis of a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the fertile background in which additional private, rare or low frequency mutations confer to the host the most favorable environment for virus growth and organ damage.

    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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  4. Version published to 10.1101/2020.05.22.20108845v1 on medRxiv