Dissertations / Theses: 'SARS-CoV-2'

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Daff, Kaitlyn M. "Nutritional Implications in SARS-CoV-2." Youngstown State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1596622611336371.

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Condé, Lionel. "Contrôle traductionnel du SARS-CoV-2." Electronic Thesis or Diss., Lyon, École normale supérieure, 2024. http://www.theses.fr/2024ENSL0010.

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Endant l’infection virale, la régulation de l’expression des gènes est au cœur des interactions complexes entre l'hôte et le pathogène. Les virus exploitent la machinerie cellulaire de l'hôte pour assurer la synthèse de leurs protéines nécessaires pour la réplication et la propagation de l'infection. C'est notamment le cas lors de l'infection par le SARS-CoV-2, qui induit rapidement une inhibition globale de la traduction cellulaire grâce à l'action de facteurs viraux tels que la protéine Nsp1. Pour produire efficacement ses protéines, le virus doit alors mettre en place des stratégies pour contourner cette inhibition. Le génome du SARS-CoV-2 s'exprime à partir de 10 ARN, l'ARN génomique (ARNg) et 9 ARN sous-génomiques qui possèdent une région leader commune mais des régions 5'UTR uniques pour chacun des transcrits. Mon travail s'est concentré sur les éléments structuraux qui régulent la traduction des différents ARN du SARS-CoV-2.À travers un ensemble d’expériences in vitro (lysat de réticulocytes) et en cellules, nous avons découvert que l’efficacité de traduction variait significativement entre les différents ARN viraux. En particulier, l'ARN génomique, malgré sa structure complexe, se distingue par une efficacité de traduction particulièrement élevée. Nous avons aussi déterminé que la structure tige-boucle SL1, présente dans l’ensemble des transcrits viraux, était un déterminant majeur pour l'expression des ARN et qu'elle jouait également un rôle crucial pour contrer l'inhibition induite par la protéine virale Nsp1. Nous avons établi que l'initiation de la traduction se déroulait par un mécanisme dépendant de la coiffe et nécessitait le complexe eIF4F. Enfin notre étude a également permis de caractériser le rôle de deux courtes phases de lecture ouvertes (uORF) retrouvées dans certaines régions 5'UTR des ARN du SARS-CoV-2; ces uORFs ont des impacts variables selon leur position
During viral infection, the regulation of gene expression is central to the complex interactions between the host and the pathogen. Viruses exploit the host's cellular machinery to ensure the synthesis of their proteins, which are necessary for replication and the spread of the infection. This is particularly the case with SARS-CoV-2 infection, which rapidly induces a global inhibition of cellular translation through the action of viral factors such as the Nsp1 protein. To efficiently produce its proteins, the virus must implement strategies to bypass this inhibition. The SARS-CoV-2 genome is expressed from 10 RNAs, the genomic RNA (gRNA) and 9 subgenomic RNAs that possess a common leader region but unique 5'UTR regions for each of the transcripts. My work focused on the structural elements that regulate the translation of the different SARS-CoV-2 RNAs.Through a series of in vitro (reticulocyte lysate) and in-cell experiments, we discovered that the translation efficiency varied significantly among the different viral RNAs. In particular, the genomic RNA, despite its complex structure, distinguishes itself by its remarkably high translation efficiency. We also determined that the SL1 stem-loop structure, present in all viral transcripts, was a major determinant for RNA expression and also played a crucial role in countering the inhibition induced by the Nsp1 viral protein. We established that translation initiation occurred through a cap-dependent mechanism and required the eIF4F complex. Finally, our study also characterized the role of two short upstream open reading frames (uORFs) found in certain 5'UTR regions of SARS-CoV-2 RNAs; these uORFs have variable impacts depending on their position

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Dafalla, Israa Yahia Al Hag Ibrahim. "Improving SARS-CoV-2 analyses from wastewater." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-20237.

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Wastewater-based epidemiology (WBE) analyzes wastewater for the presence of biological and chemical substances to make public health conclusions. COVID-19 disease is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that infected individuals shed also in their feces, making WBE an alternative way to track SARS-CoV-2 in populations. There are many limitations to the detection and quantification of SARS-CoV-2 from wastewater, such as sample quality, storage conditions or viral concentration. This thesis aims to determine the extent of these limitations and the factors that contribute to them. Other viruses can help the measurements for example Bovine coronavirus (BCoV) can be spiked as a process surrogate, while Pepper mild mottle virus (PMMoV), a fecal biomarker is used to estimate the prevalence of SARS-CoV-2 infection. This study involved two distinct wastewater samples. For method comparison both samples were processed with two methods: virus concentration by electronegative (EN) filtration or direct RNA extraction method. From the RNA extracts RT-qPCR assays were performed to identify and quantify SARS-CoV-2, BCoV, and PMMoV. Based on the obtained cycle threshold (Ct) values, viral gene copy numbers and virus concentration of the original wastewater samples were calculated. Statistical tests were conducted to assess suggested hypothesizes and variations within the data. Results revealed differences in viral contents due to different sample qualities and as a result of freezing and thawing. Furthermore, different sample processing methods led to differences in quantification. In conclusion, improving analysis of SARS-CoV-2 in wastewater using methodologies with better detection efficiency leads to more reliable results.

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Vareschi, Rodolfo Dimitrius. "Cloud computing adoption during SARS-COV-2 pamdemic." Master's thesis, Instituto Superior de Economia e Gestão, 2021. http://hdl.handle.net/10400.5/21746.

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Mestrado em Gestão de Sistemas de Informação
Due to the rapid global spread of the pandemic caused by the new coronavirus, companies and institutions were forced to take precautionary measures to reduce the risk of contagion, such as asking employees to work remotely from their homes. In this scenario, cloud computing technology has proven to be a great ally of companies to overcome the crisis caused by the pandemic.The adoption of Cloud Computing technology has accelerated in recent years and, according to a forecast made by the International Data Corporation (IDC), investment in cloud services will exceed US $ 1.0 trillion in 2024, which represents a rate of annual growth of 15.7% (Villars et al., 2020).In an attempt to help organizations plan their strategies for adopting cloud computing, the present study intends to contribute to the existing literature on the subject, aiming to identify the main factors that influence the adoption of such technology during the Covid-19 pandemic crises.For this purpose, 18 factors identified during the literature review and were presented to 11 experts in the field of cloud computing technology, in order to seek a consensus regarding the order of importance of these factors.Through the Delphi method, divided into two phases and with two rounds, a list was obtained, ordered according to the degree of importance of the main factors that influence the adoption of cloud computing. After analyzing the data, the results obtained show that the six most important factors are: (1) Adoption, Migration and Acquisition Cost; (2) Availability and Accessibility; (3) Scalability; (4) Cost of Data Confidentiality and Availability Loss; (5) Security and (6) Customization.
Devido à rápida disseminação global da pandemia causada pelo novo coronavírus, empresas e instituições foram forçadas a tomar medidas de precaução para reduzir o risco de contágio, como pedir aos funcionários que trabalhassem remotamente das suas casas. Nesse cenário, a tecnologia de computação em nuvem tem se mostrado uma grande aliada das empresas para superar a crise provocada pela pandemia.A adoção de Computação em Nuvem tem se acelerado nos últimos anos e, segundo previsão da International Data Corporation (IDC), os investimentos em serviços em nuvem ultrapassarão US $ 1,0 milhão de bilhões em 2024, o que representa uma taxa de crescimento anual de 15,7% (Villars et al., 2020).Na tentativa de auxiliar as organizações no planeamento das suas estratégias de adoção da computação em nuvem, o presente estudo pretende contribuir com a literatura existente sobre o assunto, e tem como objetivo de identificar os principais fatores que influenciam a adoção dessa tecnologia durante a crise pandêmicas de Covid-19.Nesse sentido, 18 fatores identificados durante a revisão da literatura foram apresentados a 11 especialistas na área de tecnologia de computação em nuvem, a fim de encontrar um consenso quanto à ordem de importância desses fatores.Através do método Delphi, dividido em duas fases e com duas rondas, foi obtida uma lista ordenada de acordo com o grau de importância dos principais fatores que influenciam a adoção da computação em nuvem. Após a análise dos dados, os resultados obtidos mostram que os seis fatores mais importantes são: (1) Custo de Adoção, Migração e Aquisição; (2) Disponibilidade e acessibilidade; (3) Escalabilidade; (4) Custo de perda de confidencialidade e disponibilidade de dados; (5) Segurança e (6) Personalização.
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Колюбакіна, Л. В., О. В. Власова, and Н. М. Крецу. "Kлініко-параклінічні особливості SARS-Cov-2 у новонароджених." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18391.

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Elfström, Mia. "Synthesis of SARS-CoV-2 Main Protease Inhibitors." Thesis, Uppsala universitet, Läkemedelsdesign och läkemedelsutveckling, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-449953.

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Coronaviruses have been responsible for several global disease outbreaks over the last 20 years, including the “Severe Acute Respiratory Syndrome” in 2002/2003, the “Middle East Respiratory Syndrome” in 2012, and the “Coronavirus Disease of 2019 (COVID19)”. These viruses are highly contagious and can cause multiple medical disorders upon contraction, such as common cold or lower respiratory infections. SARS-CoV-2, the newly emerged coronavirus variant of 2019, has been confirmed as the cause of the ongoing COVID19 pandemic, which infected over 167 million people worldwide and, by the end of May 2021, has a death toll of over 3 million people. Even though several SARS-CoV-2 vaccines have made it to the market, no proven options have yet been discovered for treating COVID19 infections. The aim of this project is, therefore, to improve the potency of two active SARS-CoV-2 main protease (Mpro) inhibitors (ML188 and X77) by performing a structure-activity-relationship study where two specific sites of the inhibitors are altered. The inhibition activity of these compounds is then tested on isolated SARS-CoV-2 Mpro. The four-component Ugi reaction was utilized to synthesize the ML188 and X77 analogs, which were purified by column chromatography before testing. During this project, six pure analogs were successfully synthesized and will be sent shortly for testing. Inhibitors with good activity against SARS-CoV-2 Mpro will be further tested for their antiviral activity in cell-based infection assays. The results obtained from this study will later be used to perform a second structure-activity-relationship study to further improve the potency of the two inhibitors by developing a 2nd generation library.

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Bălan, Mirela. "Integrative bioinformatic analysis of SARs-CoV-2 data." Thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-450821.

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Bui, Xuan Klaudia. "Biosensori FET per il rilevamento del SARS-CoV-2." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2020.

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Nel 2020 la presenza del SARS-CoV-2 ha indotto alla produzione e miglioramento dei metodi per la rilevazione del virus. Negli ospedali di Wuhan vari campionatori d'aria sono stati utilizzati per verificare la presenza e la diffusione del virus. Il campione così raccolto viene analizzato tramite la reazione a catena della polimerasi (PCR). Lo svantaggio principale di questa reazione è il tempo richiesto per la diagnosi che è di tre ore. Per questo motivo sono stati effettuati vari studi di ricerca per trovare un metodo più rapido ma sempre efficace. Quindi vengono proposte le ultime scoperte convalidate per la determinazione del SARS-CoV-2. In particolare, i candidati migliori vengono rappresentati dai biosensori, dispositivi veloci e altamente sensibili che usano i biorecettori per creare il legame con la cellula bersaglio. Il documento presenta una dettagliata analisi del funzionamento del transistor ad effetto campo rivestito di un film di grafene su cui vengono posizionati gli anticorpi del virus. Come mostrato nell'elaborato, questo è un ottimo dispositivo per un rapido rilevamento del virus in quanto in tempo reale fornisce l'esito, positivo o negativo, dei tamponi nasofaringei.

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Flygare, Agnes. "The synthesis of main protease inhibitorsagainst SARS-CoV-2." Thesis, Uppsala universitet, Preparativ läkemedelskemi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-448451.

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Fignani, Daniela. "Bidirectional relationship between SARS-CoV-2 and Diabetes Mellitus." Doctoral thesis, Università di Siena, 2023. https://hdl.handle.net/11365/1224916.

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Several studies demonstrated that COVID-19 has a more severe outcome in patients with diabetes; in addition, in normoglycemic patients, the infection can alter glycometabolic control increasing the risk to develop Type 2 Diabetes (T2D) or dysglycaemia. Thus, a bidirectional relationship between COVID-19 and diabetes can be hypothesized but a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Increasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2) is a necessary step for SARS-CoV-2 infection permissiveness. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyze ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies. Using multiple reagents and antibodies, we showed that ACE2 is expressed in human pancreatic islets, where it is preferentially expressed in subsets of insulin producing β-cells. ACE2 is also highly expressed in pancreas microvasculature pericytes and moderately expressed in rare scattered ductal cells. Moreover, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, increase ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets. Finally, we demonstrated that ACE2 expression is increased in pancreatic islets of T2D donors in comparison to non-diabetic controls alongside with a higher colocalization rate between ACE2 and insulin using both anti-ACE2 antibodies. Of note, a higher frequency of peri-islets macrophages was detected in T2D donors respect to non-diabetic. Upregulation of ACE2 was demonstrated in pancreatic islet β-cells of T2D donors. Higher ACE2 expression in T2D islets might increase their susceptibility to SARS-CoV-2 infection during COVID-19 disease in T2D patients, thus exacerbating glycometabolic outcomes and worsening the severity of the disease. Taken together, our data indicate a potential link between SARS-CoV-2 and diabetes.

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Pisil, Yalcin. "The Study on Neutralization of Human Immunodeficiency Virus and SARS CoV-2 - Neutralization Resistance of SHIV and Neutralization Assay for SARS CoV-2 -." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/264673.

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京都大学
新制・課程博士
博士(人間・環境学)
甲第23392号
人博第1005号
新制||人||237(附属図書館)
京都大学大学院人間・環境学研究科相関環境学専攻
(主査)准教授三浦智行, 教授川本卓男, 准教授西川完途
学位規則第4条第1項該当
Doctor of Human and Environmental Studies
Kyoto University
DFAM

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Phan, Alexandra. "Identification of MMP-9 as a Driving Factor in SARS-CoV-2 Entry." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42771.

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Since its emergence in December 2019, SARS-CoV-2 has infected over 200 million people globally. SARS-CoV-2 spike (S) decorates the viral envelope and is responsible for facilitating viral entry into the host cell. To mediate membrane fusion, S must be proteolytically cleaved. For the closely related SARS-CoV S, cleavage at the host cell surface must be facilitated by the serine protease TMPRSS2. We demonstrated that SARS-CoV-2 S can facilitate fusion independent of TMPRSS2 and sought to identify other proteases capable of driving SARS-CoV-2 S-mediated fusion. We show that the ADAMs and MMP inhibitor GI 254023X is capable of substantially reducing SARS-CoV-2 S-mediated syncytium formation. Additionally, we identified MMP-9, a protein target of GI 254023X, as a host protease capable of enhancing SARS-CoV-2 lentivirus entry in HEK293T-ACE2 cells. These results implicate ADAM and MMP proteases, in particular MMP-9, as potential antiviral drug targets against COVID-19 pathogenesis.

