Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome
Authors: 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 
Published: October 2023

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.