SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Untargeted Lipidomic Profiling Reveals Lysophosphatidylcholine and Ceramide as Atherosclerotic Risk Factors in <i>apolipoprotein E</i> Knockout Mice

Despite the availability and use of numerous cholesterol-lowering drugs, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality globally. Many researchers have focused their effort on identifying modified lipoproteins. However, lipid moieties such as lysophosphatidylcholine (LPC) and ceramide (CER) contribute to atherogenic events. LPC and CER both cause endothelial mitochondrial dysfunction, leading to fatty acid and triglyceride (TG) accumulation. In addition, they cause immune cells to differentiate into proinflammatory phenotypes. To uncover alternative therapeutic approaches other than cholesterol- and TG-lowering medications, we conducted untargeted lipidomic investigations to assess the alteration of lipid profiles in apolipoprotein E knockout (apoE−/−) mouse model, with or without feeding a high-fat diet (HFD). Results indicated that, in addition to hypercholesterolemia and hyperlipidemia, LPC levels were two to four times higher in apoE−/− mice compared to wild-type mice in C57BL/6 background, regardless of whether they were 8 or 16 weeks old. Sphingomyelin (SM) and CER were elevated three- to five-fold in apoE−/− mice both at the basal level and after 16 weeks when compared to wild-type mice. After HFD treatment, the difference in CER levels elevated more than ten-fold. Considering the atherogenic properties of LPC and CER, they may also contribute to the early onset of atherosclerosis in apoE−/− mice. In summary, the HFD-fed apoE−/− mouse shows elevated LPC and CER contents and is a suitable model for developing LPC- and CER-lowering therapies

Metallic artefact reduction with monoenergetic dual-energy CT: systematic ex vivo evaluation of posterior spinal fusion implants from various vendors and different spine levels

OBJECTIVES: To evaluate optimal monoenergetic dual-energy computed tomography (DECT) settings for artefact reduction of posterior spinal fusion implants of various vendors and spine levels. METHODS: Posterior spinal fusion implants of five vendors for cervical, thoracic and lumbar spine were examined ex vivo with single-energy (SE) CT (120 kVp) and DECT (140/100 kVp). Extrapolated monoenergetic DECT images at 64, 69, 88, 105 keV and individually adjusted monoenergy for optimised image quality (OPTkeV) were generated. Two independent radiologists assessed quantitative and qualitative image parameters for each device and spine level. RESULTS: Inter-reader agreements of quantitative and qualitative parameters were high (ICC = 0.81-1.00, κ = 0.54-0.77). HU values of spinal fusion implants were significantly different among vendors (P < 0.001), spine levels (P < 0.01) and among SECT, monoenergetic DECT of 64, 69, 88, 105 keV and OPTkeV (P < 0.01). Image quality was significantly (P < 0.001) different between datasets and improved with higher monoenergies of DECT compared with SECT (V = 0.58, P < 0.001). Artefacts decreased significantly (V = 0.51, P < 0.001) at higher monoenergies. OPTkeV values ranged from 123-141 keV. OPTkeV according to vendor and spine level are presented herein. CONCLUSIONS: Monoenergetic DECT provides significantly better image quality and less metallic artefacts from implants than SECT. Use of individual keV values for vendor and spine level is recommended. KEY POINTS: • Artefacts pose problems for CT following posterior spinal fusion implants. • CT images are interpreted better with monoenergetic extrapolation using dual-energy (DE) CT. • DECT extrapolation improves image quality and reduces metallic artefacts over SECT. • There were considerable differences in monoenergy values among vendors and spine levels. • Use of individualised monoenergy values is indicated for different metallic hardware devices