Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications

Abstract

High-density lipoproteins (HDLs) are a class of blood particles, principally involved in mediating reverse cholesterol transport from peripheral tissue to liver. Omics approaches have identified crucial mediators in the HDL proteomic and lipidomic profile, which are involved in distinct pleiotropic functions. Besides their role as cholesterol transporter, HDLs display anti-inflammatory, anti-apoptotic, anti-thrombotic, and anti-infection properties. Experimental and clinical studies have unveiled significant changes in both HDL serum amount and composition that lead to dysregulated host immune response and endothelial dysfunction in the course of sepsis. Most SARS-Coronavirus-2-infected patients admitted to the intensive care unit showed common features of sepsis disease, such as the overwhelmed systemic inflammatory response and the alterations in serum lipid profile. Despite relevant advances, episodes of mild to moderate acute kidney injury (AKI), occurring during systemic inflammatory diseases, are associated with long-term complications, and high risk of mortality. The multi-faceted relationship of kidney dysfunction with dyslipidemia and inflammation encourages to deepen the clarification of the mechanisms connecting these elements. This review analyzes the multifaced roles of HDL in inflammatory diseases, the renal involvement in lipid metabolism, and the novel potential HDL-based therapies.

Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

“…The RBD of the SARS-CoV-2 S protein has a particular affinity for cholesterol and HDL components, enhancing the virus entry into the cell through SR-B1, suggesting that this interaction is dependent on the presence of membrane cholesterol (Figure 1) (12). In addition, ACE-2 and SRB-1 are co-expressed in multiple susceptible tissues (159). Therefore, this evidence further supports the important role of cholesterol-rich lipid rafts and receptors that regulate lipid entry into the cell to enhance the SARS-CoV-2 entry.…”

Persistence of Lipoproteins and Cholesterol Alterations after Sepsis: Implication for Atherosclerosis Progression

“…HDL-c also binds to lipoteichoic acid (LTA), affecting inflammatory responses mediated through TLR2 [140]. HDL-c also plays an important role in modulating viral responses via separate mechanisms, but the clinical mechanism is pathogen-dependent [141]. HDL-c can facilitate cellular entry of hepatitis C, Dengue, or SARS-CoV-2 virus [142][143][144].…”

COVID‐19 vulnerabilities are intensified by declining human serum albumin levels

“…3. Hypoalbuminaemia is also a known factor in sepsis, acute respiratory distress syndrome (ARDS) and COVID (Roger, 2021;Stasi et al, 2021).…”

“…COVID‐19 complications occur at the systemic stage of the infection and then lead to the integral collapse of the endothelial cellular structure leading to the more serious systemic symptoms and death. We propose that this is caused by a similar system to that of sepsis (Johnson et al., 2020; Roger, 2021; Stasi et al., 2021), but which we have redefined more specifically for operational purposes as being ‘the symptoms caused by an inoperative systemic nutrient transport system’. We provide evidence that the main cause of this is insufficient unbound HSA.…”