Hypoalbuminemia in COVID‐19: assessing the hypothesis for underlying pulmonary capillary leakage

Abstract

Background. Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet.Objective. We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier.Methods. One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied.Results. Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L À1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO 2 -to-FiO 2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. Conclusion.Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.

Prognostic properties of hypoalbuminemia in COVID-19 patients: A systematic review and diagnostic meta-analysis

“…This shiftingeof intravascular fluids to the extravascular space may signify the correlation between albumin level and COVID-19 severity. Additionally, in a hyperinflammatory state, albumin mass will be significantly reduced as a consequence of shorter albumin half-life due to rapid liver and proliferating cells intracellular breakdowns of the albumin [36,43]. Taken together, the more severe the disease, the higher inflammatory reaction robustness yielding to a greater decline in serum albumin level which correlates with poor disease outcome.…”

Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19

“…Another electron microscopy study of vascular damage in COVID-19 lung tissue showed loosened junctional complexes in capillary endothelium, and a role was suggested for albumin leak in pulmonary oedema formation and possibly in hypoalbuminaemia, which is often seen in peripheral blood sampling of critical cases. 43 Notably, Roncati and colleagues 23 observed no viral particles within megakaryocytes to account for their altered behaviour.…”

Clinical–radiological correlations in COVID‐19‐related venous thromboembolism: Preliminary results from a multidisciplinary study

“…We have recently provided insights into the role of increased endothelial permeability in the pathogenesis of COVID-19, of which hypoalbuminemia is one of the useful markers. 11 Therefore, the results presented highlight the complex mechanisms underlying the so-called immunothrombosis which develops in COVID-19, including endothelial damage, abnormal blood flow dynamics, hypercoagulability state, platelet-neutrophil interactions and release of Neutrophil Extracellular Traps or even autoimmune mechanisms. 12 A limitation of our study is that many critically ill patients did not undergo CT angiography because of the marked disproportion between available resources and demand as well as risks related to transport for both patients themselves and healthcare professionals taking care of them during the surge of the epidemic.…”

“…We speculate that the correlation found between Qanadli score and albumin values is not negligible. We have recently provided insights into the role of increased endothelial permeability in the pathogenesis of COVID‐19, of which hypoalbuminemia is one of the useful markers 11 . Therefore, the results presented highlight the complex mechanisms underlying the so‐called immunothrombosis which develops in COVID‐19, including endothelial damage, abnormal blood flow dynamics, hypercoagulability state, platelet–neutrophil interactions and release of Neutrophil Extracellular Traps or even autoimmune mechanisms 12 …”