COVID-19: Review on Its Etiology,Pathogenesis, and Existence in Humans

The world is facing a new healthcare crisis with the rise and spread of novel coronavirus since December 2019. Also known as Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), the disease associated with SARSCoV-2 is even called COVID-19. The infection is said to have originated from the bat community and transmitted to humans through an intermediate host (yet unknown) in Wuhan, in the Hubei region of China. COVID-19 is having a pulverizing impact on the scientific community. As of August 13, 2020, the number of confirmed cases had reached up to 20,439,814 and the death toll to 744,385, affecting more than 188 territories across the globe. In these difficult times, the world is looking towards research and clinical work from different scientific communities to lead the way to a solution to the issue. In this review, we are focusing on COVID-19 emergence, pathogenicity, and existence in humans, as well as the SARS-CoV-2 infection mechanism and its similarities to previous coronavirus strains.     

Should we continue breastfeeding after SARS-CoV-2 infection or mRNA vaccination?

The coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a potential threat to infant health. The World Health Organization recommended that the benefits of breastfeeding far outweigh the potential risk of transmission, but there is no denying that the current evidence is insufficient. Moreover, although the COVID-19 mRNA vaccine has played an effective role in protection against infection, individuals have increasing concerns about the safety of breastfeeding after vaccination, and which have caused some breastfeeding women to postpone vaccination or stop breastfeeding early. Thus, in this review, we provide an in-depth discussion of whether SARS-CoV-2 and the vaccine will affect babies through breast milk. On one hand, only a very small number of milk samples were identified positive for viral RNA and almost impossible to be live virus particles. The milk of most lactating women after vaccination did not contain vaccine-related mRNA and polyethylene glycol. On the other hand, the antibodies and biologically active molecules like lactoferrin are abundant in the milk of lactating women who have been infected or vaccinated, which can provide potential protection against infants’ respiratory and gastrointestinal infections. Therefore, in terms of implications for clinical practice, the results of our study support that lactating women who have been infected or vaccinated should be encouraged to breastfeed their infants under the premise of taking appropriate sanitary measures.     

dbSCI: A manually curated database of SARS-CoV-2 inhibitors for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen of the ongoing coronavirus disease 2019 (COVID-19) global pandemic. Here, by centralizing published cell-based experiments, clinical trials, and virtual drug screening data from the NCBI PubMed database, we developed a database of SARS-CoV-2 inhibitors for COVID-19, dbSCI, which includes 234 SARS-CoV-2 inhibitors collected from publications based on cell-based experiments, 81 drugs of COVID-19 in clinical trials and 1305 potential SARS-CoV-2 inhibitors from bioinformatics analyses. dbSCI provides four major functions: (1) search the drug target or its inhibitor for SARS-CoV-2, (2) browse target/inhibitor information collected from cell experiments, clinical trials, and virtual drug screenings, (3) download, and (4) submit data. Each entry in dbSCI contains 18 types of information, including inhibitor/drug name, targeting protein, mechanism of inhibition, experimental technique, experimental sample type, and reference information. In summary, dbSCI provides a relatively comprehensive, credible repository for inhibitors/drugs against SARS-CoV-2 and their potential targeting mechanisms and it will be valuable for further studies to control COVID-19.     

SARS-CoV-2 induced myocarditis: Current knowledge about its molecular and pathophysiological mechanisms