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Жукова, А. Ю. "Екологічні фактори та умови виникнення пандемії вірусу SARS-CoV-2." Master's thesis, Сумський державний університет, 2020. https://essuir.sumdu.edu.ua/handle/123456789/81542.

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Поширення коронавірусної хвороби 2019 в Україні зафіксовано 3 березня 2020 року, коли підтвердився перший випадок хвороби в Чернівецькій області. За даними МОЗ та РНБО станом на ранок 29 листопада 2020 року в Україні підтверджено 722 679 випад-ків зараження SARS-CoV-2, з них 12 213 осіб померли, 339 378 одужали. Так, станом на кінець листопада Україна посідала 17 місце у світі (9-е в Європі) за кількістю зафіксованих випадків інфікування і 22-е у світі за кіль-кістю померлих. Кількість інфікованих на 1 мільйон населення складає 16566 осіб (61-е місці у світі і 31-е в Європі), а кількість померлих з COVID-19 на мільйон населення — 280 осіб (54-е місце у світі і 29-е в Європі). Саме пандемічний характер розповсюдження цього вірусу, відносно висока його ле-тальність визначилои актуальність дослідження. Мета та завдання дослідження: дослідження характеру пандемії, можливих джерел походження, ознайомитися із світовим досвідом боротьби з коронавірусною інфекцією та проаналізувати поточну ситуацію в Сумській області та м. Суми.

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Beneš, Martin. "HMM modelling for the spread of the SARS–CoV–2." Thesis, Linköpings universitet, Statistik och maskininlärning, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176735.

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The aim of the project is to develop an HMM for the current spread of the SARS–CoV–2 virus. The HMM could be coupled with a SIR+ based compartmental model for the different types of statistics — confirmed cases, hospitalizations, deaths. The confirmed cases should be treated as a random sample from the whole population of infected and the probability of sampling should try to take into account the different testing strategies. The aim of the project would be to compare the spread of the virus in different countries (e.g. Czech Republic, Poland, Sweden, Italy, but other depending on the availability of data are possible) through regional (whenever possible) dynamics. For the thesis publicly available COVID–19 connected data will be used.

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Courjon, Johan. "Activation de l’inflammasome NLRP3 au cours des bactériémies à E. coli ou S. aureus et durant l’infection à SARS-CoV-2." Electronic Thesis or Diss., Université Côte d'Azur, 2021. http://www.theses.fr/2021COAZ6009.

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A la phase précoce d’une infection bactérienne ou virale l’immunité innée est capable de détecter certains motifs microbiens conservés (PAMP) reconnus par des récepteurs dédiés à ces motifs (PRR) permettant ainsi d’amorcer la réaction pro-inflammatoire via différentes voies de signalisation. Les inflammasomes représentent une catégorie de PRR capable de transformer la pro-IL-1β et la pro-IL-18 en cytokines pro-inflammatoires actives ainsi que d’induire une mort cellulaire pro-inflammatoire nommée pyroptose. NLRP3 est l’inflammasome le plus étudié. De nombreuses bactéries et de nombreux virus ont été décrits comme pouvant soit activer soit inhiber l’inflammasome NLRP3 mais l’implication clinique de cette activation ou inhibition, reste pour le moment indéterminée. L’objectif de ma thèse était d’étudier l’implication de l’inflammasome NLRP3 au cours de la bactériémie chez l’homme. L’apparition de l’épidémie de COVID-19 nous a permis d’élargir cette étude à l’infection par le SARS-CoV-2. Le protocole NLRP3-BACT nous a permis de mettre en œuvre un test cellulaire à partir du sang total afin d’évaluer le niveau d’activation de la Caspase-1 dans les monocytes et polynucléaires neutrophiles (PNN) ainsi que le potentiel d’activation de l’inflammasome NLRP3 dans ces cellules chez des patients présentant une bactériémie à S. aureus ou E. coli via une analyse par cytométrie en flux (signal FAM-FLICA).Le protocole CoVinnate avait pour objectif l’utilisation du test cellulaire précédemment mentionné afin de décrire l’activation d’une partie du système immunitaire inné dans les différentes cellules myéloïdes circulantes des patients COVID-19 ainsi que l’évaluation de ce test en tant qu’outil pronostique.Pour NLRP3-BACT 22 patients ont été inclus depuis le début de de l’étude, 16 ont bénéficié d’une analyse cytométrique. Dans cette première série de patients inclus nous avons mis en évidence que les monocytes présentent un potentiel d’activation de la Caspase-1 par Nigéricine+LPS plus important que les donneurs sains. Par ailleurs, l’activation basale de cette caspase dans les monocytes est plus importante chez les patients de réanimation et ceux infectés par E. coli. Enfin la multiplication de la MFI du signal FAM-FLICA induite par Nigéricine+LPS est plus important pour les patients de médecine comparativement aux patients de réanimation.Pour CoVinnate, 66 patients COVID-19 et 24 donneurs sains ont été inclus durant la période de l’étude. Dans les cellules CD66b+ CD16dim nous avons observé une diminution significative du signal de la sonde FAM-FLICA chez les patients les plus sévères comparativement aux témoins. Au sein des granulocytes, l’activation de la Caspase-1 induite par la Nigéricine était altérée dans les granulocytes CD66b+ CD16dim selon le degré de sévérité des patients. Nous avons enregistré une augmentation de l’activation de NLRP3 induite par la Nigéricine dans les monocytes non-classiques isolés chez les patients les plus graves, cet effet était inversement corrélé au nombre total de monocytes non-classiques. Chez les patients les plus sévères on notait une augmentation du nombre de cellules CD66b+CD16dimCD15+CD10- correspondant à des neutrophiles immatures. Nous avons utilisé la diminution des monocytes non-classiques et le défaut d’activation de NLRP3 par la Nigéricine des granulocytes CD66b+ CD16dim pour construire un score pronostique. Nous avons mis en évidence une corrélation entre ce score et le rapport SpO2 / FiO2 le jour de l’inclusion ainsi que 48 heures plus tard. Nous avons également constaté une association significative de ces deux marqueurs avec l’évolution finale des patients. Mon travail a permis de mieux comprendre l’implication de l’inflammasome NLRP3 chez l’homme au cours de la bactériémie et durant l’infection à SARS-CoV-2. Nous envisageons d’utiliser ces travaux pour caractériser la réponse des patients aux traitements immunomodulateurs utilisés dans la COVID-19 notamment les corticoïdes
At the early phase of bacterial or viral infections, innate immunity is able to detect some conserved microbial motifs (PAMP) recognized by receptors dedicated to these motifs (PRR), thus making it possible to initiate the pro-inflammatory reaction via different signaling pathways. Inflammasomes represent a family of PRR able to transform pro-IL-1β and pro-IL-18 into active pro-inflammatory cytokines as well as inducing a pro-inflammatory cell death called pyroptosis. NLRP3 is the most studied inflammasome. Many bacteria and viruses have been described as being able to either activate or inhibit the NLRP3 inflammasome, but the clinical implication of this activation or inhibition, under the control of a particular microorganism, remains undetermined at this time.The objective of my thesis was to study the involvement of the NLRP3 inflammasome during bacteremia in humans. The onset of the COVID-19 epidemic allowed us to expand this study to SARS-CoV-2 infection.The NLRP3-BACT protocol allowed us to implement a cellular test performed on whole blood to assess the level of Caspase-1 activation in monocytes and polymorphonuclear neutrophils (PMN) as well as the activation potential of the NLRP3 inflammasome in these cells in patients with S. aureus or E. coli bacteremia via flow cytometry (fluorescent inhibitor probe, FAM-FLICA).The objective of the CoVinnate protocol was to use the aforementioned cellular test to describe the activation of a part of the innate immune system in the various circulating myeloid cells of COVID-19 patients as well as the evaluation of this test as a prognostic tool.For NLRP3-BACT 22 patients have been included since the start of the study, 16 have undergone cytometric analysis. In this first series of patients included, we demonstrated that monocytes have a greater potential for Caspase-1 activation by Nigericin+LPS than healthy donors. In addition, basal activation of this caspase in monocytes is greater in intensive care patients and in those infected with E. coli compared to the ID ward and S. aureus respectively. Finally, the multiplication of the MFI of the FAM-FLICA signal induced by Nigericin + LPS is more important for medical patients compared to intensive care patients.For CoVinnate, 66 COVID-19 patients and 24 healthy donors were included during the study period. In CD66b+ CD16dim cells, we observed a significant decrease of the FAM-FLICA probe signal in the most severe patients compared to the controls. Within granulocytes, the activation of Caspase-1 induced by Nigericin was decreased in CD66b+ CD16dim cells according to the severity of the patients. We recorded an increase in Nigericin-induced activation of NLRP3 in non-classical monocytes isolated from the most severe patients, this effect was inversely correlated with the total number of non-classical monocytes. In the most severe patients there was an increase in the number of CD66b+CD16dimCD15+CD10- cells corresponding to immature neutrophils.We used the decreased number in non-classical monocytes and the failure of NLRP3 activation upon nigericin activation in CD66b + CD16dim granulocytes to build a prognostic score. We found a correlation between this score and the SpO2 / FiO2 ratio on the day of inclusion as well as 48 hours later. We also found a significant association of these two markers with the final outcome of the patients.My work has led to a better understanding of the involvement of the NLRP3 inflammasome in humans during bacteremia and during SARS-CoV-2 infection. We plan to use this work to characterize the response of patients to immunomodulatory treatments used in COVID-19, including corticosteroids

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Малкович, Н. М. "Прогнозування ризику розвитку середньотяжкого та тяжкого перебігу інфекції SARS-CoV-2." Thesis, БДМУ, 2022. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19591.

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Chekkala, Vivekanand Aashlesha. "Statistical Analysis of SARS-CoV-2 in wastewater streams in Stockholm." Thesis, KTH, Kemiteknik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-298383.

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Avloppsvattenbaserad epidemiologi är ett framåtväxande område som används för att bedöma förekomsten av virala belastningar i avloppsvatten och på så sätt bidra med trender av virusbildning. I denna studie har avloppsvattenbaserad epidemiologi utnyttjats för att bedöma förekomsten av severe acute respitory syndrome coronavirus 2 (SARS-CoV-2) i avloppsvatten med mål att tidigt upptäcka viruset. Det är känt att parametrarna i avloppsvatten påverkar detektionen av SARS-CoV-2 i stickprov tagna från olika regioner i Stockholm. I denna studie har flödet (m3 /dag) och den kritiska gränsen av Pepper mild mottle cirus (PMMoV) utsetts som oberoende variabler, och genkopieringsnumret av SARS-CoV-2 per m3 av obehandlat avloppsvatten utsetts till den beroende variabeln. Studiens mål riktar sig till att genomföra statistiska tester för att få förståelse av hur variablerna fördelar sig genom att utnyttja gaussian studier. Sambandet mellan de oberoende och beroende variablerna noterades av icke-parametriska tester och korrelationsstudier. Värdena modellerades i en regressionsanalys samt att en prognosmodell skapades genom att utnyttja ARIMA modellen.
Wastewater Based Epidemiology (WBE) is an emerging area to assess the presence of viral loads in wastewater streams and thereby provide trends about the emerging viruses. In this study, Wastewater Based Epidemiology is used to assess the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the wastewater streams, possibly providing for early detection. It is known that wastewater parameters effect the detection of SARS-CoV-2 in the wastewater samples collected from different regions of Stockholm. In our study, flowrate (m3/day) and Critical Threshold (Ct) value of Pepper mild mottle virus (PMMoV) are the independent variables selected when the gene copy number of SARS-CoV-2 /m3 of raw wastewater is the dependent variable. The aim of the study is to perform a series of statistical tests to understand the distribution of the variables using gaussian studies, the relationship between the independent and the dependent variables is noted by non-parametric tests and correlation studies. The data is modeled using regression analysis and forecasting model is created using an ARIMA model.

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Gruvnäs, Amanda. "Avloppsvattenbaserad epidemiologi med fokus på SARS-CoV-2 : Analys inom Västerås kommun." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451696.

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Globalt har hela världens befolkning påverkats både ekonomiskt och psykiskt av coronaviruset SARS-CoV-2, som har drabbat så många människor med covid-19 att det klassas som en pandemi. Strax efter pandemins utbrott upptäcktes det att viruset utsöndras från avföring och ut i spillvattennätet som leder till reningsverken. Då virusmängden ökar i avloppsvattnet ökar även covid-19 fallen i samhället. Ökning av virusmängd i avloppsvatten kan nämligen signalera om att det förekommer smittspridning i samhället. Avloppsvattenbaserad övervakning kan dock användas som komplement till andra teststrategier vilket EU-kommissionen har nämnt i en rekommendation. Trender kan analyseras för att i ett tidigt skede informera sjukvård och regioner om ökad smittspridning. På Kungsängens reningsverk i Västerås kommun har Mälarenergi analyserat avloppsvattnet för att ta reda på om ökning av virus i avloppsvatten kan indikera på ökad smittspridning i Västerås kommun. De har samlat in proverna och skickat det till SGS Analytics AB Sweden som har analyserat proverna med RT-qPCR. CT-värdena har normaliserats med vattenflöden. Korrelationstest har gjorts mellan virusmängd i avloppsvattnet och covid-19 fall, dödsfall samt IVA-fall. Det fanns ett signifikant svagt negativt samband mellan virusmängd i avloppsvatten och covid-19 fall per vecka. Mellan virusmängd och IVA-fall eller dödsfall fanns inget samband. Det finns en del felkällor som kan ha påverkat virusmängden. Vid höga vattenflöden kan PCR inhibitorer från tillskottsvatten och lakvatten ha påverkat CT-värdena. Värdena är höga på sommaren trots att covid-19 fall, dödsfall och IVA-fall var som lägst. Inhibitorer skapar direkt eller indirekt högre CT-värden vilket tolkas som lägre virusmängder.

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Granholm, Nicolai, and Eric Tjärnström. "Metagenomic Classification using Machine Learning : Applied to SARS-CoV-2 and Viruses." Thesis, Umeå universitet, Institutionen för matematik och matematisk statistik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-172008.

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The use of machine learning within the field of metagenomic classification is becoming more relevant since the increasing sequencing speed demands faster and more accurate classification algorithms. This thesis explores the possible application of machine learning methods, used individually and in an ensemble solution, for binary classification of short DNA sequences. The models Convolutional Neural Network, Recurrent Neural Network, Support Vector Machine, Random Forest, Gradient Boosting and K-Nearest Neighbour are trained to distinguish viruses and SARS-CoV-2 from other organisms. The models are evaluated on generated data, as well as real samples. The outcome of this thesis show that machine learning methods have satisfying results when classifying short DNA sequences, in terms of both accuracy and speed. The best overall accuracies are obtained using ensemble solutions consisting of several machine learning models.
Användningen av maskininlärning inom metagenomisk klassificering är ett område som blir mer och mer relevant på grund av att den ökade sekvenseringshastigheten ställer större krav på snabbare och precisare klassificeringsalgoritmer. Detta examensarbete utforskar möjligheten av att använda maskininlärningmodeller, både individuellt och kombinerat, för binär klassificering av av korta DNA sekvenser. Modellerna Convolutional Neural Network, Recurrent Neural Network, Support Vector Machine, Random Forest, Gradient Boosting and K-Nearest Neighbour är tränade till att kunna skilja på virus och SARS-CoV-2 från andra organismer. Modellerna är utvärderade på genererad, samt verklig data. Slutsatsen av detta examensarbete visar att maskininlärningsmetoder har ett tillfredsställande resultat vid klassificeringen av korta DNA sekvenser, både i träffsäkerhet och tidsomfång. De bästa träffsäkerheterna kommer från kombinerade lösningar bestående av flera maskininlärningsmodeller.

