COVID-19 and Neurological Impairment: Hypothalamic Circuits and Beyond

In December 2019, a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of Hubei, China. The virus infection, coronavirus disease 2019 (COVID-19), represents a global concern, as almost all countries around the world are affected. Clinical reports have confirmed several neurological manifestations in COVID-19 patients such as headaches, vomiting, and nausea, indicating the involvement of the central nervous system (CNS) and peripheral nervous system (PNS). Neuroinvasion of coronaviruses is not a new phenomenon, as it has been demonstrated by previous autopsies of severe acute respiratory syndrome coronavirus (SARS-CoV) patients who experienced similar neurologic symptoms. The hypothalamus is a complex structure that is composed of many nuclei and diverse neuronal cell groups. It is characterized by intricate intrahypothalamic circuits that orchestrate a finely tuned communication within the CNS and with the PNS. Hypothalamic circuits are critical for maintaining homeostatic challenges including immune responses to viral infections. The present article reviews the possible routes and mechanisms of neuroinvasion of SARS-CoV-2, with a specific focus on the role of the hypothalamic circuits in mediating the neurological symptoms noted during COVID-19 infection.     

Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus–host protein–protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host “self” proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development. Our analysis indicated that neurodegenerative diseases (NDs) have a higher number of disease-associated biological processes that can be modulated by SARS-CoV-2 via virus–host PPIs than neuropsychiatric disorders. The sequence similarity analysis indicated the presence of several matching 5-mer and/or 6-mer linear motifs between SARS-CoV-2 epitopes with autoreactive epitopes found in Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Myasthenia Gravis (MG) and Multiple Sclerosis (MS). The results include autoreactive epitopes that recognize amyloid-beta precursor protein (APP), microtubule-associated protein tau (MAPT), acetylcholine receptors, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NfL) and major myelin proteins. Altogether, our results suggest that there might be an increased risk for the development of NDs after COVID-19 both via autoreactivity and virus–host PPIs.     

急性脑血管病病人一氧化氮含量变化及其临床意义

目的了解急性脑血管病病人血液一氧化氮(NO)含量的变化情况,探讨NO在急性脑血管病发生发展过程中的作用和意义。方法采用硝酸酶还原法分别测定25例脑梗死、31例脑出血和20例蛛网膜下腔出血病人入院3d内的NO含量。结果脑出血、蛛网膜下腔出血和脑梗死病人血液NO含量均比正常对照组高(P<0.05);脑出血、蛛网膜下腔出血病人血液NO含量又较脑梗死病人高(P<0.05)。结论急性脑血管病病人存在高水平的血液NO含量,脑血管病人NO水平与病情严重程度相关,NO可能参与了急性脑血管病的病理过程。     

Behavioral,psychological, and clinical outcomes of Arabic-speaking people with type 2 diabetes during COVID-19 pandemic

AimsAssess self-care activities, health behaviors, self-efficacy, diabetes distress, challenges, and changes in diabetes treatment and clinical parameters among Arabic-speaking people with T2DM during the COVID-19 pandemic.MethodsA cross-sectional study was conducted at a tertiary hospital in the United Arab Emirates. The study instrument collected self-reported data using validated tools about health behaviors, self-efficacy, and diabetes distress, and challenges in accessing and using healthcare services during the pandemic and documented clinical data and treatment before and during the pandemic from medical records.Results206 patients participated with a mean age of 58.7 years and 15.7 years since diabetes diagnosis. Non-adherence to healthful eating and exercise was reported by 38.3% and 73.7%, respectively. Exercise was the self-care activity that decreased the most (36.8%). Most participants had low diabetes distress (85.9%). There were no significant differences in clinical parameters before and during the pandemic, and diabetes treatment was unchanged for 72.8% of participants. Having two or more challenges with accessing and using diabetes healthcare services was significantly associated with decreased adherence to healthy eating (p = 0.025) and exercise (p = 0.003).ConclusionsArabic-speaking people with T2DM appeared to maintain relatively similar self-care levels, except exercise, with no deterioration in clinical parameters compared to pre-pandemic.     