The existence of an inflammatory process in the heart muscle, related to a progressive worsening of myocardial function, different etiopathogenetic mechanisms concur and often overlap, thus making the diagnosis and the therapeutic approach complex. As the COVID-19 pandemic progresses, the effects of the disease on the organ systems and in particular on the cardiovascular system are becoming more and more profound. Cardiac involvement is a well-known event with a high percentage of findings in the heart’s magnetic field, even in asymptomatic areas. There are numerous uncertainties regarding their evolution, in the long and short term, due not only to a difficult to determine the varied clinical expression and the rarely performed intramyocardial biopsy which additionally presents diagnostic problems but also in part to different clinical prognosis. Today, the new SARS-CoV-2 virus that uses the angiotensin converting enzyme 2 (ACE2) which is present at high levels in myocardial cells as its entrance it can create even severe heart injury. The pathophysiology in all of these cases can involve multiple immune and non-immune mechanisms within organs and vessels and can be occur in the clinical phases. Possible mechanisms of direct and indirect myocardial infarction in patients with COVID-19 include additional lesion and oxygen-rich and generalized inflammation response with myocardial immune hyperactivity (myocarditis). Therefore, these can occur through the excessive release of cytokines, the presence of thrombocytopenia, endocrine damage, heart failure, arrhythmias and more. Patients can show average signs of myocardial damage, and some develop spontaneous cardiac complications, such as heart failure, arrhythmias and, rarely, rare cardiogenic disorders. Pathophysiology in all of these may involve multiple mechanisms within the cytokine cephalic membrane, endocrine damage and thrombogenicity. The diagnosis of this myocardial injuri is mainly based on the myocardial enzyme troponin. This viewpoint paper explains today’s knowledge on viral myocarditis, in particular that from SARS-CoV-2 infection, if there is a connection with other possible biomolecular pathogenetic factors that can influence its natural course. In fact, it is for this reason that the pathogenetic mechanisms are analyzed and described. At the same time, its possible interaction with other parameters that are documented risk factors for cardiovascular disease was examined. Although these biomolecular findings were mainly related to necrotic parts of the myocardium, it is important to recognize that myocardial damage early for a better approach and prognosis.     

Indian medicinal plants are effective in the treatment and management of COVID-19

Indian medicinal plants are referred to as the “nectar of life” owing to their phytochemicals and bioactive complexes that are beneficial in treating diseases. Coronavirus disease 2019 (COVID-19) is a global health issue without any proper medication. The indigenous plants of India can be exploited to control the precise signs of SARS-CoV-2. The Ministry of AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) has advised routine usage of medicinal plants for COVID-19. Medicinal plants like Zingiber officinalis, Azadirachta indica, Ocimum sanctum, Nigella sativa, Withania somnifera, Curcuma longa, Piper nigrum, Allium sativum, Tinospora cordifolia, etc. have immunity-boosting, antiviral, antibacterial, antioxidant and anti-inflammatory actions that can suppress and treat symptoms of COVID-19. In vitro, in vivo as well as in silico validation, these phytochemicals can help us to manage and treat COVID-19 disease. This integration of traditional knowledge in the prophylaxis of corona infection and current skills validating it for the development of precise and powerful therapeutic approaches will more efficiently resolve different clinical aspects of COVID-19. The review focuses on both traditional and emergent methods to prevent and treat COVID-19 with various Indian medicinal plants along with their phytochemicals.     

Identification of SARS-CoV-2 by gold nanoparticles

The SARS-CoV-2 outbreaks highlighted the need for effective, reliable, fast, easy-to-do and cheap diagnostics procedures. We pragmatically experienced that an early positive-case detection, inevitably coupled with a mass vaccination campaign, is a milestone to control the COVID-19 pandemic. Gold nanoparticles (AuNPs) can indeed play a crucial role in this context, as their physicochemical, optics and electronics properties are being extensively used in photothermal therapy (PTT), radiation therapy (RT), drug delivery and diagnostic. AuNPs can be synthesized by several approaches to obtain different sizes and shapes that can be easily functionalized with many kinds of molecules such as antibodies, proteins, probes, and lipids. In addition, AuNPs showed high biocompatibility making them useful tool in medicine field. We thus reviewed here the most relevant evidence on AuNPs as effective way to detect the presence of SARS-CoV-2 antigens. We trust future diagnostic efforts must take this ‘old-fashioned’ nanotechnology tool into consideration for the development and commercialization of reliable and feasible detection kits.     

新冠病毒蛋白及其细胞受体ACE2翻译后修饰的质谱分析

新冠肺炎(COVID-19)在全世界范围内造成了巨大的健康危机和不可估量的损失.新出现的变种病毒株表明,新冠病毒(SARS-CoV-2)可能会像流感病毒一样在人类社会中继续流行,成为一种长久的健康威胁.控制新冠病毒的传染和开发有效的治疗方法迫在眉睫.因此,找到合适的生物标志物以表明病理和生理状态是当务之急.蛋白质是生命...     