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GRIMALDI, ANTONIO. "AN IMPROVED GENOMIC SURVEILLANCE APPROACH TO DISSECT THE SARS-COV-2 PANDEMIC." Doctoral thesis, Università degli Studi di Milano, 2022. https://hdl.handle.net/2434/946458.

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Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only approach to rapidly monitor and tackle emerging variants of concern (VOC) of the COVID-19 pandemic. Such scrutiny is crucial to limit the spread of VOC that might escape the immune protection conferred by vaccination strategies. It is also becoming clear now that efficient genomic surveillance would require monitoring the host gene expression to identify prognostic biomarkers of efficacy and disease progression. Here we applied an integrated workflow for RNA extracted from nasal swabs to obtain in parallel the entire genome of SARS-CoV-2 and host respiratory epithelium transcriptome, representing the majority of Italian processed genomic samples. In addition, we have matured and applied novel proof-of-principle approaches to prioritize possible gain-of-function mutations by leveraging patients' metadata and isolated patient-specific signatures of SARS-CoV-2 infection. The goals mentioned above have all been achieved in a cost-effective manner that does not require automation, in an effort to allow any lab with a benchtop sequencer and a limited budget to perform integrated genomic surveillance on premises.

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CIMINO, Anna Rita. "Amphiphilic and ganglioside-binding properties of SARS CoV-2 Spike protein variants dissected by charge shift electrophoresis in deterged solution." Doctoral thesis, Università degli studi del Molise, 2022. https://hdl.handle.net/11695/115828.

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The data contained in this thesis provide a demonstration of the amphiphilic properties of SARS-2-S, the Spike glycoprotein of SARS-CoV-2, as well as of its  (B.1.617.2, delta) and  (B.1.1.529, omicron) variants, obtained by charge shift electrophoresis (CSE) in detergent solution. Wild-type,  and  SARS-2-S presented distinct amphiphilic properties, reflecting their ability to participate in the formation of mixed TX-100/DOC and TX-100/CTAB micelles of homogeneous size. The SARS-2-S  plus variant exhibited a more limited amphiphilicity in TX/DOC, possibly reflecting its propensity for TX-100/DOC micelles with a lower DOC content, perhaps due to charge-specific interactions between DOC and positively charged amino acids. We also provide a demonstration of the ability of different variants of the SARS-CoV-2 Spike glycoprotein to bind GM1 ganglioside, by the same approach, in the absence of detergents. Even though the sialoside-binding ability of coronaviruses was known, ours is the first direct demonstration of the GM1-ganglioside-binding ability of the SARS-2-S glycoprotein. Unlike wild-type SARS-2-S and the SARS-2-S  variant, the SARS-2-S  and  plus variants exhibited, after pre-incubation with GM1, anodal shifts characterized by variable degrees of polydispersity of migration, that likely reflected the formation of heterogeneous populations of micelles and/or aggregates of GM1 ganglioside and SARS-2-S conformers, as though the interaction with GM1 had a disordering effect upon these SARS-2-S variants. Investigation of the determinants of such diverse responses to the interaction with GM1 may help decipher how genetic variation can affect the fusogenic activity and infectivity of SARS-CoV-2 variants. Elucidating the contribution of GM1 binding to SARS-2-S-mediated viral attachment and entry into target cells might pave the way to the development of inhibitors of SARS-CoV-2 infection, based on multimers of oligosaccharides that mimic membrane-bound GM1.

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Chernyukh, O. G. "Qualitative detection of Ig G antibodies to SARS-CoV-2 coronavirus nucleocapsid antigen in the blood serum of patients who had viral respiratory infection, caused by SARS-CoV-2." Thesis, БДМУ, 2022. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19534.

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Gouin, Carla. "Tropisme cellulaire initial du SARS-CoV-2 dans le poumon humain : du poumon entier aux sous-populations de macrophages." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL147.

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Les mécanismes pathogéniques impliqués dans les phases initiales de l'infection par le SARS-CoV-2 restent mal compris au niveau pulmonaire, en dépit d'une abondante activité de recherche depuis l'émergence de la pandémie COVID-19. Des travaux conduits sur des modèles de culture de cellules humaines isolées, d'explants, d'organoïdes ou de lung-on-a-chip ont donné des résultats discordants quant aux cibles initiales pulmonaires principales du virus et à la réponse innée induite. Dans ce travail de thèse, j'ai évalué un modèle original d'étude des premières étapes de l'infection virale qui consiste à infecter un poumon humain entier maintenu vivant ex vivo selon une technique utilisée couramment en transplantation pulmonaire, permettant ainsi d'étudier l'infection dans des conditions respectant les interactions spatiales. Cette technique (perfusion pulmonaire ex vivo, PPEV) consiste à ventiler et perfuser des poumons pendant quelques heures et conduit à évaluer et réhabiliter des poumons dits marginaux. Par la technique de RNA-seq sur cellule unique, nous avons découvert que le poumon entier maintenu sous PPEV sans virus présente un programme d'activation génique particulier que nous avons exploré dans un premier volet de la thèse. Ainsi nous avons mis en évidence, que la PPEV en elle-même induit une réponse inflammatoire qui varie en fonction du temps et des types cellulaires. Cette réponse s'accompagne d'une signature génique indiquant une réduction de la signalisation du cytosquelette dans les cellules épithéliales alvéolaires de type 2 et les cellules endothéliales, ainsi qu'une réduction de la migration et de l'activation des lymphocytes et cellules dendritiques. Ce travail révèle pour la première fois la réponse biologique à la PPEV en fonction des types cellulaires, potentiellement associée à des effets sur les suites cliniques. Dans un second temps, nous avons infecté sous PPEV des poumons avec différents isolats viraux et réalisé des analyses de RNA-seq sur cellule unique qui ont révélé que les macrophages alvéolaires (AMs) et ceux dérivés des monocytes (MoMacs) sont les cibles principales du virus. Par contre, les cellules épithéliales et les sous-populations de monocytes pulmonaires ne sont pas significativement associées au virus. Nous avons étudié la réponse de différents types de monocytes/macrophages in vitro après dissociation de tissus pulmonaire humain, tri en cytométrie puis culture avec le virus. Nous avons révélé des réponses spécifiques inflammatoires en fonction des populations cellulaires, des souches virales et des doses, les cellules MoMacs étant les plus inflammatoires en réponse au virus. Ces résultats originaux mettent en évidence le rôle des macrophages à l'étape initiale de l'infection et suggèrent que leur réponse pourrait conditionner l'apparition des lésions ultérieures associées à la gravité en fonction de la composition initiale alvéolaire en sous populations de monocytes/macrophages, de la souche virale et de la dose. Dans un projet parallèle, j'ai étudié une méthode visant à réduire cette inflammation, sur poumon de porc, en procédant à une dialyse du perfusat pour éliminer les déchets métaboliques accumulés. Nous avons montré que la dialyse ne réduit pas l'inflammation, mais l'augmente plutôt, après 6 ou 12 heures.Au total, ce projet de thèse a montré les atouts et les limites d'un modèle d'infection virale de poumon entier maintenu ex vivo. Il a mis en lumière l'implication des sous-populations de monocytes/macrophages dans les premières étapes de l'infection par le SARS-CoV-2. Il a également conduit à mieux comprendre les mécanismes cellulaires et moléculaires impliqués dans la technique de maintien ex vivo du poumon, ce qui sera utile pour améliorer la conduite de la transplantation
The pathogenic mechanisms of the initial phase of the SARS-CoV-2 infection remain poorly understood at the pulmonary level, despite strong research efforts since the emergence of the COVID-19 pandemics. Studies conducted with various models, including isolated human cell cultures, explants, organoids or lung-on-a-chip systems have generated conflicting results concerning the primary pulmonary targets of the virus and the induced innate immune responses.In my thesis, I evaluated an original model for studying the early stages of viral infection. This model involves the infection of a whole lung that is maintained ex vivo with a technique used in lung transplantation, allowing the study of infection under conditions that preserve spatial interactions. This technique (ex-vivo lung perfusion, EVLP) involves ventilating and perfusing lungs for several hours and has the potential to evaluate and rehabilitate marginal lungs. We conducted single-cell RNA-seq analyses and we discovered that the whole lung maintained under EVLP without the virus displayed a specific gene activation program, which we analyzed in the first part of my thesis. We found that EVLP in itself induced an inflammatory response that varied over time and across cell types. This response was accompanied by gene signatures indicating reduced signaling of cytoskeleton in alveolar type 2 epithelial cells and endothelial cells, as well as reduced cell migration and activation of lymphocytes and dendritic cells. This work reveals, for the first time, the biological responses to EVLP based on cell types that may be related to the clinical outcomes. In the second part of my thesis, we infected lungs under EVLP with different viral isolates and conducted single-cell RNA-seq analyses. These analyses revealed that alveolar macrophages (AMs) and monocyte-derived macrophages (MoMacs) are the primary targets of the virus. Epithelial cells and pulmonary monocyte subpopulations were not significantly associated with the virus. We studied the response of the monocyte/macrophage populations in vitro after dissociation of human lung tissue, flow cytometry sorting and culture with the virus. We observed specific inflammatory responses depending on cell subsets, viral strain and doses, with MoMacs being the most inflammatory. Our original work reveals the role of monocyte/macrophage subsets in the initial phases of the SARS-CoV-2 infection and suggests that the initial response of alveolar monocyte/macrophages will drive the subsequent development of lung injuries, depending on the composition in AMs and MoMacs, the viral strain and doses. In a parallel project, we investigated the effects of a method aimed at reducing the inflammation during EVLP, on porcine lung, by performing a dialysis of the perfusate to remove accumulated metabolic wastes. However, our findings showed that dialysis did not reduce inflammation; rather, it increased inflammation after 6 or 12 hours.Overall, this thesis project has demonstrated the strengths and limitations of a whole lung viral infection model maintained ex-vivo. It has highlighted the involvement of monocyte/macrophage subpopulations in the initial step of SARS-CoV-2 infection and has also contributed to a better understanding of the cellular and molecular mechanisms involved in the ex vivo lung maintenance technique, which will be useful for improving lung transplantation procedures

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Venkatesan, Lavanya. "Identifying and Tracking the Evolution of Mutations in the SARS-CoV-2 Virus." Thesis, Virginia Tech, 2021. http://hdl.handle.net/10919/103939.

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SARS-CoV-2 is caused by a pathogenic and highly transmissible beta coronavirus leading to severe infections in immuno-compromised individuals. This study first evaluates the primers used in the Reverse Transcription Polymerase Chain Reaction (RT-PCR) to detect SARS-CoV-2 by understanding how mutations might affect the primer efficiency with the SARS-CoV-2 sequences. Mutations on the Spike protein of SARS-CoV-2 are the most important as the spike protein mediates the viral entry into host cells. This study tracks the course of mutations on the spike protein by focusing on the haplogroups of the sequences across the world. A comprehensive database linking three important, currently available databases is curated as part of this study to fill the gaps caused by sequencing errors. Further, this study exploits the data generated by the Illumina and Oxford Nanopore next generation sequencing methods to study the evolution of mutations in a single Septuagenarian patient over an infection period of 102 days using the gene analysis software Geneious Prime.
Master of Science
A novel corona virus named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has taken down the entire world by causing Covid-19 pandemic. Initially detected in Wuhan, China, the virus has now made its way to more than 200 countries with a heavy death toll. Understanding the virus through mutation tracking and improving diagnostics and vaccine design have now become the top priority of researchers. Most of these researchers depend on quality viral sequence datasets to identify and track mutations. One aim of this study is to provide a comprehensive dataset linking the GISAID (Global Initiative on Sharing All Influenza Data), NCBI (National Center for Biological Information) and the SRA (Sequence Read Archive) sequences. The dataset can be used for genome analysis and mutation tracking which can provide important insights for vaccine design and in improving diagnostic assays. In addition, this study provides an analysis of viral mutations in in the genomic regions targeted by commonly used primers in the RT-PCR tests for SARS-CoV-2 that may affect the efficiency of detection. This study also uses the haplogroup information of people across the world to track the D614G mutation on the S gene of SARS-CoV-2 as it may be associated with increased transmissibility. To track the course of mutations in SARS-CoV-2, it is important to analyze the sequencing data provided by the Illumina and Oxford Nanopore next generation sequencing methods. We present a case study to investigate the course of SARS-CoV-2 mutations in a single septuagenarian patient over a period of 102days using the Sequence Read Archive (SRA) data generated by two Next Generation Sequencing methods and compare the advantages that one has over the other.

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Svanberg, Linus, and Alexander Westberg. "Användning av e-hälsa under SARS-CoV-2 : En enkätstudie om distriktssköterskans upplevelse." Thesis, Högskolan i Borås, Akademin för vård, arbetsliv och välfärd, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-26072.

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Användandet av e-hälsa har ökat både nationellt och internationellt de senaste åren. Under SARS-CoV-2-pandemin har nyttjandet i Sverige varit explosionsartat, då icke-fysiska möten minimerar risken för smittspridning. Tidigare forskning visar att e-hälsa har positiva effekter, men ses också som ett hot av distriktssköterskor. Studien belyser därför distriktssköterskans upplevelse av arbetet med e-hälsa under den pågående pandemin och är en kvantitativ enkätstudie med induktiv ansats. Deltagarna rekryterades med hjälp av bekvämlighetsurval och begränsades till legitimerade sjuksköterskor och specialistsjuksköterskor inom primärvården. Den totala svarsfrekvensen var 48 %. Analysen av enkäterna genomfördes med hjälp av IBM SPSS Statistics. De analyser som utfördes var Spearmans rangkorrelation och Kruskal-Wallis icke-parametriska test. Resultatet visade att det fanns en brist i utbildning kring e-hälsa hos informanterna. E-hälsotjänsterna var inte användarvänliga och de var tidskrävande för informanterna. Tid avsattes inte heller för arbetet med e-hälsa på arbetsplatserna. Det fanns potential för minskad smittspridning av SARS-CoV-2 genom arbetet med e-hälsa förutsatt att den vård som gavs genom e-hälsa var av god kvalitet. Ytterligare studier bör genomföras för att få en djupare förståelse för vad som kan och bör förbättras med e-hälsotjänsterna.

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Marot, Stéphane. "Étude de la réponse humorale lors de l'infection par le SARS-CoV-2." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS722.

