Frontiers in Medicine (Oct 2023)
Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome
- Sergio Sanhueza,
- Mabel A. Vidal,
- Mabel A. Vidal,
- Mauricio A. Hernandez,
- Mario E. Henriquez-Beltran,
- Mario E. Henriquez-Beltran,
- Mario E. Henriquez-Beltran,
- Mario E. Henriquez-Beltran,
- Camilo Cabrera,
- Romina Quiroga,
- Bárbara E. Antilef,
- Kevin P. Aguilar,
- Daniela A. Castillo,
- Faryd J. Llerena,
- Marco Fraga Figueroa,
- Mauricio Nazal,
- Eritson Castro,
- Paola Lagos,
- Alexa Moreno,
- Jaime J. Lastra,
- Jorge Gajardo,
- Pamela Garcés,
- Benilde Riffo,
- Jorge Buchert,
- Rocío Sanhueza,
- Valeska Ormazába,
- Pablo Saldivia,
- Cristian Vargas,
- Guillermo Nourdin,
- Elard Koch,
- Felipe A. Zuñiga,
- Liliana Lamperti,
- Paula Bustos,
- Enrique Guzmán-Gutiérrez,
- Claudio A. Tapia,
- Luciano Ferrada,
- Gustavo Cerda,
- Ute Woehlbier,
- Erick Riquelme,
- Maria-Isabel Yuseff,
- Braulio A. Muñoz Ramirez,
- Giovanna Lombardi,
- David De Gonzalo-Calvo,
- David De Gonzalo-Calvo,
- Carlos Salomon,
- Ricardo A. Verdugo,
- Luis A. Quiñones,
- Luis A. Quiñones,
- Luis A. Quiñones,
- Alicia Colombo,
- Alicia Colombo,
- Maria I. Barría,
- Gonzalo Labarca,
- Gonzalo Labarca,
- Gonzalo Labarca,
- Estefania Nova-Lamperti
Affiliations
- Sergio Sanhueza
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Mabel A. Vidal
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Mabel A. Vidal
- Facultad de Ingeniería, Diseño y Arquitectura, Universidad San Sebastián, Concepción, Chile
- Mauricio A. Hernandez
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
- Mario E. Henriquez-Beltran
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Mario E. Henriquez-Beltran
- Núcleo de Investigación en Ciencias de la Salud, Universidad Adventista de Chile, Chillán, Chile
- Mario E. Henriquez-Beltran
- Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile
- Mario E. Henriquez-Beltran
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
- Camilo Cabrera
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Romina Quiroga
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Bárbara E. Antilef
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Kevin P. Aguilar
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Daniela A. Castillo
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Faryd J. Llerena
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Marco Fraga Figueroa
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Mauricio Nazal
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Eritson Castro
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Paola Lagos
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Alexa Moreno
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Jaime J. Lastra
- Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile
- Jorge Gajardo
- Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile
- Pamela Garcés
- Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile
- Benilde Riffo
- PreveGen Laboratory, Concepción, Chile
- Jorge Buchert
- PreveGen Laboratory, Concepción, Chile
- Rocío Sanhueza
- Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile
- Valeska Ormazába
- Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile
- Pablo Saldivia
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
- Cristian Vargas
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
- Guillermo Nourdin
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
- Elard Koch
- Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile
- Felipe A. Zuñiga
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Liliana Lamperti
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Paula Bustos
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Enrique Guzmán-Gutiérrez
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Claudio A. Tapia
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Luciano Ferrada
- 0CMA Bío-Bío - Advanced Microscopy Center, University of Concepción, Concepción, Chile
- Gustavo Cerda
- 0CMA Bío-Bío - Advanced Microscopy Center, University of Concepción, Concepción, Chile
- Ute Woehlbier
- 1Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile
- Erick Riquelme
- 2Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
- Maria-Isabel Yuseff
- 3Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
- Braulio A. Muñoz Ramirez
- 4Department of Pharmacology and Toxicology, School of Medicine, Indiana University Bloomington, Bloomington, IN, United States
- Giovanna Lombardi
- 5Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
- David De Gonzalo-Calvo
- Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain
- David De Gonzalo-Calvo
- 6CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
- Carlos Salomon
- 7Exosome 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
- Ricardo A. Verdugo
- 8Instituto de Investigación Interdisciplinaria y Escuela de Medicina, Universidad de Talca, Talca, Chile
- Luis A. Quiñones
- 9Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile
- Luis A. Quiñones
- 0Department of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile
- Luis A. Quiñones
- 1Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile
- Alicia Colombo
- 9Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile
- Alicia Colombo
- 2Servicio de Anatomía Patológica, Hospital Clínico, Universidad de Chile, Santiago, Chile
- Maria I. Barría
- 3Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile
- Gonzalo Labarca
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- Gonzalo Labarca
- 4Internal Medicine, Complejo Asistencial Dr. Víctor Ríos Ruiz, Los Ángeles, Chile
- Gonzalo Labarca
- 5Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Estefania Nova-Lamperti
- Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile
- DOI
- https://doi.org/10.3389/fmed.2023.1271863
- Journal volume & issue
-
Vol. 10
Abstract
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.
Keywords