COVID-19: the key role of pulmonary capillary leakage. An observational cohort study

BackgroundCOVID-19 induces progressive hypoxemic respiratory failure and acute respiratory distress syndrome, mostly due to a dysregulated inflammatory response. Since the first observations of COVID-19 patients, significant hypoalbuminemia was detected. This study aimed to investigate the hypothesis that hypoalbuminemia in COVID-19 patients is due to pulmonary capillary leakage and to test its correlation with indicators of respiratory function. Methods174 COVID-19 patients, 92 admitted to the Intermediate Medicine ward (IMW), and 82 to the Intensive Care Unit (ICU) at Luigi Sacco Hospital in Milan were included in this study. FindingsSerum albumin concentration was decreased in the whole cohort, with ICU patients displaying lower values than IMW patients [20 (18-23) vs 28 (24-33) g{middle dot}|-1, p<0.001], Lower albumin values were found in patients belonging to a more compromised group (lower PaO2 to FiO2 ratio and worst chest X-ray findings). In a subset of 26 patients, analysis of bronchoalveolar lavage fluid (BALF) highlighted high protein concentrations, which were correlated to Interleukin-8 and Interleukin-10 BALF concentration. The length of hospitalisation [20 (15-29) vs 8 (5-14) days, p<0.0001] and death rate (52.4% vs 21.7%, p<0.0001) were higher in ICU than in IMW patients, while a strict relation between hypoalbuminemia and 30 day-survival was detected in the whole cohort. Electron microscopy examinations of eight out of ten autopsy lung tissues showed diffuse loosening of interendothelial junctional complex. InterpretationThe degree of hypoalbuminemia can be considered as a useful severity marker in hospitalised COVID-19 patients. Pulmonary capillary leak syndrome secondary to the hyperinflammatory state plays a key role in the pathogenesis of COVID-19 respiratory dysfunction and should be regarded as a therapeutic target.