Research makes important discovery about pulmonary sequelae after COVID-19 infection

A collaborative study led by Dr. Estefanía Nova-Lamperti of the Universidad de Concepción, Dr. Gonzalo Labarca of Harvard University, and Mauricio Hernández, of MELISA Institute, and which included the participation of researchers from leading academic institutions, sought to identify the sequelae associated with long-term pulmonary dysfunction (L-PDD) in patients with COVID-19. The study was published in Frontiers in Medicine.

During the COVID-19 pandemic, various types of sequelae have been identified in sustained patients recovered from SARS-CoV-2. To refer to this phenomenon, researchers have used the terminology of post-acute COVID-19, post-COVID-19 syndrome or long COVID-19. Likewise, to be classified as such, the symptoms must not be attributable to other causes.

Among the symptoms identified, several pulmonary manifestations have been reported. For example, alteration in computed tomography (CT) scan after infection has been associated with the need for invasive mechanical ventilation during the acute phase of the disease, while a reduction in carbon monoxide diffusion capacity (DLCO) is one of the most reported lung function disturbances 6 months after COVID-19. Similarly, severe acute COVID-19 has been associated with an increased risk of long-term pulmonary sequelae, including pulmonary structural abnormalities and impaired O2 diffusion.

Based on this, Dr. Estefanía Nova-Lamperti, explained that "the objective of our study was to identify post-COVID-19 pulmonary sequelae, in the short and medium term, in a cohort of Chilean patients prior to the appearance of vaccines on the market, and to determine the inflammatory pathways at the cellular and molecular level, associated with sustained lung failure over time."

The cohort of this study consisted of 60 subjects who had COVID-19 (mild, moderate, or severe), who were evaluated according to the results of their CT scan and DLCOc examination at 4 months after infection, to identify patients with long-term pulmonary dysfunction (L-TPD).

Subsequently, once L-TPD was confirmed, the main parameters supporting this condition were identified during the acute phase of the pathology and 4 months after infection, in addition to the concomitant long-term consequences at 12 months after COVID-19 infection.

Regarding the methodology of the research, Dr. Gonzalo Labarca indicated that a prospective translational clinical study was carried out in a rather complex time, such as the beginning of the pandemic. "The focus of the study was to look at the sequelae between the third and fourth month, and after one year after the acute infection. We focused on clinical characteristics such as comorbidities, mental health, physical health, fatigue, cardiopulmonary functions and an in-depth study of sleep (considering a priori that these systems were going to be significantly altered). Curiously, this was the case, and both for the first evaluation and the one that was done after a year, we found a high percentage of symptoms, in addition to metabolic dysfunction, insulin insufficiency and diabetes that occurred over time, which gave us light on what the sequelae of COVID were in the clinical aspect," he added.

For Mauricio Hernández, Chief Laboratory Officer of MELISA Institute, proteomics was a fundamental tool in carrying out this research: "In our laboratory we have developed a robust methodology for the massive analysis of serum and plasma, which undoubtedly positions us as one of the research centers with the greatest capacity in Latin America. Thanks to this, we were able to obtain valuable information that allowed us to describe, from an immunological and systemic point of view, how the patients evolved over time, which was consistent with the data obtained clinically."

This research concluded that long-term pulmonary dysfunction is associated with advanced age, acute respiratory distress, and the presence of hypertension and insulin resistance. Regarding these findings, Dr. Nova-Lamperti pointed out that "we realized that patients who maintain lung damage presented a hypoxic state, even up to 12 months after infection, greater systemic inflammation that affected the endothelial barrier, reduction in the phagocytosis response mediated by Fc receptors and increase in metabolic syndrome and insulin-resistance. That is why individuals with LONG-COVID should have a treatment defined by multidisciplinary teams that seek the gradual recovery of the patient through physical exercise, mental health therapy and nutritional intervention."

Finally, Dr. Elard Koch, senior researcher and Chairman of MELISA Institute, said that they were pleased with the publication of this study and stressed the importance of the participation of researchers from the staff of the MELISA Institute in research of this type: "for us it is really gratifying when researchers from our research and biotechnology center participate in research as relevant as this, which is certainly an important goal for our institution," Koch remarked.

