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During the actual pandemic of COVID-19, it has become clear that the virus causing this devastating disease, SARS-CoV2, targets not only the lungs but also other organs. In this article, we discuss the known or suspected interactions between the virus and the kidneys, as well as their clinical presentations. We also discuss how the pandemic has altered the activities of nephrologists and the logistics of a Swiss dialysis center.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.
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Background: Although our understanding of immunopathology in the risk and severity of COVID-19 disease is evolving, a detail of immune response in long-term consequences of COVID-19 infection remains unclear. Recently, few studies have detailed the immune and cytokine profiles associated with PASC. However, dysregulation of immune system driving pulmonary PASC is still largely unknown. Method(s): To characterize the immunological features of PPASC, we performed droplet-based scRNA-sequencing using 10X genomics to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from participants naive to SARS-CoV-2 (NP, n=2) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC, n=2). Result(s): Analysis of more than 34,000 PBMCs by integrating our dataset with previously reported control datasets generated cell distribution and identified 11 immune cell types based on canonical gene expression. The proportion of myeloid-lineage cells (CD14+monocyte, CD16+monocyte, and dendritic cells) and platelets were increased in PPASC compared with those of NP. Specifically, PPASC displayed up-regulation of VEGFA and transcription factors, such as ATF2, ELK, and SMAD in myeloid-lineage cells. Also, TGF-beta and WNT signaling pathways were up-regulated in these cell population. Cell-cell interaction analysis identified that myeloid-lineage cells in PPASC participated in regulation of fibrosis and immune response, such as VEGFA (increased) and MIF (decreased) interactions. Conclusion(s): Together, this study provides high-resolution insights into immune landscape in PPASC. Our results emphasize differences in myeloid lineage-mediated fibrosis and immunity between PPASC and NP, suggesting they could act as potential pathological drivers of PPASC. (Figure Presented).
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Introduction: Indicators that assess relationships among leukocytes may inform more and/or earlier than those measured in isolation. Method(s): Blood leukocyte differential counts collected from 101 Mayo Clinic COVID-19 patients were related to later outcomes following two approaches: (i) as unstructured data (e.g., lymphocyte percentages) and (ii) as data structures that assess intercellular interactions. Analyzing the same primary data, it was asked whether information contents differed among methods and/or when two sets of structured indicators are used. Result(s): While unstructured data did not distinguish survivors from non-survivors (Fig. 1, rectangle A), one data structure (here identified with letters expressed in italics) exhibited one perpendicular inflection that differentiated two patient groups (B). Two survivor-related observations were also distinguished from the remaining data points (B). A second data structure also revealed a single line of observations and a perpendicular data inflection (C), while more (four) patient groups were identified (D). Four validations were conducted: (i) increasing mortality levels among contiguous data subsets (0, 7.1, 16.2, or 44.4%) suggested construct validity (D);(ii) internal validity was indicated because 22 of the 45 survivors detected by the first data structure were also captured by the second one;(iii) the analysis of patients that differed in address, co-morbidities and other aspects supported external validity;and (iv) quasi non-overlapping data intervals predicted statistical validity (E, F). The structured approach also uncovered new and/ or dissimilar information: different leukocyte-related ratios explained the clusters identified in these analyses (E, F). Conclusion(s): Structured data may yield more information than methods that do not assess multicellular interactions. Possible applications include daily, longitudinal, and personalized analysis of hospital data.
