Siwy Justyna, Keller Felix, Banasik Mirosław, Peters Björn, Dudoignon Emmanuel, Mebazaa Alexandre, Gülmez Dilara, Spasovski Goce, Lazo Mercedes Salgueira, Rajzer Marek W, Fuławka Łukasz, Dzitkowska-Zabielska Magdalena, Mischak Harald, Hecking Manfred, Beige Joachim, Wendt Ralph
Mosaiques Diagnostics GmbH, 30659 Hannover, Germany.
Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, 6020 Innsbruck, Austria.
Biomedicines. 2024 Sep 13;12(9):2090. doi: 10.3390/biomedicines12092090.
BACKGROUND/OBJECTIVES: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity; however, this topic has not been studied in detail. Therefore, within this study, the mortality risk post-acute COVID-19 in the CRIT-COV-U cohort was investigated.
Survival data from 651 patients that survived an acute phase of COVID-19 were retrieved and the association between urinary peptides and future death was assessed. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched COVID-19-negative controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomic datasets.
Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than COVID-19-negative controls, particularly evident in younger individuals (<65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease but also beyond for a period of about one year. In our study, we were further able to identify 201 urinary peptides linked to mortality. These peptides are fragments of albumin, alpha-2-HS-glycoprotein, apolipoprotein A-I, beta-2-microglobulin, CD99 antigen, various collagens, fibrinogen alpha, polymeric immunoglobulin receptor, sodium/potassium-transporting ATPase, and uromodulin and were integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death.
The peptide-based classifier demonstrated significant predictive value for mortality in post-acute COVID-19 patients, highlighting the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. By utilizing these defined biomarkers in the clinic, risk stratification, monitoring, and personalized interventions can be significantly improved. Our data also suggest that mortality should be considered as one possible symptom or a consequence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.
背景/目的：新型冠状病毒2（SARS-CoV-2）感染后的生存前景可能超出急性期，受年龄、健康状况和感染严重程度等多种因素影响；然而，这一主题尚未得到详细研究。因此，在本研究中，我们调查了CRIT-COV-U队列中急性COVID-19后患者的死亡风险。
检索了651例度过COVID-19急性期患者的生存数据，并评估尿肽与未来死亡之间的关联。收集了来自六个国家截至2023年12月的数据，将死亡率趋势与年龄和性别匹配的COVID-19阴性对照进行比较。使用现有的尿肽组数据集开发并验证了一个死亡预测分类器。
值得注意的是，13.98%的COVID-19后患者在随访期间死亡，死亡率显著高于COVID-19阴性对照，在年轻个体（<65岁）中尤为明显。这些数据首次表明，SARS-CoV-2感染不仅在疾病急性期会显著增加死亡风险，而且在之后约一年的时间内也是如此。在我们的研究中，我们还能够识别出201种与死亡相关的尿肽。这些肽是白蛋白、α-2-HS-糖蛋白、载脂蛋白A-I、β-2-微球蛋白、CD99抗原、各种胶原蛋白、纤维蛋白原α、聚合免疫球蛋白受体、钠/钾转运ATP酶和尿调节蛋白的片段，并将它们整合到一个预测分类器（DP201）中。较高的DP201评分以及年龄和体重指数显著预测了死亡。
基于肽的分类器对急性COVID-19后患者的死亡具有显著的预测价值，突出了尿肽在预测急性COVID-19后死亡率方面的实用性，为靶向干预提供了见解。通过在临床中利用这些已定义的生物标志物，可以显著改善风险分层、监测和个性化干预。我们的数据还表明，死亡应被视为SARS-CoV-2感染急性后遗症的一种可能症状或后果，而这一事实目前被忽视了。
