Ruiz Andy, Peña-Bates Carlos, Ramon-Luing Lucero A, Baca-Nuñez Daniel, Vargas Marco Antonio, Medina-Quero Karen, Gutierrez Neptali, Vázquez-Pérez Joel A, Falfán-Valencia Ramcés, Pérez-Rubio Gloria, Di Benedetto Carolina, Buendia-Roldan Ivette, Selman Moisés, Betancur Paola, Chavez-Galan Leslie
Research Unit, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Research Unit, Escuela Militar de Graduados de Sanidad, Mexico City, Mexico.
J Cell Mol Med. 2025 Feb;29(3):e70189. doi: 10.1111/jcmm.70189.
Molecules of the tumour necrosis factor superfamily (TNFSF) are key players in immune regulation; an increase in some TNFSF molecules has been reported during severe COVID-19. In this study, we profiled and evaluated TNFSF members in the serum of COVID-19 vaccine-naïve patients to identify potential biomarkers associated with disease severity. Our data show that TRAIL serum levels are lower in severely affected patients than those mildly affected by COVID-19 (AUC 0.8, p = 0.0003). On the contrary, OPG and BAFF serum levels are higher in severe COVID-19 compared to mild COVID-19 cases (AUC 0.8, p = 0.0001; AUC 0.7, p = 0.0012; respectively) and moderate COVID-19 cases (OPG p < 0.01), BAFF (p < 0.05). At the transcriptional level, TRAIL, OPG and BAFF are elevated in severe compared to mild COVID-19 cases, with OPG and BAFF also higher in moderate compared to mild COVID-19 patients. Additionally, we found that APRIL, LIGHT, CD30L and CD40L protein-levels are higher in COVID-19 patients compared to healthy donors but not significantly different between various COVID-19 clinical statuses. Finally, we found that TNF-α, TNF-β, RANKL and TWEAK protein levels were not affected during COVID-19. Our work identifies OPG and BAFF as potential biomarkers and therapeutic targets for preventing severe COVID-19. Due to the opposite contradictory levels of TRAIL (protein/transcriptional level), its role during COVID-19 should be elucidated and clarified with more in-depth studies.
肿瘤坏死因子超家族（TNFSF）分子是免疫调节的关键参与者；据报道，在重症新型冠状病毒肺炎（COVID-19）期间，一些TNFSF分子会增加。在本研究中，我们分析并评估了未接种COVID-19疫苗患者血清中的TNFSF成员，以确定与疾病严重程度相关的潜在生物标志物。我们的数据显示，重症患者血清中的肿瘤坏死因子相关凋亡诱导配体（TRAIL）水平低于轻症COVID-19患者（曲线下面积[AUC]为0.8，p = 0.0003）。相反，与轻症COVID-19病例相比，重症COVID-19患者血清中的骨保护素（OPG）和B细胞活化因子（BAFF）水平更高（AUC分别为0.8，p = 0.0001；AUC为0.7，p = 0.0012），与中度COVID-19病例相比也更高（OPG，p < 0.01；BAFF，p < 0.05）。在转录水平上，与轻症COVID-19病例相比，重症患者中TRAIL、OPG和BAFF升高，与轻症COVID-19患者相比，中度患者中的OPG和BAFF也更高。此外，我们发现，与健康供体相比，COVID-19患者血清中的增殖诱导配体（APRIL）、淋巴毒素相关诱导配体（LIGHT）、CD30配体（CD30L）和CD40配体（CD40L）蛋白水平更高，但在不同COVID-19临床状态之间无显著差异。最后，我们发现COVID-19期间肿瘤坏死因子-α（TNF-α）、肿瘤坏死因子-β（TNF-β）、核因子κB受体活化因子配体（RANKL）和肿瘤坏死因子样弱凋亡诱导因子（TWEAK）蛋白水平未受影响。我们的研究确定OPG和BAFF为预防重症COVID-19的潜在生物标志物和治疗靶点。由于TRAIL（蛋白/转录水平）呈现相反的矛盾水平，其在COVID-19期间的作用应通过更深入的研究加以阐明。