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Au début de la pandémie de COVID-19, nous ne disposions que de peu de données portant sur la réponse humorale spécifique anti-SARS-CoV-2 et elles étaient principalement issues des connaissances des coronavirus humains proches. L’objectif de ce travail était de décrire la cinétique de la réponse humorale et son activité neutralisante à la suite d’une infection par le SARS-CoV-2 ou au décours d’une vaccination contre le COVID-19. Dans notre première étude, nous avons pu décrire, chez des professionnels de santé ayant présenté un COVID-19 modéré, la cinétique d’apparition de différents isotypes d’anticorps dirigés contre différents antigènes viraux. Nous avons montré une disparition précoce de l’activité neutralisante sérique après l’infection, principalement liée à la disparition des IgA sériques et malgré une augmentation de la capacité de neutralisation des IgG au cours du temps. Dans notre seconde étude, nous avons décrit un échappement des variants du SARS-CoV-2 à cette réponse neutralisante, avec des profils d’échappement variables en fonction du variant et du type d’anticorps générés (post-infectieux ou post-vaccinaux). Dans notre dernière étude, nous avons évalué des tests de substitutions pour la détermination des anticorps neutralisants (NAbs) en fonction de différents variants du SARS-CoV-2 et de différents profils d’histoire immunologique. Nous avons montré une bonne performance de ces tests en adaptant les seuils en fonction du variant du SARS-CoV-2 considéré, un échappement important du variant Omicron aux NAbs et que le titre de NAbs était le plus élevé chez les personnes avec un antécédent de COVID-19 ayant reçu une dose de vaccin. Plusieurs études ont confirmé que les NAbs étaient fortement prédictifs de la protection immunitaire contre l'infection par le SARS-CoV-2. Toutefois, le déclin rapide de ces anticorps dans l’histoire naturelle de l’infection ou de la vaccination contre le SARS-CoV-2, associé à la circulation de variants échappant à la réponse neutralisante ainsi qu’à la variabilité individuelle de la réponse immunitaire et les différents profils d’histoire immunologique que l’on peut présenter, démontrent l’importance de l’étude des NAbs afin de pouvoir réévaluer en permanence les corrélats de protection en contexte d’évolution de la situation épidémiologique
At the beginning of the COVID-19 pandemic, we had limited data on the specific humoral response against SARS-CoV-2, only derived from knowledge of closely related human coronaviruses. The aim of this work was to describe the kinetics of the humoral response and its neutralizing activity following SARS-CoV-2 infection or COVID-19 vaccination. In our first study, we described the kinetics of different isotypes of antibodies directed against different viral antigens in healthcare workers who had experienced mild COVID-19. We observed an early decline in serum neutralizing antibodies (NAbs) after infection, primarily associated with the decrease in serum IgA levels, despite an increase in the neutralization capacity of IgG over time. In our second study, we described the escape of SARS-CoV-2 variants from NAbs, with escape profiles depending on the variant and the type of antibodies elicited (post-infection or post-vaccination). In our latest study, we evaluated surrogate tests for the assessment of NAbs, against different variants of SARS-CoV-2 and various immunological history patterns. We showed a good test performance by adjusting the thresholds based on the specific SARS-CoV-2 variant considered. We also found a significant escape of the Omicron variant from NAbs and showed that NAb titers were highest in individuals with a history of COVID-19 who had received a vaccine dose. Several studies have confirmed that NAbs are good correlates of immune protection against SARS-CoV-2 infection. However, the rapid decline of these antibodies in the natural course of infection or vaccination, coupled with the circulation of variants, as well as individual variability in the immune response, highlight the importance of studying NAbs to continuously reassess correlates of protection in the context of evolving epidemiological situations

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Lanata, de las Casas Claudio F., Ledesma Lucie Ecker, and Merino Ana I. Gil. "Avances en el desarrollo y el uso de las vacunas contra el SARS-CoV-2." Colegio Medico del Peru, 2021. http://hdl.handle.net/10757/656233.

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D'AGOSTINO, MATTIA. "Structural and biochemical characterization of the aIF5A-DHS complex / SARS-CoV-2 graphene biosensor based on engineered dimeric ACE2 receptor." Doctoral thesis, Università Politecnica delle Marche, 2022. https://hdl.handle.net/11566/299771.

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l mio progetto di dottorato si è concentrato sulla caratterizzazione strutturale e biochimica di un fattore di traduzione chiamato eIF5A e di uno dei suoi partner proteici, l'enzima deoxyhypusine synthase (DHS). Questo enzima è coinvolto nella modifica posttraduzionale di eIF5A, unica nella cellula ed è chiamata ipusinazione. eIF5A è overespressa in molte tipologie di cancoi ed è coinvolto in varie malattie, quindi lo sviluppo di inibitori che mirano al processo di ipusinazione è considerato una strategia terapeutica promettente. GC7, un inibitore che ha come target il DHS, è la molecola inibitrice dell'ipusinazione meglio caratterizzata, comunque il suo uso terapeutico è limitato per via della sua scarsa selettività. Nella prima parte del mio progetto di dottorato, ho eseguito uno studio comparativo tra il DHS umano e il DHS archea per comprendere le caratteristiche strutturali e dinamiche dell'inibizione data dal GC7, ciò mi ci ha permesso di trovare nuove dettagliate caratteristiche molecolari sul meccanismo di legame di questa molecola. Inoltre, abbiamo risolto per la prima volta la struttura tridimensionale del complesso aIF5A-DHS tramite diffrazione a raggi X. Questo importante traguardo apre la strada alla progettazione di nuovi e più specifici inibitori dell'ipusinazione. Durante il dottorato di ricerca, ho anche partecipato allo sviluppo di un biosensore basato sul grafene in grado di rilevare tutte le varianti conosciute di SARS-CoV-2.
My PhD project has focused on the structural and biochemical characterization of a translation factor called eIF5A and one of its interacting partners, the enzyme deoxyhypusine synthase (DHS). This enzyme is involved in eIF5A post-translational modification that is unique in the cell and it is called hypusination. eIF5A is overexpressed in several cancers and it is involved in various diseases, therefore, the development of inhibitors targeting hypusination process is considered a promising and challenging therapeutic strategy. GC7, an inhibitor targeting DHS, is the best-characterized hypusination suppressor, however its therapeutic use is limited by poor selectivity. In the first part of my PhD project, I have performed a comparative study between human DHS and archaeal DHS to understand the structural and dynamical features of the GC7 inhibition finding new detailed molecular insights into the binding mechanism of this molecule. Moreover, we have solved for the first time the three-dimensional structure of aIF5A-DHS complex via x-ray diffraction. This important goal opens the way to the design of new and more specific hypusination inhibitors. During the PhD, I have also participated in the development of a graphene-based biosensor able to detect all known SARS-CoV-2 variants.

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FALONE, MATTEO. "Trasporto di fluidi organici e di fluttuazioni di pressione: un approccio numerico alla termofluidodinamica." Doctoral thesis, Università Politecnica delle Marche, 2022. https://hdl.handle.net/11566/296981.

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I temi affrontati nella ricerca in ambito termofluidodinamico richiedono spesso un approccio multidisciplinare e tecniche di indagine non tradizionali. Una delle strategie più utilizzate, vista anche la sempre crescente disponibilità di risorse computazionali, è quella di operare con modelli numerici per la simulazione di fenomeni complessi, multifisici e multiscala. Una tematica di forte interesse ingegneristico è lo studio delle fluttuazioni di pressione derivanti dall’interazione tra un corpo e una corrente d’aria che lo investe: tale disturbo può ricadere nel campo dell’udibile e la sua diffusione può contribuire all’aumento dell’inquinamento acustico. Ne è un esempio il rumore prodotto dalle turbine eoliche di grande taglia per le quali sono state già state adottate tecniche di abbattimento del rumore, come l’impiego di bordi di uscita dentellati (trailing edge serration). Un altro tema di estrema rilevanza è quello del trasporto di fluidi organici veicolanti virus o batteri: la recente pandemia da SARS–CoV–2 ha messo in evidenza quanto sia importante valutare accuratamente la dinamica delle micro–gocce di saliva e la loro interazione termofluidodinamica con l’ambiente al fine di fornire corrette linee guida sulla distanza sociale e sulle buone pratiche da seguire nella quotidianità all’interno del contesto pandemico. In questo lavoro di tesi viene utilizzato un approccio numerico per lo studio dell’emissione aeroacustica prodotta da oggetti investiti da un flusso d’aria e della diffusione aerea di micro–particelle di fluido organico veicolanti virus. Viene sviluppato un solutore in grado di condurre simulazioni dirette (Direct Numerical Simulation – DNS) del campo aeroacustico, utilizzando condizioni al contorno non riflettive e schemi di integrazione temporale Runge–Kutta espliciti di alto ordine, e indagata la possibilità di adottare il riscaldamento localizzato quale tecnica di smorzamento delle fluttuazioni di pressione caratteristiche di un’onda sonora. Viene, inoltre, presentato un modello con approccio Euleriano–Lagrangiano multiscala, che permetta di valutare la diffusione in ambiente di particelle di fluido muco–salivare, nonché il processo di cristallizzazione della quota–parte salina delle droplet accoppiando il metodo Particle–Source–In–cell (PSI–cell) alla Population Balance Equation (PBE). Viene indagata anche la possibilità di ridurre la trasmissione di SARS–CoV–2 utilizzando la radiazione ultravioletta di tipo C quale tecnica di disinfezione real–time. I modelli sono sviluppati adottando il metodo di discretizzazione ai volumi finiti non strutturati e co–locati disponibile all’interno della libreria OpenFOAM.
The new issues addressed in scientific research in the thermal and fluid dynamic field often require a multidisciplinary approach and non–traditional investigation techniques. One of the most used strategies, also because of increasing availability of computational resources, is to operate with numerical models that allow the simulation of complex, multiphysics and multiscale phenomena. A cutting-edge topic is certainly the study of fluctuating pressure resulting from a body and air interaction: this disturbance can be such that to be in the hearing range and its diffusion can contribute to the increase in noise pollution and have a significant impact on our daily life. As an example, we can refer to the noise produced by multi–megawatt wind turbines that are often equipped with trailing edge serration in order to reduce the aeroacouistic emission. Another crucial topic in this moment is related to the organic fluids, carrying viruses or bacteria, diffusion: SARS–CoV–2 pandemic has highlighted how important is to understand and rigorous study saliva droplets dynamics and their interaction with the environment in order to provide guidelines on social distance and good practices to be followed in daily life. In this PhD thesis a numerical approach is used to study the aeroacoustic emission radiated by objects in a flow as well as to investigate airborne diffusion of organic fluid micro - particles carrying viruses. A new solver is developed in order to perform Direct Numerical Simulation of the aeroacoustic fields. Explicit high–order Runge–Kutta schemes are employed for time integration and non–reflective boundary conditions are adopted. The local wall heating effect fluctuating pressure is also investigated, in order to give an insight on a new method for active controlling the noise emission. Furthermore, a new computational model, developed in a multiscale Eulerian - Lagrangian framework, is presented. This approach allows to evaluate the spreading of micro–droplets emitted in respiratory activities, as well as their thermal and fluid dynamic interaction with the surrounding environment, taking also into account the droplet dry nuclei formation. Saliva sodium chloride crystallization kinetics is modelled by coupling Particle–Source–In–cell (PSI–cell) method with Population Balance Equation (PBE). Moreover, a real–time disinfection strategy is studied: biological inactivation of SARS–CoV–2 using ultraviolet–C radiation is addressed. The aforementioned models are developed adopting the unstructured, co–located, finite volume method available in the well-known OpenFOAM library.

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Schwarzer, Kira. "SARS-CoV-2 Pandemic from a Criminological Perspective - Investigating Antisocial Behaviour Changes in Germany." Thesis, Malmö universitet, Fakulteten för hälsa och samhälle (HS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-26428.

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The SARS-CoV-2 pandemic is not only a health crisis, but also shatters the socialand economic lives through regulations and social restrictions. As seen duringSARS 2002-2003, measures like social restrictions can impact behaviournegatively, leading to discrimination, stigmatisation and xenophobia. There is alack of studies on antisocial behaviour and crime during health crises, such aspandemics. Related studies on disaster and crime gave mixed results, with somesuggesting an increase in prosocial rather than antisocial behaviour. Using acriminological perspective, German news media from January 1, 2020 untilMarch 31, 2020 were analysed. These media sources were the tabloid Bild andtwo main elite newspapers, Süddeutsche Zeitung and Frankfurter AllgemeineZeitung. Analyses were conducted quantitatively based on frequencies, means andword counts. Additionally, a qualitative media content analysis regarding events,behaviour and story tone was undertaken. The aim was to reveal indications ofreported behavioural changes. For a complete overview, both antisocial andprosocial behaviours were included. Results indicate that antisocial behaviour,such as ignoring of governmental advice and rules, and discriminatory behaviours,as well as crimes like fraud became more prominent over time than prosocial andhelping behaviour. This study shows only a fragment of the situation in Germany,but highlights the importance of continuous assessments of human behaviourduring dynamic and critical times.

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Herrera, Añazco Percy. "SARS-CoV-2 y su efecto a nivel de tejido renal: Una revisión narrativa." Colegio Medico del Peru, 2021. http://hdl.handle.net/10757/656234.

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Se describe la evidencia actual del efecto del SARS-CoV-2 a nivel de tejido renal. Se realizó una revisión narrativa de los artículos publicados en SCOPUS y PUBMED hasta septiembre de 2020. Los resultados se dividieron en las siguientes secciones: evidencia del efecto directo del virus en el riñón, mecanismos de invasión celular, mecanismos de injuria celular y las potenciales implicaciones terapéuticas de estos hallazgos. El SARS-CoV-2 invade las células del túbulo proximal y los podocitos, a través del receptor ECA-2. La invasión y replicación viral podrían producir daño mediante un efecto citopático directo aunado a un daño mediado por la respuesta inmune. Debido a la expresión celular de ECA-2, se ha propuesto a los Inhibidores del Sistema Renina–Angiotensina–Aldosterona como un potencial tratamiento contra la COVID-19. Sin embargo, a la fecha, la evidencia no apoya su uso

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NGUYEN, HOANG OANH. "ANTI-INFLAMMATORY PROPERTIES OF PDE4 INHIBITION IN SARS-COV-2-ACTIVATED HUMAN DENDRITIC CELLS." Doctoral thesis, Università degli studi di Brescia, 2022. http://hdl.handle.net/11379/555422.