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The human pandemic caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in December, 2019 is still continuing in various parts of the world. The SARS-CoV-2 has evolved through sporadic mutations and recombination events and the emergence of alternate variants following adaptations in humans and human-to-animal transmission (zooanthraponosis) has raised concerns over the efficacy of vaccines against new variants. The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV- 2-related viruses in bats and pangolins. A recent report of back-andforth transmission of SARS-CoV-2 between humans and minks on mink farms in the Netherlands has sparked widespread interest in zooanthroponotic transmission of SARS-CoV-2 followed by reemergence to infect human populations. The risk of animal to human transmission depends on virus-host interaction in susceptible species that may be short-term or long term risks. The short term risk might be due to infection to humans during the viremic stage in susceptible animals. The long term risk might be either due to persistence of the virus at population level or latency of infection leading to risk of evolution and re-emergence of the virus. Experimental studies have identified a range of animals that are susceptible and permissive to SARS-CoV-2 infection viz. cats, ferrets, hamsters, mink, non-human primates, tree shrews, raccoon dogs, fruit bats, and rabbits. The health impacts of SARS-CoV-2 infection in animals are unknown and it is likely that other susceptible species have not been discovered yet. Apart from farmed animals, stray cats and rodents have been identified as a potential opportunity for ongoing transmission in intense farming situations. Recognizing animal species that are most susceptible to infection is the first step in preventing ongoing transmission from humans. Minimizing the risk of zooanthraponosis requires multi-sectoral coordination that includes implementation of strict biosecurity measures such as controlled access to farms that house susceptible animals, bio-secure entry and exit protocols, disinfection protocols in farm, down time for animal transport vehicles and daily assessments of human handlers for exposure to SARS-CoV- 2. Hence, active surveillance in animal species that are prioritized based on risk assessment need to be initiated in coordination with health and environment sectors for early identification of emerging and re-emerging variants of SARS-CoV-2 virus in animals.
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Introduction/Aim: The spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enables it to recognise and bind host receptors. These dynamics have been modelled in various cell types and immortalised lines, but rarely in primary airway epithelial cells (AEC), and especially not in children. Therefore, this study on AEC recapitulated earlier work testing the hypothesis that exposure to the spike protein would induce airway immune responses in airway cells of young children. Method(s): Primary AEC monolayer cultures from healthy children (n = 5, <10 years old, males = 5) were exposed to the spike protein S1 subunit (0.01, 1, and 10 mug/mL) over 48 h. Induced inflammatory cytokines, interleukin (IL) 6 and IL8, and viral-associated chemokines, CCL5 and CXCL10 were measured via ELISA. Basal receptor gene expression (ACE2 and TMPRSS2) was measured in monolayer (n = 5) and terminally differentiated (air-liquid interface [ALI];n = 5) cell models as well as in ex-vivo cells obtained directly from nasal brushings (n = 71). Generalised linear modelling, accounting for individual variability, identified any statistical difference (p < 0.05). Result(s): Exposure to the spike protein resulted in no increase in IL6 and IL8 production, however a significant (p < 0.05) decrease was observed at the highest dose tested (10 mug/mL). CXCL10 was only significantly induced at the highest dose (10 mug/mL) whereas CCL5 was not induced. When compared to ex-vivo samples, baseline expression of ACE2 and TMPRSS2 was significantly lower in monolayer cultures (~57- and ~4- fold respectively, p < 0.05), whereas ALI cultures had similar expression levels. Conclusion(s): The use of recombinant spike protein and monolayer cultures appears to not accurately model SARS-CoV-2 spike protein-host interactions. The lack of inflammatory responses may be attributed to the lower receptor gene expression in monolayer cultures. Future studies should utilise live virus and ALI cultures as a more biologically relevant model to study virus-host interactions.
