Functional mutations of SARS-CoV-2: implications to viral transmission,pathogenicity and immune escape

The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.     

A Hierarchical Framework for Assessing Transmission Causality of Respiratory Viruses

Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing, and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for present and future pandemics of viral respiratory pathogens. We review the history of causality assessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierarchy of evidence to integrate clinical, epidemiologic, molecular, and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency, and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.     

青少年多囊卵巢综合征与其父母代谢综合征的相关性研究

目的探讨青少年多囊卵巢综合征（PCOS）与其父母代谢综合征（MBS）的相关性。方法选择2004年3月—2007年3月在浙江省慈溪市妇幼保健院与慈溪市人民医院的36例PCOS青少年患者（11～16岁）及其父母（35例母亲,19例父亲）、21例正常青少年（女,11～16岁）,进行其体质量指数（BMI）、腰围、血压测量,并检测其血清胆固醇（TC）、三酰甘油（TG）、雄性激素水平,同时进行糖耐量测定（OGTT）及超声检查多囊卵巢情况。结果①PCOS患者的父亲94%肥胖或超重,79%患有MBS。②PCOS患者的母亲停经前36%患MBS,明显高于患PCOS者（≤20%）。③PCOS患者的多囊卵巢特征极少数遗传于母亲,其主要遗传于父亲的MBS因素（P=0.008）。④PCOS患者中28%患有MBS。结论青少年PCOS在根本上是由其父亲患有MBS遗传因素所致。     

麻仁软胶囊对便秘型 IBS 大鼠模型肠黏膜 5 - HT 含量的影响

目的研究麻仁软胶囊对便秘型肠易激综合征（IBS）模型大鼠5-HT含量的影响,探讨麻仁软胶囊治疗便秘型IBS的作用机制。方法将大鼠分为中药组、西药组、模型组、正常组4组,采用冰水灌胃慢性刺激方法将前3组复制为大鼠便秘型IBS模型,观察各组大鼠粪便的数量及性状,于第14天造模成功后中药组灌中药,西药组灌西药,模型组及正常组予以正常饮食。于第28天将各组大鼠进行解剖取其部分结肠,将其做成石蜡切片,在HE染色下和SABC免疫组化染色下镜下观察各组肠组织变化及肠黏膜上5-HT的含量。结果IBS模型大鼠5-HT表达增高,出现IBS临床症状;经麻仁软胶囊干预后,大鼠5-HT表达降低。结论麻仁软胶囊可增高大鼠肠道敏感性,其作用机制与降低大鼠结肠5-HT表达、增高肠道敏感性有关。     

COVID-19 and Guillain-Barré syndrome: A single-center prospective case series with a 1-year follow-up

Single reports of Guillain-Barré syndrome (GBS) have been reported worldwide during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. While case reports are likely to be biased toward uncommon clinical presentations, systematic assessment of prospective series can highlight the true clinical features and spectrum. In this prospective, observational study, we included all consecutive patients who developed GBS. In patients with SARS-CoV-2 infection as antecedent, the time-gap between the infection and GBS onset had to be ≤30 days. The referral was a neurological University Research Hospital, in the Italian Region more severely involved by the pandemic, and hospitalizing both COVID+ and non-COVID neurological diseases. Clinical, laboratory, cerebrospinal fluid, and electromyographic features of GBS diagnosed between March 2020 and March 2021 were compared to a retrospective series of GBS diagnosed between February 2019 and February 2020 (control population). Nasopharyngeal swab was still positive at GBS onset in 50% of patients. Mild-to-moderate COVID-related pneumonia, as assessed by X-ray (6 patients) or X-ray plus computerized tomography (2 patients) co-occurred in 6 of 10 patients. GBS diagnosed during the pandemic period, including 10 COVID-GBS and 10 non–COVID-GBS, had higher disability on admission (P = .032) compared to the GBS diagnosed between February 2019 and 2020, possibly related to later hospital referral in the pandemic context. Compared to non–COVID-GBS (n = 10) prospectively diagnosed in the same period (March 2020–2021), post–COVID-GBS (n = 10) had a higher disability score on admission (P = .028), lower sum Medical Research Council score (P = .022) and lymphopenia (P = .025), while there were no differences in GBS subtype/variant, severity of peripheral involvement, prognosis and response to treatment. Cerebrospinal fluid search for SARS-CoV-2 RNA and antiganglioside antibodies were negative in all COVID+ patients. Temporal clustering of cases, coinciding with the waves of the pandemic, and concomitant reduction of the incidence of COVID-negative GBSs may indicate a role for SARS-CoV-2 infection in the development of GBS, although the association may simply be related to a bystander effect of systemic inflammation; lack of prevalence of specific GBS subtypes in post–COVID-GBS also support this view. GBS features and prognosis are not substantially different compared to non–COVID-GBS.     

