Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome

Frontiers in Medicine

Medicine

Gustavo Cerda¹  Luciano Ferrada¹  Ute Woehlbier²  Luis A. Quiñones³  Alicia Colombo⁴  Braulio A. Muñoz Ramirez⁵  Valeska Ormazába⁶  Guillermo Nourdin⁷  Elard Koch⁷  Pablo Saldivia⁷  Cristian Vargas⁷  Mauricio A. Hernandez⁷  Carlos Salomon⁸  Maria-Isabel Yuseff⁹  Maria I. Barría^1,10  Erick Riquelme^1,11  Ricardo A. Verdugo^1,12  Jorge Gajardo^1,13  Pamela Garcés^1,13  Jaime J. Lastra^1,13  Rocío Sanhueza^1,14  Felipe A. Zuñiga^1,15  Paula Bustos^1,15  Kevin P. Aguilar^1,15  Mauricio Nazal^1,15  Sergio Sanhueza^1,15  Camilo Cabrera^1,15  Daniela A. Castillo^1,15  Claudio A. Tapia^1,15  Enrique Guzmán-Gutiérrez^1,15  Faryd J. Llerena^1,15  Alexa Moreno^1,15  Romina Quiroga^1,15  Eritson Castro^1,15  Estefania Nova-Lamperti^1,15  Liliana Lamperti^1,15  Bárbara E. Antilef^1,15  Marco Fraga Figueroa^1,15  Paola Lagos^1,15  Mabel A. Vidal^1,16  Gonzalo Labarca^1,17  Mario E. Henriquez-Beltran^1,18  Giovanna Lombardi^1,19  Benilde Riffo^2,20  Jorge Buchert^2,20  David De Gonzalo-Calvo^2,21 

[1] CMA Bío-Bío - Advanced Microscopy Center, University of Concepción, Concepción, Chile;Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile;Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile;Department of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile;Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile;Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile;Servicio de Anatomía Patológica, Hospital Clínico, Universidad de Chile, Santiago, Chile;Department of Pharmacology and Toxicology, School of Medicine, Indiana University Bloomington, Bloomington, IN, United States;Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile;Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile;Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women’s Hospital, Medicine and Biomedical Science Faculty, The University of Queensland, Brisbane, QLD, Australia;Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile;Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile;Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile;Instituto de Investigación Interdisciplinaria y Escuela de Medicina, Universidad de Talca, Talca, Chile;Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile;Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile;Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile;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;Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile;Internal Medicine, Complejo Asistencial Dr. Víctor Ríos Ruiz, Los Ángeles, Chile;Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States;Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile;Núcleo de Investigación en Ciencias de la Salud, Universidad Adventista de Chile, Chillán, Chile;Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile;Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain;Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom;PreveGen Laboratory, Concepción, Chile;Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain;CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain;

关键词: COVID-19;    pulmonary dysfunction;    sequelae;    chemokines;    vascular inflammation;    metabolic syndrome;   

DOI  :  10.3389/fmed.2023.1271863

 received in 2023-08-03, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionLong-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.MethodsPatients 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.ResultsRegarding 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.DiscussionOverall, 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.

【 授权许可】

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Copyright © 2023 Sanhueza, Vidal, Hernandez, Henriquez-Beltran, Cabrera, Quiroga, Antilef, Aguilar, Castillo, Llerena, Fraga Figueroa, Nazal, Castro, Lagos, Moreno, Lastra, Gajardo, Garcés, Riffo, Buchert, Sanhueza, Ormazába, Saldivia, Vargas, Nourdin, Koch, Zuñiga, Lamperti, Bustos, Guzmán-Gutiérrez, Tapia, Ferrada, Cerda, Woehlbier, Riquelme, Yuseff, Muñoz Ramirez, Lombardi, De Gonzalo-Calvo, Salomon, Verdugo, Quiñones, Colombo, Barría, Labarca and Nova-Lamperti.