Behavioral symptoms,depression symptoms,and medication use in Michigan nursing home residents with dementia during COVID-19

Background

The COVID-19 pandemic significantly disrupted nursing home (NH) care, including visitation restrictions, reduced staffing levels, and changes in routine care. These challenges may have led to increased behavioral symptoms, depression symptoms, and central nervous system (CNS)-active medication use among long-stay NH residents with dementia.

Methods

We conducted a retrospective, cross-sectional study including Michigan long-stay (≥100 days) NH residents aged ≥65 with dementia based on Minimum Data Set (MDS) assessments from January 1, 2018 to June 30, 2021. Residents with schizophrenia, Tourette syndrome, or Huntington's disease were excluded. Outcomes were the monthly prevalence of behavioral symptoms (i.e., Agitated Reactive Behavior Scale ≥ 1), depression symptoms (i.e., Patient Health Questionnaire [PHQ]—9 ≥ 10, reflecting at least moderate depression), and CNS-active medication use (e.g., antipsychotics). Demographic, clinical, and facility characteristics were included. Using an interrupted time series design, we compared outcomes over two periods: Period 1: January 1, 2018–February 28, 2020 (pre-COVID-19) and Period 2: March 1, 2020–June 30, 2021 (during COVID-19).

Results

We included 37,427 Michigan long-stay NH residents with dementia. The majority were female, 80 years or older, White, and resided in a for-profit NH facility. The percent of NH residents with moderate depression symptoms increased during COVID-19 compared to pre-COVID-19 (4.0% vs 2.9%, slope change [SC] = 0.03, p < 0.05). Antidepressant, antianxiety, antipsychotic and opioid use increased during COVID-19 compared to pre-COVID-19 (SC = 0.41, p < 0.001, SC = 0.17, p < 0.001, SC = 0.07, p < 0.05, and SC = 0.24, p < 0.001, respectively). No significant changes in hypnotic use or behavioral symptoms were observed.

Conclusions

Michigan long-stay NH residents with dementia had a higher prevalence of depression symptoms and CNS active-medication use during the COVID-19 pandemic than before. During periods of increased isolation, facility-level policies to regularly assess depression symptoms and appropriate CNS-active medication use are warranted.     

Neurological Manifestations and Long-term Sequelae in Hospitalized Patients with COVID-19

Objective Various neurological manifestations have been increasingly reported in coronavirus disease 2019 (COVID-19). We determined the neurological features and long-term sequelae in hospitalized COVID-19 patients. Methods We retrospectively studied 95 consecutive hospitalized patients with COVID-19 between March 1 and May 13, 2020. Acute neurological presentations (within two weeks of the symptom onset of COVID-19) were compared between 60 non-severe and 35 severely infected patients who required high-flow oxygen. In the 12 ventilated patients (the most severe group), we evaluated neurological complications during admission, subacute neurological presentations, and neurological sequelae (51 and 137 days from the onset [median], respectively). Results Of the 95 patients (mean age 53 years old; 40% women), 63% had acute neurological presentations, with an increased prevalence in cases of severe infections (83% vs. 52%, p＜0.001). Impaired consciousness and limb weakness were more frequent in severe patients than in non-severe ones (0% vs. 49%; p＜0.001, and 0% vs. 54%; p＜0.001, respectively). In the most severe group (mean age 72 years old; 42% women), 83% of patients had neurological complications [cerebrovascular disease (17%), encephalopathy (82%), and neuropathy (55%)], and 92% had subacute neurological presentations [impaired consciousness (17%), higher brain dysfunction (82%), limb weakness (75%), and tremor (58%)]. Neurological sequelae were found in 83% of cases, including higher brain dysfunction (73%), limb weakness (50%), and tremor (58%). Conclusions Neurological manifestations are common in COVID-19, with the possibility of long-lasting sequelae.     

