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: COVID-19; apoptosis; virology.
【저자키워드】 COVID-19, Apoptosis, Virology., 【초록키워드】 SARS-CoV-2, Apoptosis, Necrosis, Virology, intensive care unit, clinical trials, discharged patients, emergency department, risk stratification, Patient, ICU admission, Control, respiratory, cell death, hospitalisation, epithelial, Care, estimation, patients, mechanism, caspase, COVID-19 patients, severe disease, independent predictors, COVID-19 patient, Trigger, epithelial cell, respiratory symptoms, triggers, admitted patients, Blood samples, enzyme, Adult patients, hospitalised COVID-19 patients, multivariable logistic regression, therapeutic efficacy, blood sample, non-ICU, respiratory symptom, relative contributions, cell damage, hospitalised, controls, Intact, enrolled, collected, assays, elevated, appear, sick, presenting, relative contribution, independent predictor, patients with COVID-19, 【제목키워드】 Biomarker, cell death, quantification, cytokeratin,