###

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the Agencia Nacional de Investigación y Desarrollo (ANID) ANID/COVID1005 and ANID/ACT210085), Chilean Government. GL declares funding for research by the American Academy of Sleep Medicine (AASM, 254-FP-21). ENL, SS, CC, RQ, and BA were funded by Fondecyt Regular 1211480 and COVID-19 Genomics Network (C19-GenoNet) ANID/ACT210085. Flow Cytometer was funded by EQM150061 (FONDEQUIP-ANID). UW was funded by Fondecyt Regular 1200459. DG-C has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041) co-funded by the European Union. CIBERES (CB07/06/2008) is an initiative of the Instituto de Salud Carlos III. MB and EN-L are funded by ANID/ATE220034. MH was supported by CLA-023023-2 FISAR.

Participating researchers:

Sergio Sanhueza (1), Mabel A. Vidal (1, 2), Mauricio A. Hernandez (3), Mario E. Henriquez-Beltran (1, 4, 5, 6), Camilo Cabrera (1), Romina Quiroga (1), Bárbara E. Antilef (1), Kevin P. Aguilar (1), Daniela A. Castillo (1), Faryd J. Llerena (1), Marco Fraga Figueroa (1), Mauricio Nazal (1), Eritson Castro (1), Paola Lagos (1), Alexa Moreno (1), Jaime J. Lastra (7), Jorge Gajardo (7), Pamela Garcés (7), Benilde Riffo (8), Jorge Buchert (8), Rocío Sanhueza (5), Valeska Ormazába (9), Pablo Saldivia (3), Cristian Vargas (3), Guillermo Nourdin (3), Elard Koch (3), Felipe A Zuñiga (1), Liliana Lamperti (1), Paula Bustos (1), Enrique Guzmán-Gutiérrez (1), Claudio A Tapia (1), Luciano Ferrada (10), Gustavo Cerda (10), Ute Woehlbier (11), Erick Riquelme (12), Maria-Isabel Yuseff (13), Braulio A Muñoz Ramirez (14), Giovanna Lombardi (15), David De Gonzalo-Calvo (6, 16), Carlos Salomon (17), Ricardo A Verdugo (18), Luis A Quiñones (19, 20, 21), Alicia Colombo (19, 22), Maria I Barría (23), Gonzalo Labarca (1, 24, 25), Estefania Nova-Lamperti (1).

Affiliations:

(1) Molecular and Translational Immunology Laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepción, Concepción, Chile; (2) Facultad de Ingeniería, Diseño y Arquitectura, Universidad San Sebastián, Concepción, Chile; (3) Division of Biotechnology, MELISA Institute, San Pedro de la Paz, Chile; (4) Núcleo de Investigación en Ciencias de la Salud, Universidad Adventista de Chile, Chillán, Chile; (5) Kinesiology School, Escuela de Kinesiología, Facultad de Salud, Universidad Santo Tomás, Los Ángeles, Chile; (6) Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain; (7) Internal Medicine Department, Hospital Guillermo Grant Benavente and Medicine Faculty, University of Concepción, Concepción, Chile; (8) PreveGen Laboratory, Concepción, Chile; (9) Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile; (10) CMA Bío-Bío - Advanced Microscopy Center, University of Concepción, Concepción, Chile; (11) Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile; (12) Faculty of Medicine, Pontifical Catholic University of Chile, Santiago, Chile; (13) Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; (14) Department of Pharmacology and Toxicology, School of Medicine, Indiana University Bloomington, Bloomington, IN, United States; (15) Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; (16) CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain; (17) 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; (18) Instituto de Investigación Interdisciplinaria y Escuela de Medicina, Universidad de Talca, Talca, Chile; (19) Department of Basic-Clinical Oncology, Faculty of Medicine, University of Chile, Santiago, Chile; (20) Department of Pharmaceutical Sciences and Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile; (21) Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Santiago, Chile; (22) Servicio de Anatomía Patológica, Hospital Clínico, Universidad de Chile, Santiago, Chile; (23) Facultad de Medicina y Ciencia, Universidad San Sebastián, Puerto Montt, Chile; (24) Internal Medicine, Complejo Asistencial Dr. Víctor Ríos Ruiz, Los Ángeles, Chile; (25) Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.