Cytokeratin 18 cell death assays as biomarkers for quantification of apoptosis and necrosis in COVID-19: a prospective, observational study.
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.Keywords
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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