Cardiac dysfunction mediators CXCL-9 and chemotaxis of phagocytes characterized patients with long-term pulmonary dysfunction after COVID-19.

Abstract

Abstract Severe COVID-19 is characterized by marked cytokine release and pulmonary dysfunction; however, it is still unknown which mediators support post-COVID-19 pulmonary dysfunction. Our aim was to determine the signaling pathways associated with long-term pulmonary dysfunction in patients with COVID-19. Our cohort of 60 patients with COVID-19 were followed up at 4- and 12-months post infection. Pulmonary sequelae were analyzed by computed tomography (CT), diffusing capacity of carbon monoxide (DLCO), spirometry, 6-minute walk test (6MWT) and handgrip test. Cytokines, chemokines and blood tests parameters were also analyzed. Furthermore, signaling pathways associated with pulmonary dysfunction were identified by serum proteomics analysis using TimsTOF-Pro and ingenuity pathway analysis. Fourteen patients with CT and abnormal DLCO were classified as patients with long-term pulmonary dysfunction (LTPD), who also presented impaired spirometry tests, 6MWT and handgrip strength than patients without sequelae or patients with CT only. We observed that only CXCL-9 was significantly increased in LTPD patients in comparison with other groups. In addition, the main signaling pathways identified by proteomics in LTPD patients were associated with an immunothrombotic state related to cardiac dysfunction, migration of dysfunctional monocytes and reduced IFN-signaling. In summary, patients with LTPD presented a restrictive lung condition, with greater fatigue, lower aerobic capacity and muscle strength 4-months post-COVID-19. Our data suggest that patients with previous cardiac dysfunction who had severe o moderate COVID-19 are more susceptible to develop LTPD. PROYECTO COVID1005, ACT210085 y Fondecyt Regular 1211480.