OBJECTIVE: To study the neurological manifestations of patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective case series SETTING: Three designated COVID-19 care hospitals of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China. PARTICIPANTS: Two hundred fourteen hospitalized patients with laboratory confirmed diagnosis of severe acute respiratory syndrome from coronavirus 2 (SARS-CoV-2) infection. Data were collected from 16 January 2020 to 19 February 2020. MAIN OUTCOME MEASURES: Clinical data were extracted from electronic medical records and reviewed by a trained team of physicians. Neurological symptoms fall into three categories: central nervous system (CNS) symptoms or diseases (headache, dizziness, impaired consciousness, ataxia, acute cerebrovascular disease, and epilepsy), peripheral nervous system (PNS) symptoms (hypogeusia, hyposmia, hypopsia, and neuralgia), and skeletal muscular symptoms. Data of all neurological symptoms were checked by two trained neurologists. RESULTS: Of 214 patients studied, 88 (41.1%) were severe and 126 (58.9%) were non-severe patients. Compared with non-severe patients, severe patients were older (58.7 ± 15.0 years vs 48.9 ± 14.7 years), had more underlying disorders (42 [47.7%] vs 41 [32.5%]), especially hypertension (32 [36.4%] vs 19 [15.1%]), and showed less typical symptoms such as fever (40 [45.5%] vs 92 [73%]) and cough (30 [34.1%] vs 77 [61.1%]). Seventy-eight (36.4%) patients had neurologic manifestations. More severe patients were likely to have neurologic symptoms (40 [45.5%] vs 38 [30.2%]), such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]), impaired consciousness (13 [14.8%] vs 3 [2.4%]) and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]). CONCLUSION: Compared with non-severe patients with COVID-19, severe patients commonly had neurologic symptoms manifested as acute cerebrovascular diseases, consciousness impairment and skeletal muscle symptoms.

Atherosclerosis is a chronic progressive inflammatory disease of the large and medium-sized artery walls. The molecular mechanisms regulating the onset and progression of atherosclerosis remain unclear. T cells, one of the most common immune cell types in atherosclerotic plaques, are increasingly recognized as a key mediator in the pathogenesis of atherosclerosis. Th1 cells are a subset of CD4⁺ T helper cells of the adaptive immune system, characterized by the expression of the transcription factor T-bet and secretion of cytokines such as IFN-γ. Converging evidence shows that Th1 cells play a key role in the onset and progression of atherosclerosis. Besides, Th1 is the central mediator to orchestrate the adaptive immune system. In this review, we aim to summarize the complex role of Th1 cells in atherosclerosis and propose novel preventative and therapeutic approaches targeting Th1 cell-associated specific cytokines and receptors to prevent atherogenesis.

Low-density lipoprotein receptor–related protein-1 (LRP1) is a large endocytic and signaling receptor belonging to the LDL receptor (LDLR) gene family and that is widely expressed in several tissues. LRP1 comprises a large extracellular domain (ECD; 515 kDa, α chain) and a small intracellular domain (ICD; 85 kDa, β chain). The deletion of LRP1 leads to embryonic lethality in mice, revealing a crucial but yet undefined role in embryogenesis and development. LRP1 has been postulated to participate in numerous diverse physiological and pathological processes ranging from plasma lipoprotein homeostasis, atherosclerosis, tumor evolution, and fibrinolysis to neuronal regeneration and survival. Many studies using cultured cells and in vivo animal models have revealed the important roles of LRP1 in vascular remodeling, foam cell biology, inflammation and atherosclerosis. However, its role in atherosclerosis remains controversial. LRP1 not only participates in the removal of atherogenic lipoproteins and proatherogenic ligands in the liver but also mediates the uptake of aggregated LDL to promote the formation of macrophage- and vascular smooth muscle cell (VSMC)-derived foam cells, which causes a prothrombotic transformation of the vascular wall. The dual and opposing roles of LRP1 may also represent an interesting target for atherosclerosis therapeutics. This review highlights the influence of LRP1 during atherosclerosis development, focusing on its dual role in vascular cells and immune cells.

Objective—: P2Y ₁₂ is a well-recognized receptor expressed on platelets and the target of thienopyridine-type antiplatelet drugs. However, recent evidence suggests that P2Y ₁₂ expressed in vessel wall plays a role in atherogenesis, but the mechanisms remain elusive. In this study, we examined the molecular mechanisms of how vessel wall P2Y ₁₂ mediates vascular smooth muscle cells (VSMCs) migration and promotes the progression of atherosclerosis. Approach and Results—: Using a high-fat diet–fed apolipoprotein E–deficient mice model, we found that the expression of P2Y ₁₂ in VSMCs increased in a time-dependent manner and had a linear relationship with the plaque area. Moreover, administration of P2Y ₁₂ receptor antagonist for 12 weeks caused significant reduction in atheroma and decreased the abundance of VSMCs in plaque. In cultured VSMCs, we found that activation of P2Y ₁₂ receptor inhibited cAMP/protein kinase A signaling pathway, which induced cofilin dephosphorylation and filamentous actin disassembly, thereby enhancing VSMCs motility and migration. In addition, the number of P2Y ₁₂ -positive VSMCs was decreased in the carotid artery plaque from patients receiving clopidogrel. Conclusions—: Vessel wall P2Y ₁₂ receptor, which promotes VSMCs migration through cofilin dephosphorylation, plays a critical role in the development of atherosclerotic lesion and may be used as a therapeutic target for atherosclerosis.