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È stato dimostrato che la risposta immunitaria disfunzionale e l’iper-infiammazione con conseguente tempesta citochinica giocano un ruolo chiave nello sviluppo di forme severe di malattia da Coronavirus 2019 (COVID-19). Tale condizione clinica suggerisce che l’eccessiva risposta immunitaria innata potrebbe scatenare una patologia immunitaria virus-dipendente. In questo lavoro, viene descritto un nuovo meccanismo di attivazione delle cellule dendritiche da parte del virus SARS-CoV-2. Nello specifico, sequenze di RNA del genoma virale sono in grado di attivare dei recettori endosomiali, in particolare il TLR7 e TLR8. L’attivazione di questi recettori da parte delle sequenze di RNA virale ha indotto in-vivo una forte infiammazione polmonare, come dimostrato dall’accumulo di mediatori pro-infiammatori e dall’infiltrato leucocitario, mentre in-vitro ha indotto una polarizzazione in senso Th1 ed un forte rilascio di interferoni e citochine pro-infiammatorie. Tanimilast è un nuovo inibitore selettivo della fosfodiesterasi 4, che viene assunto per via inalatoria, ed è impiegato in avanzati studi clinici per il trattamento della broncopneumopatia cronica ostruttiva e che potrebbe potenzialmente rivelarsi utile nel trattamento della polmonite da COVID-19. In questo progetto abbiamo visto come la potente attivazione delle cellule dendritiche da parte di sequenze di RNA del SARS-CoV-2 è stata notevolmente inibita dal trattamento con Tanimilast. Il trattamento con Tanimilast ha infatti causato una diminuzione del rilascio di citochine pro-infiammatorie (TNF-α e IL6) e chemochine (CCL3, CXCL9 e CXCL10), nonché alla riduzione del rilascio di citochine associate alla polarizzazione in senso Th1 (IL-12 ed Interferoni di tipo I). Tuttavia, il trattamento con Tanimilast non ha influito sull’espressione dei marker di maturazione quali CD83, CD86, MHC-II e CCR7. Coerentemente con ciò, il trattamento con Tanimilast non ha compromesso la capacità delle cellule dendritiche attivate di attivare i linfociti T CD4+, ma ha deviato la loro polarizzazione preferenzialmente verso un fenotipo Th2. Inoltre, Tanimilast ha inibito l’espressione di molecole MHC di classe I, limitando di conseguenza l’attivazione e il differenziamento dei linfociti T citotossici CD8+. Gli effetti immunomodulatori di Tanimilast sono stati ulteriormente confermati dalla sua capacità di promuovere il rilascio di molecole immunosoppressorie cAMP-dipendenti come IDO1, TSP1, VEGF-A e anfiregulina in cellule dendritiche stimolate con LPS. Queste cellule hanno anche fortemente over-espresso il CD141 e mostrato un incremento nella fagocitosi di cellule morte. Complessivamente, i nostri risultati indicano che Tanimilast promuove l’acquisizione di proprietà immunomodulatorie da parte delle cellule dendritiche mature, nonché un differente fenotipo semi-maturo associato ad una elevata sovra espressione del CD141. I dati permettono quindi di suggerire Tanimilast come un promettente farmaco immunomodulatorio per il trattamento di malattie immuno-mediate o infiammatorie, possibilmente includendo le polmoniti severe da COVID-19.
Dysfunctional immune response and hyper-inflammation with subsequent cytokine storm were shown to play a key role in the development of severe and fatal forms of Coronavirus disease 2019 (COVID-19). This clinical condition suggests that an overactive innate immune response may unleash virus-dependent immune pathology. Here, we described a novel mechanism of SARS-CoV-2-dependent activation of dendritic cells (DCs), based on the recognition of sequences of viral genomic ssRNA (SCV2-RNA) by endosomal pattern recognition receptors, namely TLR7 and TLR8. Importantly, SCV2-RNA recapitulated potent lung inflammation in vivo as shown by accumulation of proinflammatory mediators and immune cell infiltration; and induced a strong release of pro-inflammatory cytokines and Th1 polarization in vitro. Tanimilast is a novel and selective inhaled inhibitor of phosphodiesterases 4 that is in advanced clinical development for the treatment of chronic obstructive pulmonary disease and could prove beneficial in severe COVID-19 pneumonia. In our experimental setting, the potent activation of DCs by SCV2-RNA was severely blunted by Tanimilast, which decreased the release of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (CCL3, CXCL9, and CXCL10) and of Th1-polarizing cytokines (IL-12, type I IFNs). However, Tanimilast did not impair the acquisition of the maturation markers CD83, CD86, HLA-DR and CCR7. Consistent with this, Tanimilast did not reduce the capability of activated DCs to activate CD4+ T cells but skewed their polarization towards a Th2 phenotype. In addition, Tanimilast blocked the increase of HLA class I molecules and restrained the proliferation and activation of cytotoxic CD8+ T cells accordingly. The immune-modulatory effects of Tanimilast were further demonstrated by its capacity to enhance cAMP-dependent immunosuppressive molecules such as IDO1, TSP1, VEGFA and Amphiregulin in LPS-stimulated DCs. These cells also strongly upregulated CD141 and displayed increased uptake of dead cells. Altogether, our results indicate that Tanimilast induce mature DCs to acquire immunomodulatory properties as well as a distinct semi-mature phenotype, associated with the prominent expression of CD141, thus proposing Tanimilast as a promising immunomodulatory drug for the treatment in inflammatory or immune-mediated diseases, possibly including severe COVID-19 pneumonia.

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Gambino, Adèle. "Etude du rôle de l'immunité innée dans la physiopathologie et dans la transgression de la barrière d'espèces par le SARS-CoV-2 chez différentes espèces animales." Electronic Thesis or Diss., Maisons-Alfort, École nationale vétérinaire d'Alfort, 2024. http://www.theses.fr/2024ENVA0004.

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Le SARS-CoV-2 est un virus de la famille des Coronaviridae, genre Betacoronavirus qui aurait pour origine un virus proche provenant d'une espèce de chauve-souris. Son émergence en Chine fin 2019 ainsi que l'apparition de nombreux variants ont donné lieu à la plus grande pandémie virale du XXIème siècle. L'infection va engendrer la maladie COVID-19 qui est caractérisée par des symptômes respiratoires pouvant être de légers à sévères avec une pneumonie parfois fatale. La réponse immunitaire innée est la première ligne de défense contre une infection virale et permet la synthèse d'interférons (IFN) qui vont induire la production de centaines de molécules antivirales (Interferon-stimulated genes, ISG). Elle peut aussi contribuer à l'établissement d'une inflammation possiblement délétère. Nous avons souhaité étudier l'implication de la réponse IFN dans la physiopathologie du SARS-CoV-2 par deux approches : chez des hamsters syriens infectés par des variants (D614G, Delta, Omicron) du SARS-CoV-2 de pathogénicité différente et dans un modèle de souris déficientes ou non pour le récepteur de l'interféron de type I. Nous montrons dans le modèle du hamster Syrien, une corrélation positive au premier jour post-infection de la cavité nasale entre l'intensité de la réplication virale, la réponse IFN de type III et la synthèse de cytokines inflammatoires. Le variant Delta cause des dommages tissulaires plus précocement dans l'épithélium olfactif associés à des réponses IFN et inflammatoires très fortes. Le variant Omicron, le moins pathogène, est celui qui induit plus lentement une réponse interféron avec une réponse inflammatoire amoindrie. Cependant, dans le modèle murin, nous montrons que la réponse IFN-I est nécessaire pour contrôler la réplication virale. Si à des temps très précoces de l'infection, le défaut d'induction de la voie IFN-I ne semble pas délétère, au 4ème jour post-infection, en lien avec la réplication et diffusion accrue du virus, le niveau des cytokines inflammatoires est au final similaire à celui des souris contrôles et nous observons dans la cavité nasale une augmentation des lésions tissulaires. La réponse IFN peut aussi être un facteur déterminant dans la capacité d'un virus à franchir la barrière d'espèce. En effet, l'aptitude d'un virus à contrecarrer la réponse IFN de différents hôtes potentiels pourrait favoriser le franchissement de la barrière d'espèce. Certaines protéines du SARS-CoV-2 sont capables d'inhiber la voie d'induction des ISGs dans les cellules humaines et nous nous sommes demandés si les orthologues viraux des virus SARS-CoV-like de chauve-souris conservent cette propriété. Nous montrons ainsi que comme pour le SARS-CoV-2, la protéine virale Nsp13 des virus BANAL-236, BANAL-103 et RATG13 qui infectent les chauves-souris, inhibent aussi l'induction de la voie IFN humaine. Ainsi, l'induction de la voie interféron a de conséquences multiples au cours de l'infection virale et les virus, comme le SARS-CoV-2 peuvent de diverses manières contrecarrer son induction ce qui confère un avantage réplicatif. Son étude reste importante pour mieux comprendre la physiopathologie de la maladie et adapter au mieux les traitements antiviraux mais aussi pour détecter des virus animaux qui pourraient détourner facilement les réponses antivirales des cellules humaines et avoir ainsi un potentiel zoonotique
SARS-CoV-2 is a virus from the Coronaviridae family, Betacoronavirus genus, which is believed to have originated from a closely related virus found in a species of bat. Its emergence in China at the end of 2019 and the appearance of numerous variants have led to the largest viral pandemic of the 21st century. The infection causes the disease COVID-19, characterized by respiratory symptoms ranging from mild to severe, with pneumonia that can sometimes be fatal. The innate immune response is the first line of defense against a viral infection and allows for the synthesis of interferons (IFN), which induce the production of hundreds of antiviral molecules (Interferon-stimulated genes, ISG). It can also contribute to potentially harmful inflammation. We aimed to study the involvement of the IFN response in the pathophysiology of SARS-CoV-2 through two approaches: in Syrian hamsters infected with SARS-CoV-2 variants (D614G, Delta, Omicron) of different pathogenicity and in a mouse model deficient or not for the IFN-I receptor. We show in the Syrian hamster model a positive correlation on the first day post-infection of the nasal cavity between the intensity of viral replication, the IFN-III response, and the synthesis of inflammatory cytokines. The Delta variant causes tissue damage earlier in the olfactory epithelium, associated with very strong IFN and inflammatory responses. The Omicron variant, the least pathogenic, induces an interferon response more slowly with a reduced inflammatory response. However, in the mouse model, we show that the IFN-I response is necessary to control viral replication. If at very early times of infection, the lack of induction of the IFN-I pathway does not seem harmful, on the 4th day post-infection, linked to increased viral replication and dissemination, the level of inflammatory cytokines is ultimately similar to that of control mice, and we observe an increase in tissue lesions in the nasal cavity. The IFN response can also be a determining factor in a virus's ability to cross the species barrier. Indeed, a virus's ability to counteract the IFN response of different potential hosts could facilitate crossing the species barrier. Some SARS-CoV-2 proteins can inhibit the induction of ISGs in human cells, and we wondered if the viral orthologs of bat SARS-CoV-like viruses retain this property. We show that, like SARS-CoV-2, the viral protein Nsp13 of the viruses BANAL-236, BANAL-103, and RATG13, which infect bats, also inhibit the induction of the human IFN pathway. Thus, the induction of the interferon pathway has multiple consequences during viral infection, and viruses like SARS-CoV-2 can counteract its induction in various ways, which confers a replicative advantage. Its study remains important to better understand the pathophysiology of the disease and to better adapt antiviral treatments, but also to detect animal viruses that could easily circumvent the antiviral responses of human cells and thus have zoonotic potential

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Fui, Annalisa. "COVID-19 pneumonia in a wide Italian cohort of sarcoidosis patients." Doctoral thesis, Università di Siena, 2021. http://hdl.handle.net/11365/1133308.

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Introduction: At the beginning of coronavirus diseases 2019 (COVID-19) outbreak, there was concern that infected sarcoidosis patients, likewise other patients with chronic lung disease, could be at higher risk of a poor outcome and death. Moreover it was supposed that Sarcoidosis infected patients could be at higher risk of poor outcome ùs as a consequence of comorbidities secondary to chronic glucocorticoid treatment. Methods:In order to determine whether sarcoidosis patients really showed high risk of poor outcome and death during COVID-19 pandemic, an electronic survey of the impact of COVID-19 on sarcoidosis patients was proposed together with the University of Cincinnati to the Italian Sarcoidosis association Amici contro la Sarcoidosi (ACSI). Results: The clinical features of 1542 sarcoidosis patients, were anonymously collected by telephone survey and online questionnaire from April to June 2020). In this group,32 patients (2.1%) declared that they had contracted SARS-CoV-19 infection. 6 patients of them (19%) were hospitalized (among these, 2 patients were admitted to intensive care unit). 4 out of 32 patients (12%) were health care workers, while 15 (47%) reported having comorbidities and 14 out of 32 (44%) have a form of pulmonary sarcoidosis only, 12 (37%) have both pulmonary and extrathoracic involvement. Contrary to initial concerns about prognosis, our results suggest that patients with sarcoidosis did not have an increased risk of adverse outcome or death from COVID-19 infection compared to the general population. Almost half of our patients with sarcoidosis and SARS-CoV-2 had at least one of the following diseases: hypertension, asthma, COPD, diabetes and obesity. The subgroup of sarcoidosis patients developing COVID infection in our sarcoidosis cohort was characterized by lung involvement, high prevalence of comorbidities and treatment suggesting that these clinical parameters may be potential risk factors of developing COVID-19.

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Casa, Elisa. "Cell based assays used to quantify neutralizing antibodies against SARS-CoV-2 in human samples." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1189903.