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RNA is a central molecule for the RNA virus life cycle as it functions not only as messenger for the synthesis of proteins, but also as storage of genetic information as genome. Given the central role of viral RNA in infection, it is expected that it must function as a hub for critical host-virus interactions. To test this, my laboratory has developed new approaches that have been applied to several viruses such as Sindbis virus, SARS-CoV-2 and human immunodeficiency virus (HIV).We have discovered a new universe of host-virus interactions with central regulatory roles in infection. Interestingly, these viruses, despite having different sequences and infection cycles, engage with a largely shared pool of cellular RNA-binding proteins. My laboratory is currently focused on understanding the regulatory mechanisms underpinning these master regulators with molecular detail. We envision that these central host-virus interactions are promising targets for broad-spectrum antiviral strategies. I am funded by an ERC Consolidator grant (vRNP-capture 101001634) and an MRC research grant (MR/R021562/1).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Atrial fibrillation (AF) is the most frequent form of cardiac arrhythmia in COVID-19 infected patients. The occurrence of AF paroxysms is often associated with the acute period of infection in time. At the same time, the pathophysiological mechanisms of the occurrence of AF associated with COVID-19 remain insufficiently studied. The review considers the available literature data on the influence of factors such as reduced availability of angiotensin-converting enzyme 2 receptors, interaction of the virus with the cluster of differentiation 147 and sialic acid, increased inflammatory signaling, "cytokine storm", direct viral damage to the endothelium, electrolyte and acid-alkaline balance in the acute phase of severe illness and increased sympathetic activity.Copyright © Autors 2023.
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Introduction Entry factors angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) facilitate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry into the host cells. Despite SARS-CoV-2s preference for respiratory system, extra-pulmonary organ involvement has been suggested. Recent studies report that SARS-CoV-2 leads to direct hepatic impairment in COVID-19 patients, necessitating further investigations about hepatic involvement. ACE2 and TMPRSS2 are expressed in primary human hepatocytes (PHH), suggesting a possible susceptibility to SARS-CoV-2. Despite this, data on infection and factors modulating functional regulation of SARS-CoV-2 infection in PHH are lacking. MicroRNAs (miRNAs) are approximately 22 nucleotide-long non-coding RNAs that have been shown to regulate various cellular processes including virus-host interactions. We aimed to study the susceptibility of PHH to SARS-CoV-2 and to evaluate the potential of miRNAs in modulating viral infection. Materials and methods We investigated the role of miRNAs to regulate SARS-CoV-2 infection in PHH in vitro. To strengthen our fndings, we analysed liver autopsies from COVID-19 patients. Results We demonstrate that PHH can be readily infected with SARS-CoV-2, resulting in robust replication and sustained host responses as indicated by the upregulation of several interferon-stimulated genes. In silico analyses unravelled miR-200c-3p, miR-429 and miR-141-3p as candidate miRNAs targeting ACE2 and, let-7c-5p targeting TMPRSS2. Expression of these miRNAs reduced SARS-CoV-2 infection in PHH. Furthermore, expression of several endogenous miRNAs was altered upon SARS-CoV-2 infection in PHH and human liver autopsies. Conclusion Our results show that PHH are susceptible towards SARS-CoV-2 and cellular miRNAs can diminish SARS-CoV-2 viral burden.
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The coronavirus disease 2019 (COVID-19) has recently spread worldwide due to the SARS-CoV-2 virus and has been declared a pandemic. A possible solution to prevent or restrict the spread of the COVID-19 pandemic is proposed in this article. Uncontrolled spread of the virus through breathing is a major concern. It is ideal if the entry of the virus inside the human body is re-stricted, as prevention is better than cure. Use of a "Smart-HELMET" that allows uncontaminated air (virus/bacteria/microbes-free) to breathe is proposed. The design of the Smart-HELMET, its working mechanism, the chemistry and biology of the virus-cell interaction inside a human body are discussed in detail. The proposed 'Smart-HELMET' prevents the spread of any respiratory illness through breathing. This is the need of the hour until a medicine/vaccine is made available in in vivo condition.Copyright © 2021 Bentham Science Publishers.
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2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019. 2019-nCoV has a zoonotic origin and poses a major threat to public health. However, little is known about the viral factors contributing to the high virulence of 2019-nCoV. Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors. Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection. In the past 17 years, the onset of 2019-nCoV, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV. This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-kappaB) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.Copyright © 2020 by the Chinese Medical Association.
