Chandna Arjun, Mahajan Raman, Gautam Priyanka, Mwandigha Lazaro, Dittrich Sabine, Kumar Vikash, Osborn Jennifer, Kumar Pragya, Koshiaris Constantinos, Varghese George M, Lubell Yoel, Burza Sakib
Cambodia Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, United Kingdom.
PLOS Glob Public Health. 2023 Aug 21;3(8):e0001538. doi: 10.1371/journal.pgph.0001538. eCollection 2023.
The soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a biomarker for risk stratification of patients presenting with acute infections. However, most studies evaluating suPAR have used platform-based assays, the accuracy of which may differ from point-of-care tests capable of informing timely triage in settings without established laboratory capacity. Using samples and data collected during a prospective cohort study of 425 patients presenting with moderate Covid-19 to two hospitals in India, we evaluated the analytical performance and prognostic accuracy of a commercially-available rapid diagnostic test (RDT) for suPAR, using an enzyme-linked immunosorbent assay (ELISA) as the reference standard. Our hypothesis was that the suPAR RDT might be useful for triage of patients presenting with moderate Covid-19 irrespective of its analytical performance when compared with the reference test. Although agreement between the two tests was limited (bias = -2.46 ng/mL [95% CI = -2.65 to -2.27 ng/mL]), prognostic accuracy to predict supplemental oxygen requirement was comparable, whether suPAR was used alone (area under the receiver operating characteristic curve [AUC] of RDT = 0.73 [95% CI = 0.68 to 0.79] vs. AUC of ELISA = 0.70 [95% CI = 0.63 to 0.76]; p = 0.12) or as part of a published multivariable prediction model (AUC of RDT-based model = 0.74 [95% CI = 0.66 to 0.83] vs. AUC of ELISA-based model = 0.72 [95% CI = 0.64 to 0.81]; p = 0.78). Lack of agreement between the RDT and ELISA in our cohort warrants further investigation and highlights the importance of assessing candidate point-of-care tests to ensure management algorithms reflect the assay that will ultimately be used to inform patient care. Availability of a quantitative point-of-care test for suPAR opens the door to suPAR-guided risk stratification of patients with Covid-19 and other acute infections in settings with limited laboratory capacity.
可溶性尿激酶型纤溶酶原激活物受体（suPAR）已被提议作为急性感染患者风险分层的生物标志物。然而，大多数评估suPAR的研究都使用基于平台的检测方法，其准确性可能与能够在没有成熟实验室能力的环境中为及时分诊提供依据的即时检测不同。我们利用在印度两家医院对425例中度新冠肺炎患者进行的前瞻性队列研究中收集的样本和数据，以酶联免疫吸附测定（ELISA）作为参考标准，评估了一种市售的suPAR快速诊断检测（RDT）的分析性能和预后准确性。我们的假设是，与参考检测相比，suPAR RDT可能对中度新冠肺炎患者的分诊有用，无论其分析性能如何。尽管两种检测之间的一致性有限（偏差=-2.46 ng/mL [95%CI=-2.65至-2.27 ng/mL]），但预测补充氧气需求的预后准确性相当，无论suPAR是单独使用（RDT的受试者操作特征曲线下面积[AUC]=0.73 [95%CI=0.68至0.79]，而ELISA为0.70 [95%CI=0.63至0.76]；p=0.12）还是作为已发表的多变量预测模型的一部分（基于RDT的模型的AUC=0.74 [95%CI=0.66至0.83]，而基于ELISA的模型为0.72 [95%CI=0.64至0.81]；p=0.78）。我们队列中RDT和ELISA之间缺乏一致性值得进一步研究，并突出了评估候选即时检测以确保管理算法反映最终将用于指导患者护理的检测方法的重要性。suPAR定量即时检测的可用性为在实验室能力有限的环境中对新冠肺炎和其他急性感染患者进行suPAR指导的风险分层打开了大门。
