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Cited by 3COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchGenetic Associations and Epidemiology

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

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Kleeman, Sam O., Cordioli, Mattia, Timmers, Paul R.H. J., Khan, Atlas, Tober-Lau, Pinkus, Kurth, Florian, Demichev, Vadim, Meyer, Hannah V. +6 more·2022·iScience
DOI 10.1016/j.isci.2022.105040PMC PMC9428108
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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.

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  • CyC levels are dynamically regulated in COVID-19 patients and correlate with in-hospital mortality.

    “have recently reported that CyC levels are dynamically regulated in COVID-19 patients and correlate with in-hospital mortality.49”

    From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [49]

    The Results report longitudinal changes in the creatinine–CyC (C2) ratio and an association between a higher ratio and COVID-specific mortality. The Methods specify that in-hospital mortality was analyzed against the C2 ratio, not CyC levels alone. Thus, the mortality association is supported, but the claim overstates what the paper shows about CyC levels themselves. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The CyC-production PGS is associated with increased odds of COVID-19 critical illness in four cohorts spanning EUR and AFR ancestry populations.

    “Consistent with this, we have found that the CyC-production PGS is associated with increased odds of COVID-19 critical illness in four cohorts spanning EUR and AFR ancestry populations.49”

    From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [49]

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Sorted by citations

Authors
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.
Affiliations
  • Cold Spring Harbor Laboratory (US)
  • University of Helsinki (FI)
  • Institute of Genetics and Cancer (GB)
  • Columbia University (US)
  • Charité – Universitätsmedizin Berlin (DE)
Corresponding author
Janowitz, Tobias
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2022-10
Volume
25
Issue
10
Pages
105040
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2022.105040
PMC
PMC9428108
OpenAlex
W4293767150
Cited by
3
References
1
Citations by year
2023: 3
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Bristol-Myers Squibb
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Novartis
  • Sanofi
  • Biogen
  • Celgene
  • Cold Spring Harbor Laboratory
  • Georgia Clinical and Translational Science Alliance
  • Northwell Health
  • Maze Therapeutics
  • Bundesministerium für Bildung und Forschung (031L0220, 161L0221)
  • Business Finland (UH4386/31/2016, 4685/31/2016, HUS 4685/31/2016)
  • National Institutes of Health (1s10od028632-01, COVID-19, UL1TR001873, 5p30ca045508-35)
  • Directorate for Biological Sciences
  • Genentech
  • Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory
  • Medical Research Council (MC_PC_17228, MC_UU_00007/10, COVID-19)
  • National Cancer Institute (P30-CA045508)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K25DK128563)
  • Janssen Biotech
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
cystatin C, COVID-19 pandemic, polygenic risk score, host genetic factors, critical illness, intensive care unit admission, plasma proteomics, prognostic factors, host response

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