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Since the SARS-CoV-2 outbreak at the end of December 2019 in China, it has become extremely important to have well‐established and validated diagnostic and research-use-only assays for this new emerging virus. The microneutralization assay is a fundamentalserological test in virology, immunology, vaccine assessment and epidemiological studies, and represents one of the most used methods to evaluate the immune response induced by SARS-CoV-2 infection or vaccination. In this Phd project different microneutralization methods are presented which can be used to measure anti‐SARS‐CoV‐2 neutralizing antibodies (nAbs) in human serum samples. The aim of the first project of this thesis (Project I) was to compare a microneutralization assay (MN) with a read out based on the cytophatic effect (CPE) and a MN based on a colorimetric read out for the detection of nAbs against SARS-CoV-2 Wild type strain. In the first method the cell monolayers were microscopically inspected for inhibition of CPE at each serum dilution (subjective method), while in the MN based on a colorimetric read out the healthy cell monolayer was stained with neutral red solution, a vital dye. The plates were then read by a spectrophotometer at 540 nm (objective method). A panel of 83 human serum samples were previously tested in enzyme‐linked immunosorbent assay (ELISA) as a pre‐screening. All the samples found to be positive, borderline, and negative in this ELISA were then tested to determine the nAbs titers through the MN CPE and Colorimetric MN. The comparison between log2-trasformed MN titers obtained through these two methods showed comparable values, and the strong agreement in evaluating neutralizing antibodies against SARS-CoV-2 Wild type strain was also confirmed by Correlation (r 2=0,9955), Bland-Altman, and intra-class correlation (ICC) analysis (ICC value of 0.993, which is indicative of an excellent agreement). This suggests the suitability of performing the MN assay using an ‘objective’ colorimetric-based read out method. To better investigate if the classical MN CPE yielded similar results to those obtained with other MN methods, we compared this “classical” MN to a new MN platform: the Virospot MN assay (Project II). This method combines classic virus culture techniques with automated sensitive detection of immunostained virus infected cells. In the Virospot MN, a virus-specific immunostaining was used for plate reading and then the images of all wells were acquired by a CTL ImmunoSpot analyzer. The 80% (MN80) or 90% (MN90) neutralization titers are calculated according to the method described by Zielinska et al. 2005. This titer calculation is based on the serum dilutions above and below the reduction point, 80% or 90% neutralization. The MN CPE and Virospot methods were compared using a panel of 47 human serum samples against SARS-CoV-2 Wild type and Alpha variant. The results of this project showed that the these two different MN assays produce similar titer results against the Wild Type virus, with good correlation values (correlation MN80 r2=0,9091; correlation MN90 r2=0,8900). A lower agreement between the MN CPE and Virospot MN assay was observed when SARS-CoV-2 Alpha variant was used (correlation MN80 r2=0,7226; correlation MN90 r2=0,6673). Overall, these results showed a good agreement between the MN CPE assay and the two different MN methods, Colorimetric MN and Virospot MN assay, in detecting neutralizing antibodies against SARS-CoV-2 in human serum samples. Despite the need for further standardization and/or the differences noticed during the assessment of nAbs against SARS-COV-2 variants, the Colorimetric-based and Virospot MN demonstrate to have advantages over the classical MN CPE, both being completely automated methods, and hence offering a higher throughput, while inspection of each dilution well by means of the optical microscope slows down the process. However, to ensure that these correlation studies can provide meaningful results, further analysis with a bigger number of samples and with other SARS-CoV-2 variants would be an added value. Moreover, to make the data more comparable it would be necessary convert all the results to international standard unit (IU/mL) allowing the accurate calibration of assays to an arbitrary unit, thereby reducing inter-laboratory variation, and creating a common language for reporting data. The SARS-CoV-2 Virospot MN assay offers attractive advantages over the MN assay with a read out based on the cytophatic effect, including the relative insensitivity to variation in amount of infectious virus used in the test, independence from virus replication kinetics and suitability for high throughput analyses. Since many new SARS-CoV-2 variants occurred during the last two years, to make the Virospot more sensitive and robust in detecting neutralizing antibodies against these new variants, the third project (Project III) focused on the optimization study of this MN assay. Several new conditions were adapted to optimize the method and make it more sensitive for the analysis of samples against the Wild Type, Alpha, Beta, and Gamma SARS-CoV-2 variants. Carboxymethyl cellulose (CMC) overlay was introduced to make the spot count more accurate avoiding the viral spread after the first infection. Moreover, different sample matrices (serum and plasma), culture media with and without the CO2 supplementation, and different incubation time points and temperatures were assessed to evaluate and improve the assay performance and robustness. This optimization study has a planned follow-up, which can possibly include samples not only from infected/convalescent individuals but also from vaccinated donors (with two or more doses) or from people with hybrid immunity (such as breakthrough infections). Additionally, further analyses with additional SARS-CoV-2 variants to strengthen these finding will also be part of the next study. This project is worth to be conducted as the Virospot MN assay is likely to have importance for the pre-clinical evaluation and eventual licensing of the SARS-CoV-2 vaccines.

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Celotto, Mattia <1995&gt. "Il MES, il Recovery Fund e i vantaggi dell'Eurozona ai tempi del SARS-CoV-2." Master's Degree Thesis, Università Ca' Foscari Venezia, 2021. http://hdl.handle.net/10579/19479.

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The thesis aims to look at the history of the European Union, from the end of the Second World War to the establishment of the ESM. Two focuses, one about the ESM itself, one about the Recovery Fund, constitute the pivotal part of the thesis. Finally, a look at the situation of Italy and its problems reguarding its lack in adapting to the Eurozone and the Euro are done to imply how problems that developed in the country since the Seventies can't be attribueted to the European single currency.

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Garnier, Nathalie. "De l'étude du rôle des miARN dans la physiopathologie de l'infection par le SARS-CoV-2 à l'élaboration d'une application clinique." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS035.

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Le coronavirus 2 du syndrome respiratoire aigu sévère (severe acute respiratory syndrome-related coronavirus, SARS-CoV-2), de la famille Coronaviridae, est responsable de la maladie à coronavirus de 2019 (coronavirus disease 2019, COVID-19). Malgré la disponibilité de vaccins, en cause dans la fin de l’urgence sanitaire de la COVID-19, la circulation virale du SARS-CoV-2 subsiste ainsi que les recherches sur la compréhension de sa physiopathologie, notamment l’implication et le rôle des microARN (miARN) dans cette infection virale. Les miARN sont des petits ARN non codants régulant l’expression des gènes et connus pour leurs implications dans de nombreuses voies de régulation cellulaire. Récemment, ils se sont révélés l’être également dans l’infection par le SARS-CoV-2. Ces recherches permettraient une meilleure connaissance dans ce domaine et pourraient s’avérer utiles dans le développement de nouveaux diagnostics et de traitements cliniques contre cette infection virale ou d’autres infections de la même famille virale. Ainsi, dans ce projet de recherche, nous avons d’abord caractérisé les miARN cellulaires biomarqueurs de l’infection virale par le SARS-CoV-2 à partir de prélèvements nasopharyngés de patients, qui est le prélèvement recommandé pour le diagnostic de cette infection virale. Nos travaux ont identifié en particulier, des miARN associés à des formes sévères de la COVID-19. Ces derniers ciblent des gènes impliqués dans les infections virales et les réponses antivirales et anti-inflammatoires aux infections virales. Ces potentiels effets antiviraux et anti-inflammatoires des miARN sur l’infection virale par le SARS-CoV-2 n’ont pas pu être démontrés in vitro lors de cette étude. Par la suite, on s’est penché sur l’hypothèse de la dérégulation de la biogénèse des miARN par cette infection virale. On a trouvé aucune sous-expression des ARNm des gènes impliqués de la voie de biogénèse des miARN lors de l’infection par le SARS-CoV-2, que ce soit en ex vivo ou en in vitro. Pour finir, nous avons voulu développer un possible traitement clinique contre l’infection virale par le SARS-CoV-2 ou tout autre pathologie par la délivrance de miARN d’intérêt. Il s’agirait de développer des nanoparticules et des nanomatériaux couplés à des miARN ou autres ARN doubles brins messagers ou non, afin de permettre l’entrée de ces derniers au sein des cellules et rétablir ainsi l’expression basale des gènes impliqués dans l’infection virale
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), a member of the Coronaviridae family, is responsible for coronavirus disease 2019 (COVID-19). Despite the availability of vaccines that helped end the COVID-19 health emergency, the viral circulation of SARS-CoV-2 remains, as well as research on the understanding of its pathophysiology, in particular the involvement and role of microRNAs (miRNAs) in this viral infection. miRNAs are small non-coding RNAs that regulate gene expression and are known to be involved in numerous cellular regulatory pathways. Recently, they have also been shown to be involved in SARS-CoV-2 infection. Such research would provide a better knowledge in this field and could be useful in the development of new diagnoses and clinical treatments against viral infection with SARS-CoV-2 or other infections of the same viral family. Thus, in this research project, we first characterized the cellular miRNA biomarkers of SARS-CoV-2 viral infection from patient nasopharyngeal swabs, which is the first diagnostic tool for this viral infection. In particular, our work has identified miRNAs associated with severe forms of COVID-19. These miRNA target genes involved in viral infections and antiviral and anti-inflammatory responses to viral infections. These potential antiviral and anti-inflammatory effects of miRNAs on SARS-CoV-2 viral infection could not be demonstrated in vitro in this study. Then, the hypothesis of deregulation of miRNA biogenesis by this viral infection was investigated. No under-expression of mRNAs of genes involved in the miRNA biogenesis pathway was found upon infection with SARS-CoV-2, either ex vivo or in vitro. Finally, based on a miRNA of clinical interest, we wanted to develop a possible clinical treatment against viral infection by SARS-CoV-2 or any other pathology through the delivery of miRNAs of interest, in this case antiviral. This would involve developing nanoparticles and nanomaterials coupled to miRNAs or other double-stranded messenger or non-messenger RNAs, to enable the latter to enter cells and thus restore basal expression of the genes involved in viral infection

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Carbonnel, Marie. "Enjeux immunologiques liés à la grossesse, à propos de deux modèles : la transplantation utérine et l’infection à SARS-CoV-2." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS521.pdf.

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La transplantation utérine est un nouveau traitement permettant aux femmes avec une infertilité utérine d’être enceintes. Cette greffe d’organe est tout à fait unique car son but est l’obtention d’un enfant en bonne santé et le greffon est transitoire. Néanmoins, elle nécessite un traitement immunosuppresseur comme les autres greffes d’organes. Le but de mon travail de thèse était de mieux comprendre les mécanismes en jeu dans le rejet de greffe utérine et l’impact des altérations immunologiques sur l’interface materno-foetale. Sur une série rétrospective de biopsies de col analysées par RNA seq et imagerie de spectrométrie de masse, j’ai pu identifier certains mécanismes dont 2 inédits : la présence de structures lymphoïdes tertiaires en lien avec le rejet chronique et humoral et des macrophages sécrétant du granzyme B en lien avec un rejet sévère et une altération définitive de l’utérus le rendant impropre à porter une grossesse à terme. J’ai initié une cohorte prospective (MARNI) afin de regarder de manière longitudinale et plus précise ces mécanismes. Sur l’analyse de la première patiente, j’ai conforté certains résultats retrospectifs et mis en évidence deux potentiels biomarqueurs de rejet sanguin (granzyme B et IL1β). J’ai constaté une immunomodulation particulière liée aux immunosuppresseurs et à la grossesse. Je retrouve dans mes travaux un lien entre altérations du microbiote, infection, modulation de l’immunité innée et rejet. Afin de mieux appréhender l’interface materno-fœtale, j’ai mené en parallèle une étude sur le SARS-CoV-2 et la grossesse (MATERCOV). J’ai constaté que dans la majorité des cas, le rôle de barrière était rempli par une modulation des cellules immunitaires innées NK et macrophages ainsi que le rôle protecteur des oestrogènes. Des anomalies des cellules NK ont été responsables de pathologies impliquant le placenta comme celui de la mort fœtale dans MATERCOV et celui de la préeclampsie dans la greffe utérine. J’ai montré une empreinte immunitaire du nouveau-né dans MATERCOV. Dans la greffe utérine, elle reste à évaluer, bien que nous puissions déjà mentionner une altération du microbiote. La poursuite de mes travaux sur une plus grande série, ainsi que le suivi des enfants à moyen et long terme seront nécessaires pour étayer mes hypothèses
Uterine transplantation is a new treatment enabling women with uterine infertility to become pregnant. This organ transplant is unique in that its aim is to have a healthy child, and the graft is transient. Nevertheless, it requires immunosuppressive treatment like other organ transplants. The aim of my phd was to gain a better understanding of the mechanisms involved in uterine graft rejection and the impact of immunological alterations on the maternal-fetal interface. Based on a retrospective series of cervical biopsies analyzed by RNA seq and imaging mass cytometry, I was able to identify some mechanisms, including 2 novel ones: the presence of tertiary lymphoid structures associated with chronic, humoral rejection, and granzyme B secreting macrophages associated with severe rejection and definitive alteration of the uterus, making it unfit to carry a pregnancy to term. I set up a prospective cohort (MARNI) to take a longitudinal and more precise look at these mechanisms. Based on the analysis of the first patient, I confirmed some retrospective results and highlighted two potential biomarkers of blood rejection (granzyme B and IL1β). I observed a particular immunomodulation linked to immunosuppressive therapy and pregnancy. My work showed a link between alterations in the microbiota, infection, modulation of innate immunity and rejection. In parallel, to better understand the materno-foetal interface I conducted a study on SARS-CoV-2 and pregnancy (MATERCOV). I found that in the majority of cases, the placenta barrier role was fulfilled by modulation of the innate immune cells NK and macrophages, as well as the protective role of estrogens. Abnormalities in NK cells were responsible for pathologies involving the placenta, such as fetal death in MATERCOV and preeclampsia in uterine transplantation. I have shown an immune imprinting of the newborn in MATERCOV. In uterine transplantation, this remains to be assessed, although we can already mention an alteration in the microbiota. Further work on a larger series, as well as medium- and long-term follow-up of the children, will be necessary to substantiate my hypotheses

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Galmiche, Simon. "Identifying the settings at risk of transmission of SARS-CoV-2, the role of children in household transmission, and the incubation period of the main variants in an online case-control study in France." Electronic Thesis or Diss., Sorbonne université, 2024. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2024SORUS144.pdf.

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Notre objectif était d’identifier, pour l’infection à SARS-CoV-2, les lieux de transmission, le rôle des enfants dans la transmission intra-domiciliaire et la période d’incubation. Dans une étude cas-témoins en France métropolitaine incluant des adultes avec infection récente et des témoins non infectés appariés sur l’âge, le sexe, la région, la taille de population, et la semaine, nous avons estimé les odds ratios d’infection par le SARS-CoV-2 pour certains lieux d’intérêt, comportements, activités et la présence d’enfants au domicile. Nous avons analysé les circonstances de transmission décrites par les cas. Nous avons étudié l’effet de l’isolement entre un enfant infecté et les parents au sein des foyers, et la période d’incubation pour différents variants. D’octobre 2020 à octobre 2022, nous avons inclus 691454 cas et 57065 témoins. Après appariement de 175688 cas avec 43922 témoins (4 :1) durant l’étude divisée en neuf périodes, nous avons identifié un risque augmenté d’infection associé aux bureaux partagés, transports en commun et lieux de loisirs. Parmi les cas ayant identifié la source de transmission, celles-ci avaient lieu principalement dans les foyers, auprès de la famille élargie ou d’amis, ou sur le lieu de travail. Les personnes vivant avec des enfants avaient un risque augmenté d’infection, mais l’isolement d’un enfant infecté (notamment l’aération des espaces clos) était associé à une diminution de la transmission. La période d’incubation du variant omicron était environ 1 jour plus courte que pour le variant historique. Cette étude apporte des éléments de preuve sur la transmission du SARS-CoV-2 qui contribueront à la préparation aux prochaines pandémies
We aimed to identify the community settings associated with the risk of SARS-CoV-2 infection, the role of children in household transmission, and the incubation period of the SARS-CoV-2 infection. In a case-control study conducted in mainland France among adults with recent infection and uninfected controls matched on age, sex, region, population size, and calendar week, we estimated the odds ratios of SARS-CoV-2 infection for community settings, behaviours, activities, and children presence in the household. We leveraged the case series to describe the circumstances of transmission. We studied the effect of intra-household isolation from a child with ongoing infection. We determined the incubation period across variants of SARS-CoV-2. Between October 2020 and October 2022, we included 691,454 cases and 57,065 controls. After matching 175,688 cases with 43,922 controls (4:1) across the study divided into nine periods, we identified the risk associated with shared offices, shared transport, and leisure activities. Among the cases who could identify the source of transmission, the most reported transmissions took place in the household, with extended family or friends, or in the workplace. People living with children were at increased risk of infection, but isolation from an infected child (particularly ventilation of indoor areas) was associated with decreased transmission. The incubation period of the omicron variant was shorter by approximately 1 day compared with the historical strain. The evidence provided by this study on the transmission of SARS-CoV-2 will help design mitigation strategies in the context of pandemic preparedness

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Alves, Ana Raquel Catarino. "SARS-CoV-2 : um problema mundial." Master's thesis, 2021. http://hdl.handle.net/10400.26/38836.

