Cystatin C is associated with adverse COVID-19 outcomes in diverse populations
Sam O. Kleeman,
Mattia Cordioli,
Paul R.H. J. Timmers,
Atlas Khan,
Pinkus Tober-Lau,
Florian Kurth,
Vadim Demichev,
Hannah V. Meyer,
James F. Wilson,
Markus Ralser,
Krzysztof Kiryluk,
Andrea Ganna,
Kenneth Baillie,
Tobias Janowitz
Affiliations
Sam O. Kleeman
Cold Spring Harbor Laboratory, Cold Spring Harbor, One Bungtown Road, New York, NY 11724, USA
Mattia Cordioli
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
Paul R.H. J. Timmers
MRC Human Genetics Unit, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK
Atlas Khan
Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
Pinkus Tober-Lau
Department of Biochemistry, Charité – Universitätsmedizin Berlin, Germany
Florian Kurth
Department of Biochemistry, Charité – Universitätsmedizin Berlin, Germany
Vadim Demichev
Department of Biochemistry, Charité – Universitätsmedizin Berlin, Germany
Hannah V. Meyer
Cold Spring Harbor Laboratory, Cold Spring Harbor, One Bungtown Road, New York, NY 11724, USA
James F. Wilson
MRC Human Genetics Unit, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK
Markus Ralser
Department of Biochemistry, Charité – Universitätsmedizin Berlin, Germany
Krzysztof Kiryluk
Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
Andrea Ganna
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
Kenneth Baillie
MRC Human Genetics Unit, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
Tobias Janowitz
Cold Spring Harbor Laboratory, Cold Spring Harbor, One Bungtown Road, New York, NY 11724, USA; Corresponding author
Summary: COVID-19 has highly variable clinical courses. The search for prognostic host factors for COVID-19 outcome is a priority. We performed logistic regression for ICU admission against a polygenic score (PGS) for Cystatin C (CyC) production in patients with COVID-19. We analyzed the predictive value of longitudinal plasma CyC levels in an independent cohort of patients hospitalized with COVID-19. In four cohorts spanning European and African ancestry populations, we identified a significant association between CyC-production PGS and odds of critical illness (n cases=2,319), with the strongest association captured in the UKB cohort (OR 2.13, 95% CI 1.58-2.87, p=7.12e-7). Plasma proteomics from an independent cohort of hospitalized COVID-19 patients (n cases = 131) demonstrated that CyC production was associated with COVID-specific mortality (p=0.0007). Our findings suggest that CyC may be useful for stratification of patients and it has functional role in the host response to COVID-19.
