Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

The recently emerged pathogenic SARS-coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global pandemic. In this study, we show that SARS-CoV-2 infection was associated with clinically significant lower level of HDL cholesterol (HDL-C), which can be used as indicators of disease severity and poor prognosis. Importantly, we found the spike protein of SARS-CoV-2 (SARS-2-S) bound to HDL. Antagonists of HDL receptor-Scavenger receptor class B type I (SR-B1), strongly inhibited SARS-CoV-2 infection. Notably, the lipids transfer function of SR-B1 was indispensable for this inhibition, offering explanations for the reduced serum HDL level observed in COVID-19 patients. Basing on findings here, we speculate that SR-B1-mediated pulmonary HDL-vitamin E uptake could participate in mediating SARS-CoV-2 infection of lung cells, and the unique expression profile of SR-B1 may also affect SARS-CoV-2 cell and tissue tropism. These findings might help to provide further insights into viral transmission, pathological characteristics and reveal therapeutic targets.

Abstract. The aim of this study was to evaluate the prognostic effect of test parameters from pretreatment complete blood count (CBC) for predicting outcome in breast cancer patients. A total of 162 patients with breast cancer and a long follow-up were enrolled in this study. Red cell indices (RCIs) and neutrophil-lymphocyte ratio (NLR) from CBC prior to treatment, as well as related clinical data, were retrospectively collected. We evaluated the association of RCI and NLR with tumor size, clinical stage, histological grade, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We further performed survival analysis and Cox multivariate analysis, stratified by RCI and NLR median values, to evaluate their prognostic effects. In the disease-free survival (DFS) analysis, patients in the higher mean corpuscular hemoglobin (MCH) and NLR groups exhibited shorter DFS times compared with those in the lower MCH and NLR groups (P=0.017 for MCH and P=0.039 for NLR). The univariate analysis revealed that both MCH and NLR were significantly associated with DFS. The Cox multivariate analysis demonstrated that only MCH was an independent predictor associated with disease relapse (hazard ratio = 1.975, 95% confidence interval: 1.118-3.487, P=0.019), whereas no index was associated with overall survival. Our results suggest that MCH prior to treatment may be a predictive marker associated with DFS in breast cancer.

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Objective The present study investigated the effects of a bolus intracoronary injection of nicorandil on systemic inflammation and oxidative stress induced by percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD). Methods Patients undergoing coronary angiography (CAG) were enrolled into the CAG group (n = 30). Patients undergoing PCI were randomly divided into the PCI (n = 30) and PCI + nicorandil groups (n = 30). Results Blood taken from patients in the placebo group 24 hours after PCI exhibited significant increases in the expression of inflammatory indicators and mild increases in the expression of anti-inflammatory indicators. The intracoronary injection of nicorandil reversed the elevation of inflammatory indicators and significantly increased the levels of anti-inflammatory indicators in the blood of patients with PCI. Blood taken from patients in the placebo group 24 hours after PCI also displayed significant decreased superoxide dismutase levels and increased malondialdehyde levels. Nicorandil treatment reversed these changes of oxidative stress marker levels. Conclusions These results indicated the possible medical application of intracoronary injections of nicorandil for reducing systemic inflammation and oxidative stress in the peripheral blood of patients undergoing PCI.