背景:确定COVID-19疾病会恶化的患者有助于评估他们是否应该接受重症监护,或者是否可以以较少的强度或通过门诊治疗。在临床护理中,常规实验室标记,如C反应蛋白,用于评估一个人的健康状况。
目的:评估基于常规血液的实验室检查预测SARS-CoV-2患者死亡率和严重或严重(从轻度或中度)COVID-19恶化的准确性。
方法:2022年8月25日,我们搜索了CochraneCOVID-19研究登记册,包括通过PubMed搜索各种数据库,例如MEDLINE,中部,Embase,medRxiv,和ClinicalTrials.gov.我们没有应用任何语言限制。
方法:我们纳入了所有设计的研究,这些设计对门诊就诊的参与者的预后准确性进行了估计,或因确诊SARS-CoV-2感染而被送往综合医院病房,以及基于人体血清样本库的研究。包括首次接触期间进行的所有常规血液实验室检查。我们纳入了作者提供的任何用于定义严重或危重疾病恶化的参考标准。
方法:两位综述作者从每个纳入的研究中独立提取数据,并使用预后准确性研究质量评估工具独立评估方法学质量。由于研究报告了同一测试的不同阈值,我们使用分层汇总受试者操作曲线模型进行荟萃分析,以估计SAS9.4中的汇总曲线.我们估计了SROC曲线上与纳入研究中特异性的中位数和四分位数范围边界相对应的点的灵敏度。直接和间接比较仅针对具有估计灵敏度和95%CI≥50%的特异性≥50%的生物标志物进行。计算相对诊断比值比作为这些生物标志物的相对准确度的总结。
结果:我们确定了总共64项研究,包括71,170名参与者,其中8169名参与者死亡,4031名参与者恶化至严重/危急状态。这些研究评估了53种不同的实验室测试。对于一些测试,包括相对于正常范围的增加和减少.测试及其截止值之间存在重要的异质性。没有一项纳入的研究具有低偏倚风险或对所有领域适用性的低关注。本综述中包含的测试均未显示出高敏感性或特异性,或者两者兼而有之。敏感性和特异性超过50%的五项测试是:C反应蛋白增加,中性粒细胞与淋巴细胞比率增加,淋巴细胞计数减少,D-二聚体增加,和乳酸脱氢酶增加。炎症死亡,C反应蛋白增加的总敏感性为76%(95%CI73%至79%),59%(低确定性证据)。对于恶化,中位特异性的总敏感性为78%(95%CI67%至86%),72%(非常低的确定性证据)。对于死亡或恶化的综合结果,或者两者兼而有之,中位特异性的总敏感性为70%(95%CI49%至85%),60%(非常低的确定性证据)。对于死亡率,中性粒细胞与淋巴细胞比值升高的总敏感性为69%(95%CI66%-72%),63%(非常低的确定性证据)。对于恶化,中位特异性的总敏感性为75%(95%CI59%至87%),71%(非常低的确定性证据)。对于死亡率,淋巴细胞计数降低的总敏感性为67%(95%CI56%-77%),61%(非常低的确定性证据)。对于恶化,淋巴细胞计数降低的总敏感性为69%(95%CI60%至76%),67%(非常低的确定性证据)。对于综合结果,中位特异性的总敏感性为83%(95%CI67%至92%),29%(非常低的确定性证据)。对于死亡率,乳酸脱氢酶升高的总敏感性为82%(95%CI66%-91%),60%(非常低的确定性证据)。对于恶化,乳酸脱氢酶增加的总敏感性为79%(95%CI76%至82%),66%(低确定性证据)。对于综合结果,中位特异性的总敏感性为69%(95%CI51%至82%),62%(非常低的确定性证据)。高凝状态对于死亡率,d-二聚体升高的总敏感性为70%(95%CI64%~76%),中位特异性为56%(非常低的确定性证据).对于恶化,汇总敏感性为65%(95%CI56%~74%),中位特异性为63%(非常低的确定性证据).对于综合结果,总敏感性为65%(95%CI52%~76%),中位特异性为54%(非常低的确定性证据).为了预测死亡率,与d-二聚体增加相比,中性粒细胞与淋巴细胞比率增加具有更高的准确性(RDOR(诊断赔率比)2.05,95%CI1.30至3.24),C反应蛋白增加(RDOR2.64,95%CI2.09至3.33),和淋巴细胞计数减少(RDOR2.63,95%CI1.55至4.46)。与淋巴细胞计数降低相比,D-二聚体增加具有更高的准确性(RDOR1.49,95%CI1.23至1.80),C反应蛋白增加(RDOR1.31,95%CI1.03至1.65),和乳酸脱氢酶增加(RDOR1.42,95%CI1.05至1.90)。此外,与淋巴细胞计数减少相比,乳酸脱氢酶增加具有更高的准确性(RDOR1.30,95%CI1.13~1.49).为了预测严重疾病的恶化,与d-二聚体增加相比,C-反应蛋白增加具有更高的准确性(RDOR1.76,95%CI1.25至2.50)。与d-二聚体增加相比,中性粒细胞与淋巴细胞比率增加具有更高的准确性(RDOR2.77,95%CI1.58至4.84)。最后,与d-二聚体增加(RDOR2.10,95%CI1.44~3.07)和乳酸脱氢酶增加(RDOR2.22,95%CI1.52~3.26)相比,淋巴细胞计数减少具有更高的准确性.