Statins,Nitric Oxide and Neovascularization

Several landmark clinical trials suggest that 3‐hydroxyl‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) have additional cardiovascular protective activity that may function independently of their ability to lower serum cholesterol. The cardiovascular protective effects of statins are partly caused by the activation of postnatal neovascularization. At therapeutic doses, statins promote proliferation, migration and survival of endothelial cells, induce mobilization and differentiation of bone marrow‐derived endothelial progenitor cells by stimulating the serine/threonine protein kinase Akt (also known as protein kinase B) and nitric oxide (NO) signal pathway. However, at excessive doses, statins may decrease protein isoprenylation as well as inhibit endothelial cell growth and migration. NO is an important signaling molecule that regulates a wide range of physiological and pathological processes in different tissues. There is substantial evidence that effective neovascularization requires endothelium‐derived NO. Statins have pleiotropic effects on the expression and activity of endothelial nitric oxide synthase (eNOS) and lead to improved NO bioavailability. NO plays an important role in the effects of statins on neovascularization. In this review, we focus on the effects of statins on neovascularization and highlight specific novel targets, such as endothelial progenitor cells and NO.     

卡托普利对缺血再灌注兔心肌一氧化氮及其合酶活性的影响

目的：探讨卡托普利（ｃａｐｔｏｐｒｉｌ）对局部缺血再灌注免心肌保护作用的机制。 方法：将１８只新西兰兔随机分３组（每组ｎ＝６）,对照组左冠状动脉前降支阻断３０分,再灌注９０分;卡托普利组阻断前３０分静脉注射卡托普利每 ２０分 ２ ｍｇ／ｋｇ,再灌注时再持续静脉注射卡托普利每 ９０分１ｍｇ／ｋｇ,假手术组环左冠状动脉前降支置线但不阻断血流。观察心肌一氧化氮合酶（ＮＯＳ）同工酶活性、过氧化物歧化酶活性、丙二醛含量、肌酸激酶含量及右心房血一氧化氮（ＮＯ）的变化,监测心肌功能。 结果：缺血再灌注心肌原生型ＮＯＳ（ＣＮＯＳ）活性（Ｐ＜０．００１）及总ＮＯＳ活性（Ｐ＜０．０１）显著下降,ＮＯ产生减少（Ｐ＜０．０５～０．０１）,卡托普利组缺血再灌注期间ＮＯ水平高于对照组（Ｐ＜０．０１）,再灌注３０分心肌ＣＮＯＳ活性（Ｐ＜０．０１）及总ＮＯＳ活性（Ｐ＜０．０５）显著高于对照组,心肌损害较对照组减轻。 结论：ＮＯ产生不足是心肌再灌注损伤的重要因素,卡托普利通过调节ＮＯＳ活性,维持正常ＮＯ水平起到保护作用。     

The relationship between COVID-19 and fibromyalgia syndrome: prevalence,pandemic effects,symptom mechanisms,and COVID-19 vaccines

Clinical Rheumatology - On March 11, 2020, the World Health Organization, realizing the level of spread worldwide and the severity of the condition, accepted coronavirus disease 19 (COVID-19) as a...     

美国国立神经疾病和卒中研究所-加拿大卒中网血管性认知障碍统一标准

背景和目的：1／3的个体会罹患卒中和（或）痴呆,而且,除卒中或痴呆外,2倍于此数的人会出现认知障碍。常用的卒中量表并不能评价认知功能,而痴呆的诊断标准则集中在认知障碍的晚期阶段,且在很大程度上偏向Alzheimer病（AD）的诊断。尚缺乏普遍公认的标准用于识别和描述存在认知障碍的个体,尤其是在早期阶段,而且特别是与血管因素有关的认知障碍或血管性认知障碍。方法：美国国立神经疾病和卒中研究所（MINDS）与加拿大卒中网（CSN）召集临床诊断、流行病学、神经心理学、脑影像学、神经病理学、试验模型、生物标记物、遗传学和临床试验方面的研究人员,为血管性认知障碍的描述和研究推荐一些最低限度的常用的临床和研究标准。结果：将这些讨论的结果发表于此。结论：一个统一标准的制定代表着使用、确认和改进过程中的第一步。使用相同的标准将有助于在认知障碍的早期阶段识别患者,使不同的研究具有可比性,并且通过整合知识来加速研究进展的步伐。     

Clinical and Radiological Profiles of COVID-19 Patients with Neurological Symptomatology: A Comparative Study