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Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
O SARS-CoV-2 é um Coronavírus pertencente ao género Betacoronavirus que surgiu em Wuhan, na China, em dezembro de 2019 e que se introduziu nos seres humanos através de uma transmissão zoonótica, propagando-se através de contactos próximos com indivíduos infetados ou objetos contaminados, rapidamente por todo o mundo, perpetuando milhões de mortes. O SARS-CoV-2 é um vírus caraterizado por possuir um RNA de cadeia simples com polaridade positiva, que permanece em constante evolução e que é composto principalmente por quatro proteínas estruturais (S, M, E e N) que estão envolvidas no processo de entrada do vírus nas células do hospedeiro e na consequente replicação viral, que acontece inicialmente através da ligação da proteína S ao ACE2 expresso em várias células de diferentes órgãos do hospedeiro, principalmente no trato respiratório. Este vírus é o agente etiológico da COVID-19, doença altamente infeciosa e capaz de provocar uma infeção respiratória que pode ser ligeira e assintomática ou culminar em morte, maioritariamente em idosos ou indivíduos com comorbilidades. O diagnóstico precoce de indivíduos infetados pelo SARS-CoV-2 através de NAAT ou TRAg é essencial no controlo da transmissão viral na comunidade e uma terapêutica específica, eficaz e segura é crucial para tratar os infetados. Contudo, é ainda necessária mais investigação nesta área que tem tido resultados não consensuais na comunidade científica, não existindo ainda nenhuma terapêutica específica aprovada e disponível. Prevenir esta infeção, passa por adotar tanto medidas de reeducação, como de vacinação da população. As vacinas atualmente disponíveis no mercado basearam-se em diferentes métodos, nomeadamente, mRNA, vetores virais, vírus inativados e subunidades de proteína.
SARS-CoV-2 is a Coronavirus belonging to the Betacoronavirus gender that emerged in Wuhan, China, in December 2019 and was introduced into humans through zoonotic transmission, spreading through close contacts with infected individuals or contaminated objects, rapidly throughout the world, perpetuating millions of deaths. SARS-CoV-2 is a virus characterized by having a single-stranded RNA with positive polarity, which remains in constant evolution and is mainly composed of four structural proteins (S, M, E and N) that are involved in the entry process of the virus in the host cells and in the consequent viral replication, which occurs through the binding of protein S to ACE2 expressed in several cells from different host organs, mainly in the respiratory tract. This virus is the main cause of COVID-19, a highly infectious disease, capable of causing a respiratory infection that can be mild and asymptomatic or lead to death, mainly in the elderly or with comorbilities. Early diagnosis of SARS-CoV-2 infected individuals through NAAT or TRAg is essential in controlling viral transmission in the community and specific, effective and safe therapy is crucial to treat those infected. However, there is still a need for more research in this area, which has non-consensual results in the scientific community, without an available and approved specific therapy yet. Preventing this infection involves adopting both reeducation measures and population vaccination. Vaccines currently available on the market were based on different methods such as mRNA, viral vectors, inactivated virus and protein subunits.

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Pereira, Nádia Neves. "SARS-COV-2 characterization – an in silico approach." Master's thesis, 2021. http://hdl.handle.net/10316/98035.

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Dissertação de Mestrado em Bioquímica apresentada à Faculdade de Ciências e Tecnologia
O SARS-CoV-2 (Síndrome Respiratório Agudo Grave Coronavírus-2) já infetou mais de 225 milhões de pessoas e foi responsável por mais de 4,64 milhões de mortes em quase dois anos, tornando-se a última pandemia mundial. Ainda há muito que saber sobre este vírus e, tendo em conta a enorme quantidade de dados que surgiram desde a sua descoberta, pensámos numa abordagem que nos permitisse obter diferentes camadas de informação. Usámos text mining para obter informações de 179.984 artigos e obtivémos 10.325 genes humanos. Em seguida, usando o clusterprofiler, foi possível realizar uma análise de enriquecimento com as databases GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) e MeSH (Medical Subject Headings). Os resultados de diferentes databases corresponderam, o que significa que vários termos enriquecidos estavam presentes nas diferentes análises. Analisando os resultados finais percebemos que a concentração do ião de cálcio tem um enorme impacto na evolução do COVID-19 (Coronavirus Disease 2019), a doença causada pela infeção por SARS-CoV-2. O stress oxidativo e a exposição a níveis baixos de oxigénio também são responsáveis pela evolução da severidade do COVID-19. Descobrimos múltiplos genes associados com vários dos termos enriquecidos, inclusive alguns genes que estão associados com os vários termos e a entrada e/or replicarão do SARS-CoV-2 em células humanas. Para resultados mais significativos seria necessário uma analise mais profunda e mais cuidada destes dados .
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) infected over 225 million people and was responsible for over 4.64 million deaths in almost two years, becoming the last worldwide pandemic. There is still a lot to know about this virus and, considering the huge amount of data that appeared since the virus was discovered, we needed un approach to obtain different layers of information. We used text mining techniques to gather information from 179.984 articles and we were able to retrieve 10.325 human genes. Then, we performed enrichment analysis with GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) and MeSH (Medical Subject Headings) databases. The results from the different databases matched, meaning that various enriched terms were present in the different analysis. Analysing the final results we realise that calcium ion concentration has a huge impact on the evolution of COVID-19 (Coronavirus Disease 2019), the disease caused by the SARS-CoV-2 infection. Oxidative stress and exposure to low oxygen levels are also responsible for the evolution of COVID-19 severity. We discovered multiple genes associated with several of the enriched terms, including some genes that are associated with the various terms and the entry and/or replication of SARS-CoV-2 in human cells. Further and more careful analysis of these data would be required for more meaningful results. This means that this research may be continued and taken to a deeper level, in order to find new results.

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Parreiras, Susana Catapirra Magessi. "Rationally Designed Antiviral Proteins Targeting SARS-CoV-2." Master's thesis, 2022. http://hdl.handle.net/10362/135543.

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O SARS-CoV-2 é o vírus responsável pela atual pandemia COVID-19, que causou >400 mi-lhões de infeções e >5 milhões de mortes, a datar de Fevereiro de 2022. Apesar dos esforços de vacinação, continua a ser urgente desenvolver estratégias para controlar a infeção e tratar as pes-soas infetadas que apresentam sintomas. O SARS-CoV-2 é um vírus de RNA de sentido positivo que pertence à família Coronaviridae. A sua estrutura externa é esférica, sendo encapsulado por uma membrana viral e, de forma a infetar a célula hospedeira, precisa de fundir a sua membrana com a membrana desta célula. Uma das proteínas que está ligada à membrana viral do vírus é a proteína spike (S), que é composta por duas subunidades: S1, que contém um domínio de ligação ao recetor (RBD) respon-sável pela ligação ao recetor da célula hospedeira, e S2, que facilita a fusão membranar entre as membranas do vírus e da célula do hospedeiro. Assim, esta proteína é a principal responsável pela capacidade do vírus de entrar nas células hospedeiras, tornando-a num dos alvos terapêuticos mais promissores dos coronavírus. O objetivo deste trabalho era conceber e produzir proteínas antivirais que pudessem impedir a interação entre as duas proteínas e, assim, bloquear a infeção. Estas proteínas são concebidas para se ligarem à região do RBD e bloquear a sua interação com o recetor hospedeiro, a enzima conversora da angiotensina-2 (ACE2). Numa primeira etapa, várias proteínas antivirais foram computacionalmente concebidas com o programa Rosetta, com base nas interações entre a ACE2 e o domínio de ligação ao recetor da proteína S. Posteriormente, realizaram-se simulações de dinâmica molecular (MD) de três candida-tos, tanto livres em solução como em complexo com o RBD, a fim de testar a sua interação com esta proteína. Seguiu-se uma validação experimental que começou com a expressão e purificação dos três candidatos. Após a obtenção de frações puras, a estrutura secundária e a estabilidade tér-mica destas proteínas foram testadas, respetivamente, por espetropolarimetria de dicroísmo circular no UV distante e fluorimetria de varrimento diferencial. A fim de avaliar a afinidade de cada candida-to para com o RBD, foi utilizada a ressonância plasmónica de superfície. Finalmente, foram realiza-dos ensaios de neutralização para estudar a capacidade destas proteínas se ligarem ao RBD. Os resultados experimentais mostram que uma das proteínas concebidas representa uma estratégia terapêutica promissora que será ainda melhorada no futuro.
SARS-CoV-2 is the virus responsible for the current COVID-19 pandemic, which has caused >400 million infections and >5 million deaths, as of February 2022. Despite the vaccination efforts, it remains urgent to develop strategies to control the infection and treat patients. SARS-CoV-2 is a positive-sense RNA virus that is part of the Coronaviridae family. Its outer structure is spherical, it is encapsulated by a viral membrane and, in order to infect the host cell, it needs to fuse its membrane with the host cell membrane. One of the proteins that is attached to the viral membrane of the virus is the spike (S) protein, which is composed of two subunits: S1, containing a receptor binding domain (RBD) responsible for binding to the host cell receptor, and S2, that facilitates membrane fusion between the viral and host cell membranes. Thus, this protein is primarily responsible for the ability of the virus to enter the host cells, making it one of the most promising therapeutic targets of coronaviruses. The goal of this work was to design and produce antiviral proteins that might prevent the in-teraction between the two proteins and therefore block infection. These proteins are engineered to bind to the RBD region and block its interaction with the host receptor, the angiotensin converting enzyme-2 (ACE2). In a first step, several antiviral proteins were computationally designed with the Rosetta pro-gram, based on the interactions between ACE2 and the receptor-binding domain. Next, molecular dynamics (MD) simulations of three candidates were performed, both free in solution as well as in complex with the RBD, in order to test their interaction with the RBD. This was followed by experi-mental validation that began with the expression and purification of the three candidates. After ob-taining pure fractions, the secondary structure and thermal stability of these proteins were tested by far-UV circular dichroism spectropolarimetry and differential scanning fluorimetry, respectively. In order to assess the affinity of each candidate for the RBD, surface plasmon resonance was em-ployed. Finally, neutralization assays were performed to study the neutralization ability of the pro-teins. The experimental results show that one of the designed proteins is a promising therapeutic lead that will be further improved in the future.

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Malladi, Sameer Kumar. "HIV-1 and SARS-CoV-2 immunogen design." Thesis, 2020. https://etd.iisc.ac.in/handle/2005/5595.

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Human Immunodeficiency Virus (HIV-1) is the aetiologic agent of AIDS. Presently there are ~38 million HIV-1 infected individuals worldwide and ~1 million deaths in 2019. Since its discovery, the quest for vaccine candidate for HIV-1 is alive, yet no effective vaccine exists till date. HIV-1 viral displayed Envelope (Env) protein is the primary viral target of the humoral immune system and is thus an obvious vaccine candidate. The historic RV144 HIV-1 clinical trial resulted in a modest efficacy of the gp120 clade B/E vaccine candidate and renewed hope in finding a HIV-1 vaccine. However, monomeric gp120 does not induce protective antibodies and native-like trimeric Env was hypothesized to be a better candidate to induce broadly neutralizing antibodies. The recent structure of the BG505SOSIP.664 gp140 ectodomain reinvigorated interest in rational immunogen design. Chapter 1 outlines the HIV-1 virus, organisation, and structures of the Env ectodomain gp140, gp120, gp41 and various strategies to elicit neutralizing antibodies. Chapter 2 provides proof of principle of a method involving a computational sequence and structure guided Rosetta mutational scanning approach PROSS, to generate high yielding variants of the Env derivative gp140 without altering the trimeric structure and antigenicity. Chapter 3 utilizes the approach of cyclic permutation to rationally design trimeric gp120 derivatives that display a native V1V2 apex and retain binding to quaternary epitope directed bNAbs such as PGT145 and PGDM1400. Further, a nanoparticle display of the cyclic permutant was carried out to improve the immunogenicity of these potentially attractive vaccine candidates. Chapter 4 utilizes a structure guided approach to derive stable Env ectodomain variants by a cyclic permutation design strategy and describes an approach to engineer disulfides at the trimer Apex to covalently link the trimers for obtaining dynamically stable Env variants. HIV-1 Env displays conserved epitopes that are targeted by broadly neutralizing antibodies. CD4 binding site (CD4bs) antibodies are amongst the most potent. These CD4bs in humans are observed to be produced from a highly restricted set of germline sequences of the antibody repertoire. Chapter 5 attempts to utilize a structure guided approach to computationally design antibodies derived from novel germlines that are predicted to be energetically stable. Functional and biochemical characterization of these antibodies is reported Chapter 5. With the ongoing COVID-19 pandemic we attempted to develop a vaccine candidate utilizing a structure guided approach in Chapter 6. The Receptor binding domain (RBD) of the Spike protein of SARS-CoV-2 has been observed to be the primary target of the most potent neutralizing antibodies. Hence in Chapter 6 we designed an RBD subunit vaccine candidate to combat COVID-19. The designed RBD derivative is highly thermotolerant and also immunogenic and produces neutralizing antibodies comparable to several candidates currently being tested in the clinic.

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Madureira, Gonçalo Branco. "SARS-CoV-2 e Angiogénese: uma ligação por explicar." Master's thesis, 2021. https://hdl.handle.net/10216/134500.

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A nova doença do coronavírus 2019 (Covid-19) está associada a distúrbios multissistémicos, incluindo disfunção do sistema circulatório com disfunção endotelial, trombose microangiopática e inflamação angiocêntrica. Recentemente, a angiogénese intussusceptiva foi implicada na patogénese da doença. Neste artigo, revimos e discutimos amplamente os dados sobre a angiogénese intussusceptiva, incluindo mecanismos, drivers, reguladores e funções putativas. Revimos outras características angiogénicas relevantes na Covid-19, incluindo seu papel potencial na inflamação, disfunção endotelial e permeabilidade, bem como seu uso como prognóstico marcadores e funções terapêuticas. Concluímos que a divisão da angiogênese em Covid-19 é provavelmente o resultado de uma combinação de fatores. Propomos que a hipóxia, fatores induzíveis por hipóxia, bem como outros mediadores angiogénicos clássicos, como o Fator de crescimento endotelial vascular (VEGF) e via das angiopoietinas, hiperinflamação e tempestade e desregulação de citocinas do Sistema Renina-Angiotensina-Aldosterona interagem para promover a intussuscepção. No entanto, a angiogénese intussusceptiva permanece pouco compreendida e, portanto, mais estudos serão necessários para melhor caracterizar esse fenômeno. Também resumimos os principais dados sobre o uso de mediadores angiogênicos como ferramentas de prognóstico. Dados sugerem que as angiopoietinas e o VEGF estão elevados em pacientes com Covid-19 e são preditores de resultados adversos. Porém, esta é a primeira vez que se tenta relacionar esses achados à intussuscepção. Finalmente, revimos os escassos dados sobre mediadores angiogênicos como alvos terapêuticos em Covid-19. Esses descobertas preliminares sugerem um benefício potencial do bevacizumab como uma terapia complementar. Se isso se relaciona com intussuscepção ou não requer mais estudos.
: Novel Coronavirus Disease 2019 (Covid-19) is associated with multi-systemic derangement, including circulatory dysfunction with features of endothelial dysfunction, microangiopathic thrombosis and angiocentric inflammation. Recently, intussusceptive angiogenesis has been implicated in the pathogenesis of the disease. In this article, we have broadly reviewed and discussed data regarding splitting angiogenesis including mechanisms, drivers, regulators and putative roles. We have reviewed other relevant angiogenic features in Covid-19, including their potential role in inflammation, endothelial dysfunction and permeability as well as their use as prognostic markers and therapeutical roles. We conclude that splitting angiogenesis in Covid-19 is likely the result of a combination of factors. We hypothesize that hypoxia, hypoxia-inducible factors as well as other classic angiogenic mediators, such as the Vascular Endothelial Growth Factor (VEGF) and Angiopoietins pathway, hyperinflammation and cytokine storm and dysregulation of the Renin-Angiotensin-Aldosterone System interact to promote intussusception. However, splitting angiogenesis remains poorly understood and thus further studies are needed to better characterize this phenomenon. We have also summarized the main data regarding the use of angiogenic mediators as prognostic tools. Data suggests that angiopoietins and VEGF are elevated in Covid-19 patients and are predictors of adverse outcomes. However, this is the first time that an attempt to relate these findings to intussusception was made. Finally, we reviewed the scarce data regarding angiogenic mediators as therapeutic targets in Covid-19. These preliminary findings suggest a potential benefit of bevacizumab as an add-on therapy. Whether this relates to intussusception or not requires further studies.

