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Cystatin C is associated with adverse COVID-19 outcomes in diverse populations

Sam O Kleeman1, Mattia Cordioli2, Paul R H J Timmers3,4

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, One Bungtown Road, New York, NY 11724, USA.

Iscience
|September 5, 2022
PubMed

Insights

A polygenic score for Cystatin C (CyC) production is linked to critical COVID-19 illness. Longitudinal CyC levels also predict COVID-19 mortality, suggesting CyC

Area of Science:

  • Genetics
  • Immunology
  • Infectious Diseases

Background:

  • COVID-19 presents with diverse clinical outcomes, necessitating prognostic host factor identification.
  • Understanding host factors is crucial for predicting severe COVID-19 and guiding patient management.

Purpose of the Study:

  • To investigate the association between a polygenic score (PGS) for Cystatin C (CyC) production and critical illness in COVID-19 patients.
  • To evaluate the predictive value of longitudinal plasma CyC levels for COVID-19 outcomes, including mortality.

Main Methods:

  • Logistic regression analysis was used to assess the association between CyC-production PGS and ICU admission across four cohorts.
  • Plasma proteomics and longitudinal CyC levels were analyzed in independent cohorts of hospitalized COVID-19 patients.

Main Results:

  • A significant association was found between CyC-production PGS and the odds of critical COVID-19 illness across diverse populations.
  • The strongest association was observed in the UK Biobank cohort (OR 2.13, p=7.12e-7).
  • Plasma CyC levels were significantly associated with COVID-19 specific mortality (p=0.0007) in hospitalized patients.

Conclusions:

  • Cystatin C (CyC) production-related genetic factors are associated with severe COVID-19 outcomes.
  • Plasma CyC levels may serve as a prognostic biomarker for stratifying COVID-19 patients.
  • CyC appears to play a functional role in the host's response to SARS-CoV-2 infection.

Keywords:
Virologyhuman metabolism

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