结论:实验室测试,与高凝状态和高炎症反应相关,与其他实验室测试相比,在预测SARS-CoV-2患者的严重疾病和死亡率方面更好。然而,为了安全地排除严重的疾病,测试应具有高灵敏度(>90%),并且没有一个确定的实验室测试符合这个标准。在临床实践中,通常需要对患者的健康状况进行更全面的评估,例如,将这些实验室检查与临床症状一起纳入临床预测规则,放射学发现,和病人的特征。
Identifying patients with COVID-19 disease who will deteriorate can be useful to assess whether they should receive intensive care, or whether they can be treated in a less intensive way or through outpatient care. In clinical care, routine laboratory markers, such as C-reactive protein, are used to assess a person\'s health status.
To assess the accuracy of routine blood-based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID-19 in people with SARS-CoV-2.
On 25 August 2022, we searched the Cochrane COVID-19 Study Register, encompassing searches of various databases such as MEDLINE via PubMed, CENTRAL, Embase, medRxiv, and ClinicalTrials.gov. We did not apply any language restrictions.
We included studies of all designs that produced estimates of prognostic accuracy in participants who presented to outpatient services, or were admitted to general hospital wards with confirmed SARS-CoV-2 infection, and studies that were based on serum banks of samples from people. All routine blood-based laboratory tests performed during the first encounter were included. We included any reference standard used to define deterioration to severe or critical disease that was provided by the authors.
Two review authors independently extracted data from each included study, and independently assessed the methodological quality using the Quality Assessment of Prognostic Accuracy Studies tool. As studies reported different thresholds for the same test, we used the Hierarchical Summary Receiver Operator Curve model for meta-analyses to estimate summary curves in SAS 9.4. We estimated the sensitivity at points on the SROC curves that corresponded to the median and interquartile range boundaries of specificities in the included studies. Direct and indirect comparisons were exclusively conducted for biomarkers with an estimated sensitivity and 95% CI of ≥ 50% at a specificity of ≥ 50%. The relative diagnostic odds ratio was calculated as a summary of the relative accuracy of these biomarkers.
