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Cytokeratin 18 cell death assays as biomarkers for quantification of apoptosis and necrosis in COVID-19: a prospective, observational study.
Henry, Brandon Michael; Cheruiyot, Isaac; Benoit, Stefanie W; Sanchis-Gomar, Fabian; Lippi, Giuseppe; Benoit, Justin.
  • Henry BM; Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Brandon.henry@cchmc.org.
  • Cheruiyot I; School of Medicine, University of Nairobi, Nairobi, Kenya.
  • Benoit SW; Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Sanchis-Gomar F; Department of Pediatrics, University of Cincinnati, College of Medicine, Ohio, Cincinnati, USA.
  • Lippi G; Department of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
  • Benoit J; Department of Physiology, Faculty of Medicine, University of Valencia and INCLIVA Biomedical Research Institute, Valencia, Spain.
J Clin Pathol ; 75(6): 410-415, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1166552
ABSTRACT

BACKGROUND:

The mechanism by which SARS-CoV-2 triggers cell damage and necrosis are yet to be fully elucidated. We sought to quantify epithelial cell death in patients with COVID-19, with an estimation of relative contributions of apoptosis and necrosis.

METHODS:

Blood samples were collected prospectively from adult patients presenting to the emergency department. Circulating levels of caspase-cleaved (apoptosis) and total cytokeratin 18 (CK-18) (total cell death) were determined using M30 and M65 enzyme assays, respectively. Intact CK-18 (necrosis) was estimated by subtracting M30 levels from M65.

RESULTS:

A total of 52 COVID-19 patients and 27 matched sick controls (with respiratory symptoms not due to COVID-19) were enrolled. Compared with sick controls, COVID-19 patients had higher levels of M65 (p = 0.046, total cell death) and M30 (p = 0.0079, apoptosis). Hospitalised COVID-19 patients had higher levels of M65 (p= 0.014) and intact CK-18 (p= 0.004, necrosis) than discharged patients. Intensive care unit (ICU)-admitted COVID-19 patients had higher levels of M65 (p= 0.004), M30 (p= 0.004) and intact CK-18 (p= 0.033) than hospitalised non-ICU admitted patients. In multivariable logistic regression, elevated levels of M65, M30 and intact CK-18 were associated with increased odds of ICU admission (OR=22.05, p=0.014, OR=19.71, p=0.012 and OR=14.12, p=0.016, respectively).

CONCLUSION:

Necrosis appears to be the main driver of hospitalisation, whereas apoptosis and necrosis appear to drive ICU admission. Elevated levels CK-18 levels are independent predictors of severe disease, and could be useful for risk stratification of COVID-19 patients and in assessment of therapeutic efficacy in early-phase COVID-19 clinical trials.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Keratin-18 / COVID-19 Type of study: Cohort study / Diagnostic study / Observational study / Prognostic study Limits: Adult / Humans Language: English Journal: J Clin Pathol Year: 2022 Document Type: Article Affiliation country: Jclinpath-2020-207242

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Keratin-18 / COVID-19 Type of study: Cohort study / Diagnostic study / Observational study / Prognostic study Limits: Adult / Humans Language: English Journal: J Clin Pathol Year: 2022 Document Type: Article Affiliation country: Jclinpath-2020-207242