Kratzer Bernhard, Stieger Robert B, Durmus Seyma, Trapin Doris, Gattinger Pia, Ettel Paul, Sehgal Al Nasar Ahmed, Borochova Kristina, Dorofeeva Yulia, Tulaeva Inna, Grabmeier-Pfistershammer Katharina, Tauber Peter A, Gerdov Marika, Perkmann Thomas, Fae Ingrid, Wenda Sabine, Kundi Michael, Wrighton Sebastian, Fischer Gottfried F, Valenta Rudolf, Pickl Winfried F
Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Front Immunol. 2025 Oct 1;16:1672485. doi: 10.3389/fimmu.2025.1672485. eCollection 2025.
During the acute-phase of COVID-19, elevated levels of several acute-phase proteins, such as C-reactive protein (CRP), mannose-binding lectin (MBL), pentraxin 3 (PTX-3), serum amyloid A (SAA) and surfactant protein D (SP-D), are associated with severe to fatal clinical outcomes. Typically, these markers return to baseline within days after resolution of the acute infection.
In this study, we assessed the plasma levels of these proteins in a well-defined cohort of 141 COVID-19 convalescent patients 10 weeks after infection and compared them to 98 non-infected controls. In addition, we performed genetic analyses in a subgroup of patients and related the findings with structural equation modelling to disease severity.
In contrast to other acute-phase proteins, PTX-3 levels were significantly higher in severe COVID-19 convalescent patients than in the control group. Furthermore, a higher proportion of patients with severe COVID-19 exhibited PTX-3 levels above 5000 pg/ml even 10 months post-infection, compared to those with mild disease. To explore potential genetic influences, a genetic analysis was performed on all severely affected patients (n=36) and on an age- and sex-matched subset of mild COVID-19 patients (n=38). Results revealed a significantly higher frequency (p<0.0001) of the homozygous wildtype genotype of the PTX-3 SNP rs971145291 in severe (15 out of 36) versus mild (1 out of 38) COVID-19 patients. Using structural equation modelling, the association of this PTX-3 genotype and disease severity was shown to be mediated by elevated PTX-3 levels, with no contribution from other analyzed (clinical) confounders.
In summary, severe COVID-19 patients show high PTX-3 serum levels which may be influenced by genetic predisposition, specifically the absence of the rs971145291 SNP variant. PTX-3 may thus serve both as a biomarker for tissue damage and/or long-term immune activation and eventually post-COVID-19 complications.
在新冠病毒病（COVID-19）急性期，几种急性期蛋白水平升高，如C反应蛋白（CRP）、甘露糖结合凝集素（MBL）、五聚素3（PTX-3）、血清淀粉样蛋白A（SAA）和表面活性蛋白D（SP-D），与严重至致命的临床结局相关。通常，这些标志物在急性感染消退后的数天内恢复至基线水平。
在本研究中，我们评估了141例COVID-19康复患者在感染10周后血浆中这些蛋白的水平，并将其与98例未感染的对照组进行比较。此外，我们对部分患者进行了基因分析，并通过结构方程模型将研究结果与疾病严重程度相关联。
与其他急性期蛋白不同，PTX-3水平在重症COVID-19康复患者中显著高于对照组。此外，与轻症患者相比，即使在感染10个月后，仍有更高比例的重症COVID-19患者PTX-3水平高于5000 pg/ml。为探究潜在的遗传影响因素，我们对所有重症患者（n = 36）以及年龄和性别匹配的轻症COVID-19患者亚组（n = 38）进行了基因分析。结果显示，PTX-3单核苷酸多态性（SNP）rs971145291的纯合野生型基因型在重症COVID-19患者（36例中有15例）中的频率显著高于轻症患者（38例中有1例）（p < 0.0001）。通过结构方程模型，该PTX-3基因型与疾病严重程度的关联显示是由PTX-3水平升高介导的，其他分析的（临床）混杂因素无贡献。
总之，重症COVID-19患者显示出较高的PTX-3血清水平，这可能受遗传易感性影响，特别是rs971145291 SNP变异的缺失。因此，PTX-3可能既是组织损伤和/或长期免疫激活的生物标志物，也是COVID-19后并发症的最终生物标志物。