We identified a total of 64 studies, including 71,170 participants, of which 8169 participants died, and 4031 participants deteriorated to severe/critical condition. The studies assessed 53 different laboratory tests. For some tests, both increases and decreases relative to the normal range were included. There was important heterogeneity between tests and their cut-off values. None of the included studies had a low risk of bias or low concern for applicability for all domains. None of the tests included in this review demonstrated high sensitivity or specificity, or both. The five tests with summary sensitivity and specificity above 50% were: C-reactive protein increase, neutrophil-to-lymphocyte ratio increase, lymphocyte count decrease, d-dimer increase, and lactate dehydrogenase increase. Inflammation For mortality, summary sensitivity of a C-reactive protein increase was 76% (95% CI 73% to 79%) at median specificity, 59% (low-certainty evidence). For deterioration, summary sensitivity was 78% (95% CI 67% to 86%) at median specificity, 72% (very low-certainty evidence). For the combined outcome of mortality or deterioration, or both, summary sensitivity was 70% (95% CI 49% to 85%) at median specificity, 60% (very low-certainty evidence). For mortality, summary sensitivity of an increase in neutrophil-to-lymphocyte ratio was 69% (95% CI 66% to 72%) at median specificity, 63% (very low-certainty evidence). For deterioration, summary sensitivity was 75% (95% CI 59% to 87%) at median specificity, 71% (very low-certainty evidence). For mortality, summary sensitivity of a decrease in lymphocyte count was 67% (95% CI 56% to 77%) at median specificity, 61% (very low-certainty evidence). For deterioration, summary sensitivity of a decrease in lymphocyte count was 69% (95% CI 60% to 76%) at median specificity, 67% (very low-certainty evidence). For the combined outcome, summary sensitivity was 83% (95% CI 67% to 92%) at median specificity, 29% (very low-certainty evidence). For mortality, summary sensitivity of a lactate dehydrogenase increase was 82% (95% CI 66% to 91%) at median specificity, 60% (very low-certainty evidence). For deterioration, summary sensitivity of a lactate dehydrogenase increase was 79% (95% CI 76% to 82%) at median specificity, 66% (low-certainty evidence). For the combined outcome, summary sensitivity was 69% (95% CI 51% to 82%) at median specificity, 62% (very low-certainty evidence). Hypercoagulability For mortality, summary sensitivity of a d-dimer increase was 70% (95% CI 64% to 76%) at median specificity of 56% (very low-certainty evidence). For deterioration, summary sensitivity was 65% (95% CI 56% to 74%) at median specificity of 63% (very low-certainty evidence). For the combined outcome, summary sensitivity was 65% (95% CI 52% to 76%) at median specificity of 54% (very low-certainty evidence). To predict mortality, neutrophil-to-lymphocyte ratio increase had higher accuracy compared to d-dimer increase (RDOR (diagnostic Odds Ratio) 2.05, 95% CI 1.30 to 3.24), C-reactive protein increase (RDOR 2.64, 95% CI 2.09 to 3.33), and lymphocyte count decrease (RDOR 2.63, 95% CI 1.55 to 4.46). D-dimer increase had higher accuracy compared to lymphocyte count decrease (RDOR 1.49, 95% CI 1.23 to 1.80), C-reactive protein increase (RDOR 1.31, 95% CI 1.03 to 1.65), and lactate dehydrogenase increase (RDOR 1.42, 95% CI 1.05 to 1.90). Additionally, lactate dehydrogenase increase had higher accuracy compared to lymphocyte count decrease (RDOR 1.30, 95% CI 1.13 to 1.49). To predict deterioration to severe disease, C-reactive protein increase had higher accuracy compared to d-dimer increase (RDOR 1.76, 95% CI 1.25 to 2.50). The neutrophil-to-lymphocyte ratio increase had higher accuracy compared to d-dimer increase (RDOR 2.77, 95% CI 1.58 to 4.84). Lastly, lymphocyte count decrease had higher accuracy compared to d-dimer increase (RDOR 2.10, 95% CI 1.44 to 3.07) and lactate dehydrogenase increase (RDOR 2.22, 95% CI 1.52 to 3.26).
Laboratory tests, associated with hypercoagulability and hyperinflammatory response, were better at predicting severe disease and mortality in patients with SARS-CoV-2 compared to other laboratory tests. However, to safely rule out severe disease, tests should have high sensitivity (> 90%), and none of the identified laboratory tests met this criterion. In clinical practice, a more comprehensive assessment of a patient\'s health status is usually required by, for example, incorporating these laboratory tests into clinical prediction rules together with clinical symptoms, radiological findings, and patient\'s characteristics.