Wolday Dawit, Gebrehiwot Abrha G, Le Minh An Nguyen, Rameto Muhammed Ahmed, Abdella Saro, Gebreegziabxier Atsbeha, Amogne Wondwossen, Rinke de Wit Tobias F, Hailu Messay, Tollera Getachew, Tasew Geremew, Tessema Masresha, Miller Matthew, Gillgrass Amy, Bowdish Dawn M E, Kaushic Charu, Verschoor Chris P
Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
McMaster Immunology Research Centre, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Front Immunol. 2025 May 22;16:1575135. doi: 10.3389/fimmu.2025.1575135. eCollection 2025.
Little is known about the acute and long-term sequelae of COVID-19 and its pathophysiology in African patients, who are known to have a distinct immunological profile compared to Caucasian populations. Here, we established protein signatures to define severe outcomes of acute COVID-19 and determined whether unique protein signatures during the first week of acute illness predict the risk of post-acute sequelae of COVID-19 (Long COVID) in a low-income country (LIC) setting.
Using the Olink inflammatory panel, we measured the abundance of 92 proteins in the plasma of COVID-19 patients (n=55) and non-COVID-19 individuals (n=23). We investigated distinct inflammatory protein signatures in acute severe COVID-19 individuals (n=22) compared to asymptomatic or mild/moderate COVID-19 cases (n=33), and non-COVID-19 controls.
Levels of SLAMF1, CCL25, IL2RB, IL10RA, IL15RA, IL18 and CST5 were significantly upregulated in patients with critical COVID-19 illness compared to individuals negative for COVID-19. The cohort was followed for an average of 20 months, and 23 individuals developed Long COVID, based on the WHO's case definition, while 32 COVID-19 patients recovered fully. Whereas upregulated levels of SLAMF1, TNF, TSLP, IL15RA, IL18, ADA, CXCL9, CXCL10, IL17C, and NT3 at the acute phase of the illness were associated with increased Long COVID risk, upregulated TRANCE was associated with a reduced risk of developing Long COVID. Protein levels of SLAMF1, IL15RA, and IL18 associated with critical illness during the acute phase of COVID-19 also predicted Long COVID risk.
Patients with severe COVID-19 and Long COVID outcomes exhibited distinct proteomic signatures. Unravelling the pathophysiology of severe acute COVID-19 and Long COVID before its advent may contribute to designing novel interventions for diagnosing, treating, and monitoring of SARS-CoV-2 infection and its associated acute and long-term consequences.
与白种人群相比，非洲患者的免疫特征独特，但对于新冠病毒疾病（COVID-19）的急性和长期后遗症及其病理生理学，我们知之甚少。在此，我们建立了蛋白质特征来定义急性COVID-19的严重结局，并确定在低收入国家环境中，急性疾病第一周期间独特的蛋白质特征是否能预测COVID-19急性后遗症（长期新冠）的风险。
使用欧林克炎症检测板，我们测量了COVID-19患者（n = 55）和非COVID-19个体（n = 23）血浆中92种蛋白质的丰度。我们调查了急性重症COVID-19个体（n = 22）与无症状或轻/中度COVID-19病例（n = 33）以及非COVID-19对照相比不同的炎症蛋白特征。
与COVID-19阴性个体相比，重症COVID-19患者中信号淋巴细胞激活分子家族成员1（SLAMF1）、趋化因子（C-C基序）配体25（CCL25）、白细胞介素2受体β链（IL2RB）、白细胞介素10受体α链（IL10RA）、白细胞介素15受体α链（IL15RA）、白细胞介素18（IL18）和胱抑素T5（CST5）的水平显著上调。该队列平均随访20个月，根据世界卫生组织的病例定义，23人出现长期新冠，而32名COVID-19患者完全康复。疾病急性期SLAMF1、肿瘤坏死因子（TNF）、胸腺基质淋巴细胞生成素（TSLP）、IL15RA、IL18、腺苷脱氨酶（ADA）、CXC趋化因子配体9（CXCL9）、CXC趋化因子配体10（CXCL10）、白细胞介素17C和神经营养因子3（NT3）水平上调与长期新冠风险增加相关，而肿瘤坏死因子相关激活诱导细胞因子（TRANCE）上调与长期新冠发生风险降低相关。COVID-19急性期与重症疾病相关的SLAMF1、IL15RA和IL18蛋白水平也可预测长期新冠风险。
重症COVID-19和长期新冠结局的患者表现出不同的蛋白质组学特征。在严重急性COVID-19和长期新冠出现之前揭示其病理生理学，可能有助于设计新的干预措施，用于诊断、治疗和监测严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染及其相关的急性和长期后果。
