Genetic Examination of Hematological Parameters in SARS-CoV-2 Infection and COVID-19

  1. Bryce Rowland
  2. Quan Sun
  3. Wanjiang Wang
  4. Tyne Miller-Fleming
  5. Nancy Cox
  6. Misa Graff
  7. Annika Faucon
  8. Megan M. Shuey
  9. Elizabeth E. Blue
  10. Paul Auer
  11. Yun Li
  12. Vijay G. Sankaran
  13. Alexander P. Reiner
  14. Laura M. Raffield
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Abstract

Background

People hospitalized with COVID-19 often exhibit hematological alterations, such as lower lymphocyte and platelet counts, which have been reported to associate with disease prognosis. It is unclear whether inter-individual variability in baseline hematological parameters prior to acute infection influences risk of SARS-CoV-2 infection and progression to severe COVID-19.

Methods

We assessed the association of blood cell counts and indices with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we used summary statistics from genome-wide association studies to assess the shared genetic architecture of baseline blood cell counts and indices on COVID-19 outcomes.

Results

We observed inconsistent associations between measured blood cell indices and both SARS-CoV-2 infection and COVID-19 hospitalization in UK Biobank and VUMC SD. In Mendelian randomization analyses using genetic summary statistics, no putative causal relationships were identified between COVID-19 related outcomes and hematological indices after adjusting for multiple testing. We observed overlapping genetic association signals between hematological parameters and COVID-19 traits. For example, we observed overlap between infection susceptibility-associated variants atPPP1R15Aand red blood cell parameters, and between disease severity-associated variants atTYK2and lymphocyte and platelet phenotypes.

Conclusions

We did not find convincing evidence of a relationship between baseline hematological parameters and susceptibility to SARS-CoV-2 infection or COVID-19 severity, though this relationship should be re-examined as larger and better-powered genetic analyses of SARS-CoV-2 infection and severe COVID-19 become available.

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