Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
School of Medicine, University of Nairobi, Nairobi, Kenya.
J Clin Pathol. 2022 Jun;75(6):410-415. doi: 10.1136/jclinpath-2020-207242. Epub 2021 Mar 31.
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.
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.
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).
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.
SARS-CoV-2 引发细胞损伤和坏死的机制尚未完全阐明。我们试图定量检测 COVID-19 患者上皮细胞死亡，并评估细胞凋亡和坏死的相对贡献。
前瞻性采集成年急诊患者的血液样本。使用 M30 和 M65 酶测定法分别测定 caspase 切割（凋亡）和总细胞角蛋白 18（CK-18）（总细胞死亡）的循环水平。通过从 M65 中减去 M30 水平来估计完整的 CK-18（坏死）。
共纳入 52 例 COVID-19 患者和 27 例匹配的疾病对照组（有呼吸系统症状但不是 COVID-19 引起）。与疾病对照组相比，COVID-19 患者的 M65（p=0.046，总细胞死亡）和 M30（p=0.0079，凋亡）水平更高。住院 COVID-19 患者的 M65（p=0.014）和完整的 CK-18（p=0.004，坏死）水平高于出院患者。入住重症监护病房（ICU）的 COVID-19 患者的 M65（p=0.004）、M30（p=0.004）和完整的 CK-18（p=0.033）水平高于住院非 ICU 患者。在多变量逻辑回归中，M65、M30 和完整 CK-18 水平升高与 ICU 入院的可能性增加相关（OR=22.05，p=0.014，OR=19.71，p=0.012 和 OR=14.12，p=0.016）。
坏死似乎是住院的主要驱动因素，而凋亡和坏死似乎是 ICU 入院的驱动因素。CK-18 水平升高是严重疾病的独立预测因子，可用于 COVID-19 患者的风险分层，并在 COVID-19 临床试验的早期阶段评估治疗效果。
