Kleeman Sam O, Cordioli Mattia, Timmers Paul R H J, Khan Atlas, Tober-Lau Pinkus, Kurth Florian, Demichev Vadim, Meyer Hannah V, Wilson James F, Ralser Markus, Kiryluk Krzysztof, Ganna Andrea, Baillie Kenneth, Janowitz Tobias
Cold Spring Harbor Laboratory, Cold Spring Harbor, One Bungtown Road, New York, NY 11724, USA.
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
iScience. 2022 Oct 21;25(10):105040. doi: 10.1016/j.isci.2022.105040. Epub 2022 Aug 31.
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.
新冠病毒病（COVID-19）具有高度可变的临床病程。寻找影响COVID-19预后的宿主预后因素是当务之急。我们对COVID-19患者中针对胱抑素C（CyC）产生的多基因评分（PGS）进行了入住重症监护病房（ICU）的逻辑回归分析。我们分析了纵向血浆CyC水平在独立的COVID-19住院患者队列中的预测价值。在涵盖欧洲和非洲血统人群的四个队列中，我们确定了CyC产生的PGS与危重症几率之间存在显著关联（病例数n = 2319），其中在英国生物银行（UKB）队列中关联最强（比值比OR = 2.13，95%置信区间CI 1.58 - 2.87，p = 7.12×10⁻⁷）。来自独立的COVID-19住院患者队列（病例数n = 131）的血浆蛋白质组学研究表明，CyC产生与COVID-19特异性死亡率相关（p = 0.0007）。我们的研究结果表明，CyC可能有助于对患者进行分层，并且在宿主对COVID-19的反应中具有功能性作用。
