Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

  1. Ana Teresa Freitas
  2. Conceição Calhau
  3. Gonçalo Antunes
  4. Beatriz Araújo
  5. Matilde Bandeira
  6. Sofia Barreira
  7. Filipa Bazenga
  8. Sandra Braz
  9. Daniel Caldeira
  10. Susana Constantino Rosa Santos
  11. Ana Faria
  12. Daniel Faria
  13. Marta Fraga
  14. Beatriz Nogueira-Garcia
  15. Lúcia Gonçalves
  16. Pavlo Kovalchuk
  17. Luísa Lacerda
  18. Hugo Lopes
  19. Daniel Luís
  20. Fábio Medeiros
  21. Ana M. P. Melo
  22. José Melo-Cristino
  23. Ana Miranda
  24. Clara Pereira
  25. Ana Teresa Pinto
  26. João Pinto
  27. Helena Proença
  28. Angélica Ramos
  29. João P. R. Rato
  30. Filipe Rocha
  31. Júlio César Rocha
  32. André Moreira-Rosário
  33. Helena Vazão
  34. Yuliya Volovetska
  35. João-Tiago Guimarães
  36. Fausto J. Pinto

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Abstract

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity ( p  = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D ( p  = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes ( p  = 1.5e−4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.

Trial registration: NCT04370808.

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  1. Version published to 10.1038/s41598-021-99952-z
  2. ScreenIT

    SciScore for 10.1101/2021.03.22.21254032: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Genotyping: All patients signed an informed consent to perform a genetic test for the analysis of 18 genetic variants that play a role in vitamin D metabolism, transport, degradation and downstream pathways.
    IRB: Study approval: This project was approved by the Ethics Committee of Hospital de Santa Maria in Lisbon and Hospital de São João in Oporto.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data management: Clinical history, genotypic and phenotypic data, stored at the e-CRF, were collected and managed using REDCap electronic data capture tools (20) hosted by BioData.pt (https://biodata.pt/), the Portuguese distributed infrastructure for biological data, at INESC-ID research institute.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Vitamin D polymorphisms prevalence in different populations was obtained from 1000 Genomes database (https://www.internationalgenome.org/) and from HeartGenetics’s research database for the Portuguese population, with more than 8,000 Portuguese individuals.
    1000 Genomes
    suggested: (1000 Genomes Project and AWS, RRID:SCR_008801)

    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: 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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04370808Not yet recruitingVITACOV: Vitamin D Polymorphisms and Severity of COVID-19 In…

    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 10.1101/2021.03.22.21254032 on medRxiv