Stringer Dominic, Braude Philip, Myint Phyo K, Evans Louis, Collins Jemima T, Verduri Alessia, Quinn Terry J, Vilches-Moraga Arturo, Stechman Michael J, Pearce Lyndsay, Moug Susan, McCarthy Kathryn, Hewitt Jonathan, Carter Ben
Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
North Bristol NHS Trust, UK.
Int J Epidemiol. 2021 May 17;50(2):420-429. doi: 10.1093/ije/dyab012.
C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality.
Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell's C statistic and Akaike information criterion (AIC)].
The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable).
The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.
C反应蛋白（CRP）是一种在感染或炎症时升高的非特异性急性期反应物。较高水平表明感染更严重，并且已被用作COVID-19疾病严重程度的指标。然而，CRP作为预后标志物的证据尚未确定。本研究的目的是检查COVID-19住院患者的CRP反应，并确定入院时CRP对预测住院患者死亡率的效用。
在2020年2月27日至6月10日期间收集数据，纳入两个队列：11个医院站点收治的1564例确诊COVID-19的成年患者的COPE（老年人COVID-19）研究（测试队列）和后来的271例患者的验证队列。对入院时的CRP进行调查，并拟合有限混合模型以评估可能的潜在分布。此外，在死亡率Cox回归中分析CRP的不同预后阈值以确定临界值。使用自举法比较模型性能[Harrell's C统计量和赤池信息准则（AIC）]。
CRP的测试和验证队列分布不受年龄影响，混合模型表明呈双峰分布。CRP≥40mg/L的阈值在预测死亡率方面表现良好（并且与将CRP视为线性变量的表现相似）。
CRP的分布特征表明，≥40mg/L的最佳临界值与死亡率相关。该阈值可能有助于临床医生将CRP用作加强观察、治疗决策和高级护理计划的早期触发因素。
