HDL proteome remodeling associates with COVID-19 severity.

BACKGROUND: Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases. OBJECTIVE: We used a quantitative proteomic approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19). METHODS: Based on clinical criteria, subjects (n=41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects. RESULTS: We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio [OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval [CI] of 0.07 to 0.72, P=0.007). CONCLUSION: Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases.

Good Cholesterol Gone Bad? HDL and COVID-19.

The transmissible respiratory disease COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide since its first reported outbreak in December of 2019 in Wuhan, China. Since then, multiple studies have shown an inverse correlation between the levels of high-density lipoprotein (HDL) particles and the severity of COVID-19, with low HDL levels being associated with an increased risk of severe outcomes. Some studies revealed that HDL binds to SARS-CoV-2 particles via the virus's spike protein and, under certain conditions, such as low HDL particle concentrations, it facilitates SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) and infection of host cells. Other studies, however, reported that HDL suppressed SARS-CoV-2 infection. In both cases, the ability of HDL to enhance or suppress virus infection appears to be dependent on the expression of the HDL receptor, namely, the Scavenger Receptor Class B type 1 (SR-B1), in the target cells. SR-B1 and HDL represent crucial mediators of cholesterol metabolism. Herein, we review the complex role of HDL and SR-B1 in SARS-CoV-2-induced disease. We also review recent advances in our understanding of HDL structure, properties, and function during SARS-CoV-2 infection and the resulting COVID-19 disease.

COVID-19 induces proatherogenic alterations in moderate to severe non-comorbid patients: A single-center observational study.

Patients with COVID-19 can be asymptomatic or present mild to severe symptoms, leading to respiratory and cardiovascular complications and death. Type 2 diabetes mellitus (T2DM) and obesity are considered risk factors for COVID-19 poor prognosis. In parallel, COVID-19 severe patients exhibit dyslipidemia and alterations in neutrophil to lymphocyte ratio (NLR) associated with disease severity and mortality. To investigate whether such alterations are caused by the infection or results from preexisting comorbidities, this work analyzed dyslipidemia and the hemogram profile of COVID-19 patients according to the severity and compared with patients without T2DM or obesity comorbidities. Dyslipidemia, with a marked decrease in HDL levels, and increased NLR accompanied the disease severity, even in non-T2DM and non-obese patients, indicating that COVID-19 causes the observed alterations. Because decreased hemoglobin is involved in COVID-19 severity, and hemoglobin concentration is associated with metabolic diseases, the erythrogram of patients was also evaluated. We verified a drop in hemoglobin and erythrocyte number in severe patients, independently of T2DM and obesity, which may explain in part the need for artificial ventilation in severe cases. Thus, the control of such parameters (especially HDL levels, NLR, and hemoglobin concentration) could be a good strategy to prevent COVID-19 complications and death.

The clinical value of high-density lipoprotein in the evaluation of new coronavirus pneumonia.

BACKGROUND: The new coronavirus pneumonia (NCP, COVID-19) outbreak began in Wuhan in December 2019. The new coronavirus (2019 novel coronavirus (2019-nCoV)) can cause multiple organ damage, mainly to lung tissue, and induce inflammation in the body. OBJECTIVES: To investigate the changes of high-density lipoprotein (HDL) level in patients with COVID-19 and assess its value in the evaluation and prognosis of this disease. MATERIAL AND METHODS: This paper is a cross-sectional retrospective study. Eighty-six severe COVID-19 patients, 132 non-severe COVID-19 patients and 76 healthy individuals (control group) were recruited to measure triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using enzyme-coupled colorimetry. RESULTS: The serum HDL-C level in COVID-19 group was 1.02 ±0.28 mmol/L which was significantly lower than in control group (1.52 ±0.55 mmol/L) (p < 0.05). In addition, the serum HDL-C level in severe COVID-19 group was 0.83 ±1.67 mmol/L, which was significantly lower than that in non-severe COVID-19 group (1.15 ±0.27 mmol/L) (p < 0.05). CONCLUSIONS: Changes in HDL levels in patients with COVID-19 can reflect the severity of the disease and have a clinical significance in establishing the prognosis.

Altered high-density lipoprotein composition and functions during severe COVID-19.

Coronavirus disease 2019 (COVID-19) pandemic is affecting millions of patients worldwide. The consequences of initial exposure to SARS-CoV-2 go beyond pulmonary damage, with a particular impact on lipid metabolism. Decreased levels in HDL-C were reported in COVID-19 patients. Since HDL particles display antioxidant, anti-inflammatory and potential anti-infectious properties, we aimed at characterizing HDL proteome and functionality during COVID-19 relative to healthy subjects. HDLs were isolated from plasma of 8 severe COVID-19 patients sampled at admission to intensive care unit (Day 1, D1) at D3 and D7, and from 16 sex- and age-matched healthy subjects. Proteomic analysis was performed by LC-MS/MS. The relative amounts of proteins identified in HDLs were compared between COVID-19 and controls. apolipoprotein A-I and paraoxonase 1 were confirmed by Western-blot analysis to be less abundant in COVID-19 versus controls, whereas serum amyloid A and alpha-1 antitrypsin were higher. HDLs from patients were less protective in endothelial cells stiumalted by TNFα (permeability, VE-cadherin disorganization and apoptosis). In these conditions, HDL inhibition of apoptosis was blunted in COVID-19 relative to controls. In conclusion, we show major changes in HDL proteome and decreased functionality in severe COVID-19 patients.