Sanhueza Sergio, Vidal Mabel A, Hernandez Mauricio A, Henriquez-Beltran Mario E, Cabrera Camilo, Quiroga Romina, Antilef Bárbara E, Aguilar Kevin P, Castillo Daniela A, Llerena Faryd J, Fraga Figueroa Marco, Nazal Mauricio, Castro Eritson, Lagos Paola, Moreno Alexa, Lastra Jaime J, Gajardo Jorge, Garcés Pamela, Riffo Benilde, Buchert Jorge, Sanhueza Rocío, Ormazába Valeska, Saldivia Pablo, Vargas Cristian, Nourdin Guillermo, Koch Elard, Zuñiga Felipe A, Lamperti Liliana, Bustos Paula, Guzmán-Gutiérrez Enrique, Tapia Claudio A, Ferrada Luciano, Cerda Gustavo, Woehlbier Ute, Riquelme Erick, Yuseff Maria-Isabel, Muñoz Ramirez Braulio A, Lombardi Giovanna, De Gonzalo-Calvo David, Salomon Carlos, Verdugo Ricardo A, Quiñones Luis A, Colombo Alicia, Barría Maria I, Labarca Gonzalo, Nova-Lamperti Estefania
Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile.
Facultad de Ingeniería, Diseño y Arquitectura, Universidad San Sebastián, Concepción, Chile.
Front Med (Lausanne). 2023 Oct 6;10:1271863. doi: 10.3389/fmed.2023.1271863. eCollection 2023.
Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling.
Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection.
Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups.
Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.
长期肺部功能障碍（L-TPD）是长期新冠的最关键表现之一。这种肺部病变与急性期疾病严重程度及既往合并症有关，然而，其临床表现、伴随后果以及支持这种临床状况的分子途径仍不清楚。本研究的目的是通过分析机器学习和血清蛋白质组分析支持的临床参数和功能测试，识别并表征长期新冠患者的L-TPD，并阐明归因于这种状况的主要途径和长期后果。
根据感染后4个月和12个月时的计算机断层扫描（CT）结果以及根据血红蛋白校正的肺一氧化碳弥散量（DLCOc）测试结果，对L-TPD患者进行分类。
关于急性期，我们的数据显示，计算机蛋白质组学表明，L-TPD在患有高血压或胰岛素抵抗的老年患者中更为常见，这与血管炎症和吞噬细胞趋化性相关途径有关。然后，在感染后4个月，临床和功能测试显示，L-TPD患者表现出限制性肺病、有氧运动能力受损和肌肉力量下降。此时，在L-TPD患者中观察到血小板和CXCL9循环水平升高，以及由于CD14+单核细胞中FcγRIII（CD16）表达降低导致Fcγ受体介导的吞噬作用受到抑制。最后，在感染1年后，与其他患者组相比，L-TPD患者的代谢综合征恶化，体重指数增加。
总体而言，我们的数据表明，CT扫描和DLCOc可识别新冠后患有L-TPD的患者。这种状况与血管炎症以及FcγRIII表达降低导致病毒-抗体免疫复合物的吞噬作用受损有关。此外，我们得出结论，新冠幸存者需要个性化随访和适当干预，以减少长期后遗症和进一步代谢疾病的出现。