Refeeding Syndrome: A Critical Reality in Patients with Chronic Disease

Malnutrition is one of the most frequent metabolic challenges in the population of chronically ill patients. This results in increased administration of nutritional therapy in inpatient settings, which poses the risk of side effects, in particular, the development of refeeding syndrome. If not managed accordingly, it leads to a significant rise in morbidity and mortality. However, despite its importance, evidence-based recommendations on the management of refeeding syndrome are largely lacking, and only a few randomized controlled trials have been conducted. In light of this, the aim of this review is to raise awareness of refeeding syndrome in chronically ill patients by critically reviewing recent literature and providing a short overview as well as diagnosis and treatment algorithms of this underreported metabolic condition. In summary, recent findings suggest undergoing risk assessment and stratification for every patient receiving nutritional therapy. According to this, adaptation of energy and fluid support during the replenishment phase should be implemented in the nutritional therapy for patients at high risk. Additionally, continuous monitoring should take place, and appropriate actions should be initiated when necessary.     

特步他林并布地奈德治疗对急性支气管哮喘患者IL-5、IL-10及TNF-α的影响

目的研究急性支气管哮喘(BA)经特步他林并布地奈德治疗后白介素-5(IL-5)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的变化。方法选取2016年1月至2020年12月商丘市中医院收治的122例急性BA患者的临床资料进行分析,根据不同治疗方法分为研究组(n=62,特步他林+布地奈德)和对照组(n=60,特步他林),比较两组临床疗效、肺功能[用力肺活量(FVC)、1秒用力呼气容器(FEV1)、1秒用力呼气容积占用力肺活量的百分比(FEV1/FVC%)、治疗前后IL-5、IL-10、TNF-α变化及不良反应情况。结果研究组总疗效(93.55%)高于对照组(81.67%),差异有统计学意义(P<0.05)。治疗后两组FVC、FEV1、FEV1/FVC%均较治疗前升高,且研究组高于对照组,差异具有统计学意义(P<0.05)。治疗后两组IL-5、TNF-α水平均降低,且研究组低于对照组,两组IL-10水平均上升,且研究组高于对照组,差异有统计学意义(P<0.05)。两组不良反应率比较差异无统计学意义(P>0.05)。结论特步他林与布地奈德联合治疗急性BA...     

Associations between Abnormal Eating Styles and Irritable Bowel Syndrome: A Cross-Sectional Study among Medical School Students

(1) Background: Few studies have investigated the association between eating styles and IBS. This study aimed to explore the association between abnormal eating styles and irritable bowel syndrome (IBS). (2) Methods: This cross-sectional study investigated students in China Medical University and Shenyang Medical College. Eating styles were evaluated by the Dutch Eating Behavior Questionnaire (DEBQ), and IBS was diagnosed according to Rome III criteria. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). (3) Results: A total of 335 students were diagnosed with IBS. Students with the total scores in tertile 2 and 3 had 1.29 times and 2.75 times higher risk of IBS than students with the total scores in tertile 1, respectively. Simultaneously, the risk of IBS in the tertile 3 of external eating, emotional eating, and restraint eating trends was 3.87 times, 2.71 times, and 3.82 times higher than that of tertile 1, respectively. (4) Conclusions: this study showed that a high score in both total eating styles and each eating style was associated with the odds of having IBS and suggested that the psychological factors behind eating styles may play a critical role in controlling the IBS.     

Pharmacological Studies in Hospitalized COVID-19 Patients in Belgium: We Could Do Better

Belgium has actively participated in clinical research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the beginning of the pandemic to help identify effective and safe treatments for COVID-19. The objective of this review is to provide a picture of the clinical studies carried out in hospitalized patients with COVID-19 in Belgium. We collected data on all randomized, interventional trials in patients with COVID-19 that were registered on two recognized clinical trial registers, started enrollment before 31 December 2021, and included at least one patient in a Belgian center. Data were collected concerning the therapies investigated and the nature of the trials performed. Thirty-three hospitals (32% of all Belgian hospitals) participated in at least one of 28 trials (13 sponsored by the industry and 15 by academic centers) on therapeutics for COVID-19 in hospitalized patients: 7 (25%) evaluated antivirals, 17 (61%) immunomodulators, 2 (7%) anti-coagulants, and 1 (3%) nitric oxide to improve respiratory function. Nineteen (68%) were phase II trials. Only three (11%) of the trials were international platform trials. Despite numerous trials, less than 3% of all Belgian patients hospitalized with COVID-19 participated in a clinical trial on therapeutics. As in many other countries, more efforts could have been made to avoid running small, under-powered, mono- or bicenter trials, to create better collaboration between the different Belgian hospitals, and to participate in more international clinical trials, and more specifically in adaptive, platform trials.     

Association between maternal gestational diabetes mellitus and high‐sensitivity C‐reactive protein levels in 8‐year‐old children: The Yamanashi Adjunct Study of the Japan Environment and Children’s Study (JECS)

Gestational diabetes mellitus (GDM) is one of the most common pregnancy‐related complications; it is associated with adverse pregnancy outcomes and metabolic disorders in offspring, consistent with the concept of the developmental origins of health and disease. This cohort study of women without diabetes (n = 761), who were part of the Yamanashi Adjunct Study of the Japan Environment and Children’s Study, aimed to explore the associations between maternal GDM and their offspring’s level of high‐sensitivity C‐reactive protein (hsCRP), a biomarker of inflammatory and cardiovascular diseases. We analyzed the associations between GDM and the offspring’s hsCRP levels using a multiple logistic regression model. A mother with GDM significantly increased the risk for high hsCRP level by 4.07‐fold (≥2.0 mg/L) in the child. As such, maternal GDM was significantly associated with increased serum hsCRP levels in 8‐year‐old children.