Asociación de citoquinas con secuelas funcionales del pulmón en pacientes recuperados de COVID-19.
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Date
2021
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Publisher
Universidad de Concepción
Abstract
El síndrome respiratorio agudo severo corovavirus-2 (SARS-CoV-2) es el agente etiológico de la enfermedad por Coronavirus 2019 (COVID-19). La patología puede desarrollarse con distinta severidad entre los pacientes, desde una etapa leve, moderada a severa, siendo característico entre los enfermos críticos una marcada liberación de proteínas inflamatorias y el desarrollo del síndrome respiratorio agudo severo (SARS), el cual sigue siendo hasta el día de hoy la principal complicación médica en los infectados. Con el paso del tiempo la COVID-19 severa se ha asociado con secuelas pulmonares sostenidas después de la fase aguda, sin embargo, los mediadores inflamatorios asociados con la disfunción pulmonar tras superar la COVID-19 siguen siendo desconocidos. El objetivo de este estudio fue identificar citoquinas y quimioquinas asociadas con disfunción pulmonar 6 y 12 meses post-COVID-19 en pacientes con enfermedad leve, moderada y severa. Para aquello se reclutaron 60 pacientes COVID-19 del Hospital Víctor-Rios-Ruiz, 6 y 12 meses después de la fase aguda, obteniendo en estos periodos de tiempo muestras de suero para determinar 6 citoquinas y 4 quimioquinas. La cuantificación de las proteínas se realizó utilizando un ensayo de array por citometria de flujo. Las secuelas respiratorias de los pacientes post COVID-19 se analizaron midiendo el daño estructural del pulmón a través de tomografías computarizadas de tórax (TCT), además de analizar las secuelas funcionales del pulmón a través de los exámenes de espirometría y difusión de monóxido de carbono pulmonar (DLCO). Nuestros datos mostraron que 22 pacientes presentaban deterioro de la función pulmonar 6 meses después de la infección por COVID-19. Luego de identificar a los pacientes con secuelas pulmonares, observamos que CXCL-9, CXCL10 e IL 6 fueron los principales mediadores inflamatorios asociados con la disfunción pulmonar a los 6 meses. Finalmente, del grupo de pacientes con secuelas funcionales a nivel pulmonar a los 6 meses, comparamos la presencia de citoquinas entre los pacientes que recuperaron la función pulmonar a los 12 meses y los pacientes que mantuvieron disfunción pulmonar, observando que los niveles de CXCL-9, CXCL10 e IL-6 a los 6 meses aumentaron en el grupo de pacientes que mantuvieron la disfunción pulmonar 12 meses después del COVID-19. De esta forma es que los niveles elevados de CXCL-9, CXCL-10 e IL 6 se asocian con secuelas en la funcionalidad pulmonar a largo plazo después de COVID-19. Volviéndose interesante estudiar, en investigaciones a futuro, el mecanismo patológico por el cual estas proteínas inflamatorias logran contribuir a la disfunción pulmonar en los pacientes que superan la patología.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent of Coronavirus disease 2019 (COVID-19). The pathology can develop with different severity among patients, from a mild, moderate to severe stage, being characteristic among critically ill patients a marked release of inflammatory proteins and the development of severe acute respiratory syndrome (SARS), which remains to this day the main medical complication in those infected. Over time, severe COVID-19 has been associated with sustained lung sequelae after the acute phase, however, the inflammatory mediators associated with lung dysfunction after overcoming COVID-19 remain unknown. The objective of this study was to identify cytokines and chemokines associated with pulmonary dysfunction 6 and 12 months post-COVID-19 in patients with mild, moderate and severe disease. For this, 60 COVID-19 patients were recruited from the Víctor Rios-Ruiz Hospital, 6 and 12 months after the acute phase, obtaining serum samples in these periods of time to determine 6 cytokines and 4 chemokines. Protein quantification was performed using a flow cytometric array assay. The respiratory sequelae of post-COVID-19 patients were analyzed by measuring the structural damage of the lung through computed tomography of the chest (CTT), in addition to analyzing the functional sequelae of the lung through spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Our data showed that 22 patients had impaired lung function 6 months after COVID-19 infection. After identifying the patients with pulmonary sequelae, we observed that CXCL-9, CXCL10 and IL-6 were the main inflammatory mediators associated with pulmonary dysfunction at 6 months. Finally, from the group of patients with functional sequelae at the lung level at 6 months, we compared the presence of cytokines between the patients who recovered lung function at 12 months and the patients who maintained lung dysfunction, observing that the levels of CXCL-9, CXCL-10 and IL-6 at 6 months increased in the group of patients who maintained pulmonary dysfunction 12 months after COVID-19. Thus, elevated levels of CXCL-9, CXCL-10, and IL-6 are associated with long-term sequelae in lung function after COVID-19. It is becoming interesting to study, in future research, the pathological mechanism by which these inflammatory proteins contribute to pulmonary dysfunction in patients who overcome the pathology.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the etiological agent of Coronavirus disease 2019 (COVID-19). The pathology can develop with different severity among patients, from a mild, moderate to severe stage, being characteristic among critically ill patients a marked release of inflammatory proteins and the development of severe acute respiratory syndrome (SARS), which remains to this day the main medical complication in those infected. Over time, severe COVID-19 has been associated with sustained lung sequelae after the acute phase, however, the inflammatory mediators associated with lung dysfunction after overcoming COVID-19 remain unknown. The objective of this study was to identify cytokines and chemokines associated with pulmonary dysfunction 6 and 12 months post-COVID-19 in patients with mild, moderate and severe disease. For this, 60 COVID-19 patients were recruited from the Víctor Rios-Ruiz Hospital, 6 and 12 months after the acute phase, obtaining serum samples in these periods of time to determine 6 cytokines and 4 chemokines. Protein quantification was performed using a flow cytometric array assay. The respiratory sequelae of post-COVID-19 patients were analyzed by measuring the structural damage of the lung through computed tomography of the chest (CTT), in addition to analyzing the functional sequelae of the lung through spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO). Our data showed that 22 patients had impaired lung function 6 months after COVID-19 infection. After identifying the patients with pulmonary sequelae, we observed that CXCL-9, CXCL10 and IL-6 were the main inflammatory mediators associated with pulmonary dysfunction at 6 months. Finally, from the group of patients with functional sequelae at the lung level at 6 months, we compared the presence of cytokines between the patients who recovered lung function at 12 months and the patients who maintained lung dysfunction, observing that the levels of CXCL-9, CXCL-10 and IL-6 at 6 months increased in the group of patients who maintained pulmonary dysfunction 12 months after COVID-19. Thus, elevated levels of CXCL-9, CXCL-10, and IL-6 are associated with long-term sequelae in lung function after COVID-19. It is becoming interesting to study, in future research, the pathological mechanism by which these inflammatory proteins contribute to pulmonary dysfunction in patients who overcome the pathology.
Description
Tesis presentada para optar al título de Bioquímico/a.
Keywords
Citoquinas, COVID-19 (enfermedad), Virus del SARS, Antígenos de histocompatibilidad