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

Authors :: 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
Institute for Molecular Medicine Finland
University of Helsinki
Data Science Genetic Epidemiology Lab
Source :: Kleeman, S O, Cordioli, M, Timmers, P R H J, Khan, A, Tober-Lau, P, Kurth, F, Demichev, V, Meyer, H V, Wilson, J F, Ralser, M, Kiryluk, K, Ganna, A, Baillie, K & Janowitz, T 2022, ' Cystatin C is associated with adverse COVID-19 outcomes in diverse populations ', iScience, vol. 25, no. 10, 105040 . https://doi.org/10.1016/j.isci.2022.105040
Publication Year :: 2022
Publisher :: Elsevier BV, 2022.
Abstract: 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.