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Organ-on-a-chip is a three-dimensional microfluidic system that simulates the cellular structure and biological milieu of an organ, that seemed to be constructed and studied substantially in the last decade. Microchips can be configured to suit disease states in a variety of organs, including the lung. When contrasted to traditional in vitro models like monolayer cell lineages, lung-on-a-chip models lays out a pragmatic portrayal of disease pathophysiology and pharmaceuticals' mode of action, and this is especially more prevailing in connection with the COVID-19 pandemic. Animal models have typically been used in pharmaceutical drug screening to assess pharmacological and toxicological reactions to a new entity. These adaptations, on the other hand, do not precisely represent biological reactions in humans. Present and prospective uses of the lung-on-a-chip model in the pulmonary system are highlighted in this overview. In addition, the constraints of existing in vitro systems for respiratory disease simulation and therapeutic discovery would be emphasized. Attributes of lung-on-a-chip transformative features in biomedical applications will be addressed to illustrate the relevance of this lung-on-chip model for medical science.Copyright © 2022
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The emerging new COVID 2019 pandemic, which started in 2019 in China (Wuhan) and is caused by SARS-CoV-2, raises critical concerns due to high morbidity and mortality. As many patients are infected and the numbers still increase, this may suggest that there are different variants of the virus and some of them are more pathogenic. Besides, the virus is suspected to have various evolutionary pathways since SARS-CoV-2 belongs to the RNA viruses' family, which is characterized by a high mutation rate. Additionally, it is crucial to understand the life cycle of the virus to be able to urge antiviral studies. Genotyping studies about viruses are also important in order to understand the transmission and evolution of the virus. The genome of SARS-CoV-2 has a furin-like cleavage site in its S protein that may affect its pathogenicity. It was found that insertions and deletions in S protein have an impact on the transmission and fusion of the virus. The single nucleotide polymorphisms (SNP) genotypes are used to track the relationship of virus isolates. Se-quence alignment revealed the presence of hundreds of inter-host mutations during person-to-per-son transmission. Furthermore, genetic recombination provided a second mechanism for virus evo-lution. In this review, we highlight the life cycle of the virus and methods of virus evolution caused by mutations or recombination of viral genomes.Copyright © 2021 Bentham Science Publishers.
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On December 31, 2019, the China Health Authority alerted WHO about 27 cases of pneumonia of unknown etiology in Wuhan City. It was subsequently named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and the disease as Coronavirus Disease 2019 (COVID-19). The disease has now become pandemic. Current review was done to summarize information on COVID-19 published in various scientific works. Electronic databases containing medical articles viz., MEDLINE/PubMed, Google Scholar etc were searched using the Medical Subject Headings 'COVID-19', '2019-nCoV', 'coronavirus' and 'SARS-CoV-2' during antecedent one year. All study designs were incorporated to harvest clinical, laboratory, imaging, and hospital course data. The intermediate host of the virus is still unknown. Respiratory droplets produced by the patient is main source of transmission. SARS-CoV-2 invades the airway epithelium by binding to angiotensin-converting enzyme-2 (ACE2) receptor with Coronavirus spike (S) protein. Most common symptoms are fever (98%), dry cough (77%), and dyspnea (63.5%). Later, complications like acute respiratory distress syndrome, septic shock etc may occur. Advanced age and co-morbidities like Diabetes have higher mortality otherwise Case Fatality Rate is 2-3%. RT-PCR is the diagnosis of choice. Since no universally accepted registered drug or FDA approved vaccine has come by now, prevention is the key. Hands should be regularly cleaned with soap or alcohol based sanitizer and in public, Nose and Mouth should be covered with face-mask and social distance of one meter should be maintained. While Vaccines are expected by early 2021, we should not forget to take comprehensive measures to prevent future outbreaks of zoonotic origin. Copyright © 2020, Kathmandu University. All rights reserved.