Patients with COVID-19 can require radiological examination, with chest CT being more frequent than neuro-imaging. The objective is to identify epidemiological, clinical and radiological factors considered as predictors of neurological involvement in patients with COVID-19 assessed by neuroimaging and to describe the neuroimaging findings. This retrospective study was performed with 232 consecutive confirmed COVID-19 patients, from two radiological units, which were divided into two groups: (1) those who underwent a brain CT/MRI scan (n = 35) versus (2) those who did not undergo the brain CT/MRI scan, but underwent only chest CT (n = 197). There was a statistically significant difference with associations regarding the COVID-19 brain scan group for: admission to ICU, greater severity of lung injuries, the use of a mechanical ventilator and sepsis. Statistical tendency was found for chronic renal failure and systemic arterial hypertension. Forty-percent of COVID-19 patients from the brain scan group were abnormal on brain CT and/or brain MRI (22.9% of the cases with bleeding or microbleeding, 8.6% with restricted diffusion lesions). One ischemic stroke case was associated with irregularity at the M1 segment of the right middle cerebral artery. There was a case of left facial nerve palsy with enhancement of the left geniculate ganglia. An analysis of the olfactory bulbs was possible in 12 brain MRIs and 100% had enhancement and/or microbleeding. In conclusion, a more severe COVID-19 disease from ICU, a more severe form of lung disease, the use of mechanical ventilator and sepsis were associated to the COVID-19 patients with neurological involvement who had undergone brain scans. Microvascular phenomenon was a frequent finding in the brain and olfactory bulbs evaluated by neuroimaging.     

Neurological symptoms and signs associated with COVID-19 in pediatric patients: a single-center experience

There is insufficient evidence on SARS-CoV-2 induced neurological effects. Studies on CNS involvement during COVID-19 in children are limited. This study aims to identify and manage the neurological signs and symptoms in COVID-19-infected pediatric patients during follow up and plan future follow-ups.Children diagnosed COVID-19 and hospitalized in the pediatric pandemic services, between March 18, 2020, and June 18, 2021, were included in the study. Children with underlying neurological disease were excluded from the study. Patient data retrieved from hospital files and medical records. Children divided into 2 groups, 1 and 2, based on the presence or absence of neurological findings.A total of 243 children received follow-ups in the pandemic wards, 35 (14.4%) of these patients had neurological findings. Major neurological manifestations were headache (n:17, 7%), seizure (n:4, 1.6%), and anosmia/hyposmia (n:17, 7%). The number of boys (n:13, 37.1%) was smaller than the number of girls (n:22, 62.9%) in Group 1. Group 1 showed higher blood leukocyte, lymphocyte, thrombocyte, AST, LDH, d-dimer values. Anosmia/hyposmia occurred more often in girls, anosmia and headache occurred more often over 9 years of age. Pulmonary and hematologic involvement was more common in children with anosmia and headache.Our study is one of the few studies on neurological involvement in COVID-19 in children. To the best of our knowledge, there is limited data on these subjects in the literature.     

Oxidative Stress, Nitric Oxide, and Diabetes

In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients.     

电针与认知行为治疗持续性躯体形式疼痛障碍的临床研究

目的研究电针、认知行为心理治疗与二者联合在抗抑郁药物治疗基础上治疗持续性躯体形式疼痛障碍的疗效的差别。方法对65名持续性躯体形式疼痛障碍患者追踪观察1年,治疗前将患者随机分为3组;在抗抑郁药物治疗基础上,一组接受电针治疗（简称电针组）;一组接受认知行为治疗（简称心理组）;一组接受电针联合认知行为治疗（简称电针心理治疗组）。对3组治疗前与后2、4、8周以及半年,1年各进行1次疼痛症状评分,汉密尔顿抑郁量表（HAMD）和汉密尔顿焦虑量表（HAMA）测评,以及1年后复发率的对比。结果电针及电针联合认知行为治疗组2周、4周时的疗效优于认知行为治疗组（P〈0.05）;1年时,认知行为治疗组与电针认知行为治疗组疗效相当,但明显优于电针治疗组（P〈0.05）;且二者复发率较电针治疗组低（P〈0.05）。结论在抗抑郁药物治疗基础上配合电针治疗能快速缓解患者的疼痛症状及焦虑抑郁情绪,而配合认知行为治疗能纠正患者的不良认知,从而减少持续性躯体形式疼痛障碍复发;故电针配合认知行为治疗是对持续性躯体形式疼痛障碍的更为有效的治疗方式。