Toward an optimized strategy of using various airway mucus clearance techniques to treat critically ill COVID-19 patients

Coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is still threatening the human life and society throughout the world. For those critically ill patients, mechanical ventilation (MV) is essential to provide life support during treatment. However, both the virus infection and MV disrupt the balance between secretion and elimination of airway mucus and lead to mucus accumulation in the lung. Postmortem examination verified that the lungs in patients died of COVID-19 are indeed filled with sticky mucus, suggesting a great need to improve airway mucus clearance in critically ill COVID-19 patients. Therefore, it may be helpful to comprehensively review the current understanding regarding the changes of biochemical and rheological features of airway mucus associated with the disease, as well as the physiological principles and algorithm to decide airway clearance techniques suitable for the critically ill COVID-19 patients. Based on these considerations, optimized strategies may be developed to eliminate the airway mucus accumulated in the airways of critically ill COVID-19 patients.     

Structural characterization of β-propiolactone inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles

The severe COVID-19 pandemic drives the research toward the SARS-CoV-2 virion structure and the possible therapies against it. Here, we characterized the β-propiolactone inactivated SARS-CoV-2 virions using transmission electron microscopy (TEM) and atomic force microscopy (AFM). We compared the SARS-CoV-2 samples purified by two consecutive chromatographic procedures (size exclusion chromatography [SEC], followed by ion-exchange chromatography [IEC]) with samples purified by ultracentrifugation. The samples prepared using SEC and IEC retained more spikes on the surface than the ones prepared using ultracentrifugation, as confirmed by TEM and AFM. TEM showed that the spike (S) proteins were in the pre-fusion conformation. Notably, the S proteins could be recognized by specific monoclonal antibodies. Analytical TEM showed that the inactivated virions retained nucleic acid. Altogether, we demonstrated that the inactivated SARS-CoV-2 virions retain the structural features of native viruses and provide a prospective vaccine candidate.     

Relaxation of the mouse pubic symphysis during late pregnancy is not accompanied by the influx of granulocytes

In some animals, such as mice and guinea pigs, a hormonally controlled mechanism increases the flexibility of the pubic symphysis and enhances the cervical remodeling necessary for safe delivery. Cervical ripening during pregnancy is associated with a paradoxical influx of leukocytes. However, the changes in cell metabolism during relaxation of the mouse pubic symphysis for delivery have not been extensively studied. In this work, we used light microscopy and transmission and scanning electron microcopy, as well as immunohistochemistry and Western blotting for MMP-8, to investigate the involvement of granulocytes or resident stromal cells in the relaxation of the virgin pubic symphysis during late pregnancy (days 18 and 19, before delivery) in vivo and in explanted joints. MMP-8 was studied because this collagenase is a hallmark for cervical ripening associated with the influx of granulocytes during late pregnancy. Extensive dissolution and disorganization of the extracellular matrix was seen around fibroblastic-like cells in late pregnancy. In contrast to the cervix (positive control), morphological and immunohistochemical analyses revealed that there was no characteristic cellular inflammatory response in the interpubic tissue. Staining for MMP-8 was observed in chondroid and fibroblastic-like cells of virgin and relaxed interpubic ligament, respectively. However, no granulocytes were seen during the extensive remodeling of the pubic joint in late pregnancy. These results indicate that constitutive stromal cells may have an important role in tissue relaxation during remodeling of the pubic symphysis in pregnancy.     

Diagnostic and prognostic significance of the lymphocyte/C-reactive protein ratio,neutrophil/lymphocyte ratio,and D-dimer values in patients with COVID-19

In this study, our aim was to examine the diagnostic and prognostic significance of lymphocyte/C-reactive protein ratio (LCR), neutrophil/lymphocyte ratio (NLR) and D-dimer parameters in COVID-19 infection. The LCR, NLR, neutrophil count, mean platelet volume (MPV), C-reactive protein (CRP), and D-dimer parameters were evaluated retrospectively. This was a retrospective cohort study with 1000 COVID-19 positive and 1000 healthy control groups, all over the age of 18 years. Odds ratio (OR) and 95% confidence interval (CI) values were calculated for each parameter found to be statistically significant in the univariate and multivariate logistic regression models. Herein, 127 (12.7%) of the COVID-19⁺ patients, whose data was included in this study, died. The neutrophil, MPV, CRP, D-dimer, and NLR values were higher in the COVID-19⁺/deceased group than in the COVID-19⁺/alive and control groups (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001). The lymphocyte and LCR values were lower in the COVID-19⁺/deceased group than in the COVID-19⁺/alive and control groups (p < 0.001, p < 0.001). Variables with statistically significance in predicting COVID-19 infection were lymphocyte, LCR, D-dimer, NLR, CRP, MPV, PLT, and neutrophil values. Statistically significant variables in predicting mortality due to COVID-19 were LCR, CRP, NLR, lymphocyte, D-dimer, neutrophil, and MPV values. A low LCR and high NLR are associated with the presence, prognosis, and mortality due to COVID-19. LCR and NLR parameters can thus be used in clinical monitoring to reduce morbidity and mortality rates.     

Intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome via activating macrophage-angiogenesis-related androgen signaling

The development of polycystic ovary syndrome (PCOS) is closely related to the chronic inflammatory and obese. Recent studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling, but the underlying mechanisms have not been clarified. In this study, we established a model of PCOS in the offspring rats by high androgen exposure during late pregnancy in parental and established a female rat macrophage eliminating model by rejection of clodronate liposome. Then, the offspring rat macrophage phenotype in offspring female rat adipose tissue, and levels of testosterone, angiogenic factors (PDGF and VEGF) and inflammatory factors (TNF-α and MCP-1) were investigated. By coculture of RAW264.7 macrophage with adipocytes or C166 endothelial cells (ECs), the mobility of adipocytes, and the ECs function with associated signalling pathway were detected by using of androgen inhibitor Apalutamide, NF-κB inhibitor JSH-23 and ERK1/2 inhibitor LY3214996. It was found that high androgen exposure during late pregnancy led to increased testosterone levels and overweight and obesity, increased size and reduced number of subcutaneous and intra-abdominal adipocytes, and increased secretion of TNF-α and MCP-1 in female rats in the offspring. Eliminating macrophages significantly increased adipocytes and angiogenesis in offspring of rats with intrauterine high androgen, and reduced TNF-α and MCP-1. Macrophages promoted mobility of adipocytes, and inhibited proliferation, migration, tube formation of ECs under hyperandrogenic condition, which were significantly inhibited by Apalutamide, JSH-23 and LY3214996. Thus, intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome through increasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis via androgen/NF-κB/ERK1/2 signalling pathway.     

Involvement of the choroid plexus in central nervous system inflammation

During inflammatory conditions in the central nervous system (CNS), immune cells immigrate into the CNS and can be detected in the CNS parenchyma and in the cerebrospinal fluid (CSF). The most comprehensively investigated model for CNS inflammation is experimental autoimmune encephalomyelitis (EAE), which is considered the prototype model for the human disease multiple sclerosis (MS). In EAE autoagressive CD4(+), T cells gain access to the CNS and initiate the molecular and cellular events leading to edema, inflammation, and demyelination in the CNS. The endothelial blood-brain barrier (BBB) has been considered the obvious place of entry for the circulating immune cells into the CNS. A role of the choroid plexus in the pathogenesis of EAE or MS, i.e., as an alternative entry site for circulating lymphocytes directly into the CSF, has not been seriously considered before. However, during EAE, we observed massive ultrastructural changes within the choroid plexus, which are different from changes observed during hypoxia. Using immunohistochemistry and in situ hybridization, we observed expression of VCAM-1 and ICAM-1 in the choroid plexus and demonstrated their upregulation and also de novo expression of MAdCAM-1 during EAE. Ultrastructural studies revealed polar localization of ICAM-1, VCAM-1, and MAdCAM-1 on the apical surface of choroid plexus epithelial cells and their complete absence on the fenestrated endothelial cells within the choroid plexus parenchyme. Furthermore, ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelium mediated binding of lymphocytes via their known ligands. In vitro, choroid plexus epithelial cells can be induced to express ICAM-1, VCAM-1, MAdCAM-1, and, additionally, MHC class I and II molecules on their surface. Taken together, our observations imply a previously unappreciated function of the choroid plexus in the immunosurveillance of the CNS.     