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Researches aimed at finding effective means of pathogenic therapy for this viral infection are extremely relevant. Researches of the last three years have established that some human pathogenic coronaviruses - MERS, SARS-CoV and SARS-CoV-2, contain aliphatic polyamines in their structure, which participate in the packaging of genetic material (DNA, RNA), as well as the nucleocapsid. Virus-host cell interactions also provide adhesion processes on the surface of the cytoplasmic membrane of target cells. In the intra-cellular space, aliphatic polyamines actively affect the translation and replication processes of the genetic material and necessary proteins of the virus itself, as well as the formation of daughter viruses. Long-term persistence in the SARS-CoV-2 infected organism is largely due to the absorption of polyamines by corona-virus localized in target cells of the blood and parenchymatous organs. Unfortunately, the above new facts did not serve as a prerequisite for finding effective means of pathogenetic therapy for COVID-19, based on the inhibition of polyamine-dependent processes that ensure long-term persistence of SARS-CoV-2 in the infected organism. We are talking about specific drugs such as alpha-difluoromethylornithine and its ana-logues, which are successfully used in oncology in the complex treatment of malignant neoplasms with the aim of lowering the level of aliphatic polyamines in the affected areas of malignantly transformed organs. We recommend the use of polyamine-free and polyamine-deficient diets for COVID-19 for the first time. In the planned study, we will present tables with food products of animal and vegetable origin, characterized by extremely low content and/or absence of aliphatic polyamines in them. At the same time, food products with a high content of aliphatic polyamines should be excluded from the general list of products recommended for COVID-19 patients. We also recommend the use of a polyamine-deficient diet (with a preventive purpose) during the COVID-19 pandemic to a wide contingent of practically healthy individuals, convalescents, medical staff of specialized infectious disease clinics, as well as family members of SARS-CoV-2 infected patients. Copyright © 2022, Yerevan State Medical University. All rights reserved.
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Interactions of platelets with circulating cells and vessel walls are implicated in various inflammatory processes. In certain circumstances, the hemostatic and inflammatory functions of platelets may overlap. Platelet-lymphocyte/leukocyte interactions can effectively regulate chronic inflammatory conditions. Platelet extracellular vesicles play a prominent role in thrombosis. In this review, we provide an overview of the molecules associated with platelet-cell interaction and the role of platelet extracellular vesicles in cardiovascular disorders and coronavirus disease 2019, which has posed a significant threat to global health due to infection with severe acute respiratory syndrome coronavirus 2. In addition to recruiting leukocytes to resolve inflammation associated with inflammatory diseases, such as coronavirus disease 2019, nutrients may also play a significant role in human metabolism.
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Purpose: The field of osteoarthritis (OA) biology is rapidly evolving and brilliant progress has been made this year as well. Methods: Landmark studies of OA biology published in 2021 and early 2022 were selected through PubMed searches and classified by their molecular mechanisms, and it was largely divided into the intra-cellular mechanisms and the inter-compartment or inter-cellular interaction in OA progression. Results: The intra-cellular mechanisms involving OA progression included 1) Piezo1/TRPV4-mediated calcium signaling, 2) low grade inflammation by TLR-CD14-LBP complex and IKKβ-NFkB signaling, 3) PGRN/TNFR2/14-3-3ε/Elk-1 anabolic cascade, 4) G protein-coupled receptor (GPCR) signaling, 5) mechanical loading-cilia/Ift88-hedgehog signaling, 6) mitochondrial fission by ERK1/2-DRP1 pathway, and 7) hypoxia-DOT1L-H3K79 methylation pathway. The studies on inter-compartment or inter-cellular interaction in OA progression included the following subjects: 1) the anabolic role of Lubricin, a proteoglycan from superficial zone cells, 2) osteoclast-chondrocyte interaction via exosomal miRNA and sphingosine 1-phosphate (S1P), 3) αV integrin-mediated TGFβ activation by mechanical loading, 4) TGFβ-mediated suppression of sclerostin in osteocytes, 5) catabolic role of Flightless I as a DAMPs-triggering molecule, and 6) catabolic role of paracrine signaling from fat. Conclusions: Despite the disastrous Covid-19 pandemic situation, many outstanding studies have expanded the boundary of OA biology. They give us not only critical insight on pathophysiology, but also clue for the treatment of OA.