Risk factors for persistent tomographic abnormalities at 6 months of follow-up in a cohort of hospitalized patients with moderate and severe COVID-19 living at high altitude.

Introduction: After COVID-19, functional and tomographic lung alterations may occur, but there are no studies at high altitude where, due to lower barometric pressure, there are lower levels of arterial oxygen pressure and saturation in both normal subjects and patients with respiratory disease. In this study, we evaluated the computed tomographic (CT), clinical, and functional involvement at 3 and 6 months post-hospitalization in survivors with moderate-severe COVID-19, as well the risk factors associated with abnormal lung computed tomography (ALCT) at 6 months of follow-up. Materials and methods: Prospective cohort, after hospitalization for COVID-19, of patients older than 18 years residing at high altitude. Follow-up at 3 and 6 months with lung CT, spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), six-minute walk test (6MWT), and oxygen saturation (SpO2). Comparisons between ALCT and normal lung computed tomography (NLCT) groups with X2 and Mann-Whitney U test, and paired test for changes between 3 and 6 months. A multivariate analysis was performed to evaluate the variables associated with ALCT at 6-month follow-up. Results: We included 158 patients, 22.2% hospitalized in intensive care unit (ICU), 92.4% with typical COVID CT scan (peripheral, bilateral, or multifocal ground glass, with or without consolidation or findings of organizing pneumonia), and median hospitalization of 7 days. At 6 months, 53 patients (33.5%) had ALCT. There were no differences between ALCT and NLCT groups in symptoms or comorbidities on admission. ALCT patients were older and more frequently men, smokers and hospitalized in ICU. At 3 months, ALCT patients had more frequently a reduced forced vital capacity (< 80%), and lower meters walked (6MWT) and SpO2. At 6 months, all patients improved lung function with no differences between groups, but there were more dyspnea and lower exercise SpO2 in ALCT group. The variables associated with ALCT at 6 months were age, sex, ICU stay, and typical CT scan. Conclusion: At 6-month follow-up, 33.5% of patients with moderate and severe COVID had ALCT. These patients had more dyspnea and lower SpO2 in exercise. Regardless of the persistence of tomographic abnormalities, lung function and 6MWT improved. We identified the variables associated with ALCT.

Chronic Obstructive Pulmonary Disease Patients Have Increased Levels of Plasma Inflammatory Mediators Reported Upregulated in Severe COVID-19.

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators. Methods: Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the "COVID-19 Drug and Gene Set Library" and with experimentally tested protein biomarkers of severe COVID-19. Results: Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19. Conclusions: COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.