国资委召开部分重点行业中央企业经济运行工作座谈会

4月9日,国资委召开部分重点行业中央企业经济运行工作座谈会,分析新冠肺炎疫情对中央企业生产经营的影响及企业面临的困难挑战,研究应对举措。国资委党委书记、主任郝鹏主持会议并讲话强调,要认真贯彻落实习近平总书记关于统筹推进新冠肺炎疫情防控和经济社会发展工作的系列重要讲话精神和党中央决策部署,指导推动中央企业在常态化疫情防控中加快复工复产,尽最大努力把疫情造成的损失降到最低限度,奋力实现全年目标任务,为确保实现决胜全面建成小康社会、决战脱贫攻坚目标任务作出更大贡献。国资委党委委员、副主任翁杰明、任洪斌出席会议。     

全球战疫 共克时艰——中国工程机械企业在行动

目前,随着新冠肺炎疫情升级成为全球性大流行病,世界各地都正在面临病毒的侵袭。据世界卫生组织3月15日公布的最新数据显示,中国以外新冠肺炎确诊病例达到72469例。其中欧洲疫情尤其严重。面对当前日趋严重的国际疫情形势,加强国际协作,共克时艰,成为又一个新的抗疫重点。     

供应链中断情境下考虑政府补贴的恢复策略

新冠疫情对全球供应链产生了深远影响,主要表现在产能和需求的同时中断.为探究供应链中断情境下政府补贴策略对供应链恢复的影响,以疫情期间低需求产品作为研究对象,将政府对产能和需求中断的补贴选择作为恢复策略的切入点,以供应链成员的累计利润作为恢复指标,运用系统动力学构建"制造商—配送中心"二级供应链,并仿真模拟部分中断和完全...     

Mesenchymal stem cells,the secretome and biomaterials: Regenerative medicine application

Mesenchymal stem cells (MSCs) are multipotent cells usually isolated from bone marrow, endometrium, adipose tissues, skin, and dental pulp. MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science. Recently, MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment. Different approaches to evaluate the future of biomaterials and stem cell properties have been developed. However, misconceptions and ethical issues still exist, such as MSCs being non-angiogenic, anti-apoptotic, and immunoregulatory competencies. Embryonic stem cells isolation primarily requires the consent of donors and can include the killing of fertilized eggs. These issues generate questions related to ethical and moral issues. However, MSCs have gained considerable attention for tissue regeneration owing to their differentiation ability with immunomodulatory effects. They are capable of secreting a broad range of biomolecules such as proteins, nucleic acids, exosomes, microRNAs, and membrane vesicles, collectively known as secretomes. Secretomes are released in response to the surrounding microenvironment. In this article, we briefly address topics related to the therapeutic potential of MSCs as an advanced approach in the field of regenerative medicine and various perspectives.     

Adrenomedullin has multiple roles in disease stress: development and remission of the inflammatory response

The upregulation of adrenomedullin (AM) gene expression and increases in systemic circulatory as well as localized tissue AM concentrations is well coordinated with the onset and progression of trauma, infection, and sepsis. As such, the coordinated change in AM suggests a key role for this peptide in the inflammatory response. By clinical definition, the process of inflammation constitutes an orchestrated cascade of localized tissue and systemic responses to immunological challenges. Classical responses to the onset of disease stresses are manifested in the timely elaboration of humoral, blood-borne signal effectors (such as adrenocortical and locally produced tissue hormones, immune cytokines, and inorganic signals such as nitric oxide) as well as patterned migration and infiltration of circulating bone marrow-derived cells (mononuclear cells such as monocyte-macrophages and polymorphonuclear cells like neutrophils) largely associated with or delivered through the vascular system. The body's attempts to combat acute infection to restore homeostatic equilibrium are further compromised by underlying disease situations. Atherosclerosis, diabetes, and cardiovascular disease, as well as nutritional metabolic derangements and persistent subclinical infection perturb the regulatory feedback loops necessary for proper control of response effectors like hormones and cytokines. When imbalances occur, tissue necrosis can ensue as driven by free radical damage to cell components. A true appreciation of the inflammatory response can only be grasped through an integrative approach in which the relationship between the different physiological systems is viewed in terms of a changing, dynamic interaction. In essence, the inflammatory response can be thought of in three phases: a period of severity assessment, a period of remediation, and a period of homeostatic restoration. Indeed, AM has differential effects on cellular metabolism, immune function, endocrine function, and cardiovascular function. This peptide appears to play a pivotal role in both reprioritizing the biological needs of tissues and organs during the three phases of inflammatory response as well as a role in restoring homeostatic equilibrium to the body.