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Martins, Cesariana Pryangka Viana. "Disinfection methods against SARS-CoV-2: a systematic review." Master's thesis, 2021. https://hdl.handle.net/10216/134388.

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O novo coronavírus SARS-CoV-2 é responsável pela mais recente pandemia que a humanidade enfrenta. Dada a sua elevada contagiosidade, tornou-se numa crise global causando milhões de mortes. Embora a vacinação já esteja disponível, um combate mais ativo desta pandemia necessita de outras abordagens preventivas. Este artigo pretende evidenciar os métodos mais eficazes de desinfeção do SARS-CoV-2 com base numa revisão sistemática de artigos publicados até à data. A pesquisa foi realizada na PubMed e na Web of Science e, de um total de 1229 artigos, 47 foram selecionados. A avaliação da qualidade dos referidos estudos foi efetuada pela OHAT risk of bias tool. Observaram-se métodos de desinfeção de superfícies em 20 estudos; destes, 14 trataram da descontaminação de PPEs; 11 estudos avaliaram métodos utilizados em superfícies biológicas e 4 analisaram métodos de desinfeção do ar. Assim, constatou-se que (1) a radiação UV-C, o ozono e revestimentos antimicrobianos demonstraram eficácia na desinfeção do SARS-CoV-2 de superfícies ambientais, por exemplo, em hospitais e lares; (2) a temperatura e a humidade relativa altas são fatores importantes na diminuição da carga viral; (3) a descontaminação dos PPEs pode ser feita de forma eficaz por calor, radiação UV-C ou peróxido de hidrogénio; (4) produtos contendo iodopovidona podem ter ação virucida na pele e nas membranas mucosas; (5) relativamente à higienização das mãos, soluções desinfetantes convencionais e outras contendo álcool demonstraram eficácia; (6) sistemas de ventilação com propriedades catalíticas, que recorram a radiação UV-C ou a sistemas de aquecimento, conseguem reduzir a carga viral presente no ar.
Background: The novel SARS-CoV-2 is responsible for the most recent pandemic faced by humanity. Given its contagious nature, SARS-CoV-2 has become a global crisis causing millions of deaths. Even though vaccination is already available, other effective preventive approaches and therapeutic drugs are still needed. Aim: This review highlights the up-to-date evidence found in literature of disinfection methods with efficacy against SARS-CoV-2. Methods: A research was conducted through PubMed and Web of Science to assess the disinfection methods used against SARS-CoV-2. From a total of 1229 studies found, 47 were included in this review. Quality assessment of the included records was evaluated by the OHAT risk of bias tool. Findings: Disinfection methods on environmental surfaces were approached by 20 studies. 14 studies demonstrated methods used to decontaminate PPEs. 11 articles addressed disinfection methods used on biological surfaces and 4 articles presented disinfection methods for airborne coronavirus. Conclusions: Several household and hospital disinfection agents, UV-C irradiation, ozone and surface coatings are effective in inactivating SARS-CoV-2 on environmental surfaces whereas high temperature and humidity are key factors in viral decay. The decontamination of PPEs can be conducted by heat treatment, UV-C irradiation and hydrogen peroxide vapor. Formulations containing povidone-iodine can provide virucidal action on the skin and mucous membranes. In the case of hand disinfection, typical soap bars and alcohols can inactivate SARS-CoV-2. Air filtration systems incorporated with materials that possess catalytic properties, UV-C devices and heating systems can effectively reduce airborne viral particles.

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46

Martins, Cesariana Pryangka Viana. "Disinfection methods against SARS-CoV-2: a systematic review." Dissertação, 2021. https://hdl.handle.net/10216/134388.

Full text

Abstract:

O novo coronavírus SARS-CoV-2 é responsável pela mais recente pandemia que a humanidade enfrenta. Dada a sua elevada contagiosidade, tornou-se numa crise global causando milhões de mortes. Embora a vacinação já esteja disponível, um combate mais ativo desta pandemia necessita de outras abordagens preventivas. Este artigo pretende evidenciar os métodos mais eficazes de desinfeção do SARS-CoV-2 com base numa revisão sistemática de artigos publicados até à data. A pesquisa foi realizada na PubMed e na Web of Science e, de um total de 1229 artigos, 47 foram selecionados. A avaliação da qualidade dos referidos estudos foi efetuada pela OHAT risk of bias tool. Observaram-se métodos de desinfeção de superfícies em 20 estudos; destes, 14 trataram da descontaminação de PPEs; 11 estudos avaliaram métodos utilizados em superfícies biológicas e 4 analisaram métodos de desinfeção do ar. Assim, constatou-se que (1) a radiação UV-C, o ozono e revestimentos antimicrobianos demonstraram eficácia na desinfeção do SARS-CoV-2 de superfícies ambientais, por exemplo, em hospitais e lares; (2) a temperatura e a humidade relativa altas são fatores importantes na diminuição da carga viral; (3) a descontaminação dos PPEs pode ser feita de forma eficaz por calor, radiação UV-C ou peróxido de hidrogénio; (4) produtos contendo iodopovidona podem ter ação virucida na pele e nas membranas mucosas; (5) relativamente à higienização das mãos, soluções desinfetantes convencionais e outras contendo álcool demonstraram eficácia; (6) sistemas de ventilação com propriedades catalíticas, que recorram a radiação UV-C ou a sistemas de aquecimento, conseguem reduzir a carga viral presente no ar.
Background: The novel SARS-CoV-2 is responsible for the most recent pandemic faced by humanity. Given its contagious nature, SARS-CoV-2 has become a global crisis causing millions of deaths. Even though vaccination is already available, other effective preventive approaches and therapeutic drugs are still needed. Aim: This review highlights the up-to-date evidence found in literature of disinfection methods with efficacy against SARS-CoV-2. Methods: A research was conducted through PubMed and Web of Science to assess the disinfection methods used against SARS-CoV-2. From a total of 1229 studies found, 47 were included in this review. Quality assessment of the included records was evaluated by the OHAT risk of bias tool. Findings: Disinfection methods on environmental surfaces were approached by 20 studies. 14 studies demonstrated methods used to decontaminate PPEs. 11 articles addressed disinfection methods used on biological surfaces and 4 articles presented disinfection methods for airborne coronavirus. Conclusions: Several household and hospital disinfection agents, UV-C irradiation, ozone and surface coatings are effective in inactivating SARS-CoV-2 on environmental surfaces whereas high temperature and humidity are key factors in viral decay. The decontamination of PPEs can be conducted by heat treatment, UV-C irradiation and hydrogen peroxide vapor. Formulations containing povidone-iodine can provide virucidal action on the skin and mucous membranes. In the case of hand disinfection, typical soap bars and alcohols can inactivate SARS-CoV-2. Air filtration systems incorporated with materials that possess catalytic properties, UV-C devices and heating systems can effectively reduce airborne viral particles.

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Madureira, Gonçalo Branco. "SARS-CoV-2 e Angiogénese: uma ligação por explicar." Dissertação, 2021. https://hdl.handle.net/10216/134500.

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A nova doença do coronavírus 2019 (Covid-19) está associada a distúrbios multissistémicos, incluindo disfunção do sistema circulatório com disfunção endotelial, trombose microangiopática e inflamação angiocêntrica. Recentemente, a angiogénese intussusceptiva foi implicada na patogénese da doença. Neste artigo, revimos e discutimos amplamente os dados sobre a angiogénese intussusceptiva, incluindo mecanismos, drivers, reguladores e funções putativas. Revimos outras características angiogénicas relevantes na Covid-19, incluindo seu papel potencial na inflamação, disfunção endotelial e permeabilidade, bem como seu uso como prognóstico marcadores e funções terapêuticas. Concluímos que a divisão da angiogênese em Covid-19 é provavelmente o resultado de uma combinação de fatores. Propomos que a hipóxia, fatores induzíveis por hipóxia, bem como outros mediadores angiogénicos clássicos, como o Fator de crescimento endotelial vascular (VEGF) e via das angiopoietinas, hiperinflamação e tempestade e desregulação de citocinas do Sistema Renina-Angiotensina-Aldosterona interagem para promover a intussuscepção. No entanto, a angiogénese intussusceptiva permanece pouco compreendida e, portanto, mais estudos serão necessários para melhor caracterizar esse fenômeno. Também resumimos os principais dados sobre o uso de mediadores angiogênicos como ferramentas de prognóstico. Dados sugerem que as angiopoietinas e o VEGF estão elevados em pacientes com Covid-19 e são preditores de resultados adversos. Porém, esta é a primeira vez que se tenta relacionar esses achados à intussuscepção. Finalmente, revimos os escassos dados sobre mediadores angiogênicos como alvos terapêuticos em Covid-19. Esses descobertas preliminares sugerem um benefício potencial do bevacizumab como uma terapia complementar. Se isso se relaciona com intussuscepção ou não requer mais estudos.
: Novel Coronavirus Disease 2019 (Covid-19) is associated with multi-systemic derangement, including circulatory dysfunction with features of endothelial dysfunction, microangiopathic thrombosis and angiocentric inflammation. Recently, intussusceptive angiogenesis has been implicated in the pathogenesis of the disease. In this article, we have broadly reviewed and discussed data regarding splitting angiogenesis including mechanisms, drivers, regulators and putative roles. We have reviewed other relevant angiogenic features in Covid-19, including their potential role in inflammation, endothelial dysfunction and permeability as well as their use as prognostic markers and therapeutical roles. We conclude that splitting angiogenesis in Covid-19 is likely the result of a combination of factors. We hypothesize that hypoxia, hypoxia-inducible factors as well as other classic angiogenic mediators, such as the Vascular Endothelial Growth Factor (VEGF) and Angiopoietins pathway, hyperinflammation and cytokine storm and dysregulation of the Renin-Angiotensin-Aldosterone System interact to promote intussusception. However, splitting angiogenesis remains poorly understood and thus further studies are needed to better characterize this phenomenon. We have also summarized the main data regarding the use of angiogenic mediators as prognostic tools. Data suggests that angiopoietins and VEGF are elevated in Covid-19 patients and are predictors of adverse outcomes. However, this is the first time that an attempt to relate these findings to intussusception was made. Finally, we reviewed the scarce data regarding angiogenic mediators as therapeutic targets in Covid-19. These preliminary findings suggest a potential benefit of bevacizumab as an add-on therapy. Whether this relates to intussusception or not requires further studies.

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Ferreira, Victor Leonel Vieira. "SARS-CoV-2 detection methods: where are we now?" Master's thesis, 2020. http://hdl.handle.net/10316/93052.

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Dissertação de Mestrado em Biotecnologia Farmacêutica apresentada à Faculdade de Farmácia
SARS-CoV-2 (Síndrome Respiratória Aguda Grave Coronavírus 2) é um coronavírus (CoVs) que pertence à família Coronaviridae e ao género Betacoronavirus, sendo considerado o maior grupo de vírus que causam infeções respiratórias e gastrointestinais em humanos e animais. Os primeiros casos da doença provocada pelo novo membro dos CoVs em humanos (Doença causada pelo Coronavírus 2019 (COVID-19)) surgiram em dezembro de 2019 na cidade de Wuhan, na China. SARS-CoV-2 é um vírus com uma maior capacidade de infeção em humanos, tendo por comparação outros CoVs do mesmo género já descobertos. Num curto período de tempo, este vírus causou milhares de infeções e mortes na China, e consequentemente, disseminou-se pelo mundo, sendo declarada a situação pandémica pela Organização Mundial da Saúde em março de 2020. Por falta de tratamentos específicos, vacinas e testes de deteção, a COVID-19 é um grande problema de saúde pública. Contudo, os métodos de deteção atualmente utilizados baseiam-se em métodos invasivos, nomeadamente a aplicação de zaragatoas no nariz ou na boca para retirar células da nasofaringe ou orofaringe, respetivamente. Nos últimos anos, o interesse por procedimentos minimamente invasivos tem crescido na medicina, o que levou a um maior sucesso das análises baseadas em fluidos biológicos, para diversas doenças e infeções. Ademais da nasofaringe e orofaringe, o vírus SARS-CoV-2 encontra-se principalmente no trato respiratório inferior. A deteção do vírus na saliva, fezes e urina tem sido reportada e, até o momento, não foi relatada nenhuma informação sobre qual amostra biológica permite maior sensibilidade. Além disso, é necessário estabelecer métodos mais adequados para a deteção de SARS-CoV-2 em indivíduos assintomáticos e/ou em fase pré-sintomática, os quais são mais adequados para estudos da população em geral.Neste trabalho reportamos as principais características do SARS-CoV-2 e da COVID-19 e analisamos os testes disponíveis para a deteção do SARS-CoV-2.
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a coronavirus (CoVs) that belongs to the family Coronaviridae and the genus Betacoronavirus, considered to be the largest group of viruses causing respiratory and gastrointestinal infections in humans and animals. The first cases of the disease caused by the new member of CoVs in humans (Coronavirus Disease 2019 (COVID-19)) appeared in December 2019 in the city of Wuhan, in China. SARS-CoV-2 is a virus with a higher human infection capacity, compared to other CoVs of the same genus already discovered. In a short time, this virus caused thousands of infections and deaths in China, and consequently, has been propagating throughout the world, being recognized a pandemic by the World Health Organization (WHO) on March of 2020. Owing to the lack of specific treatments, vaccines and screening methods, COVID-19 has become a major public health problem. However, detection methods currently used are based on invasive methods, namely the use of swabs through the nose or mouth to scrap cells from the nasopharynx or oropharynx, respectively. In recent years, the interest for minimally invasive procedures has grown in medicine, leading to greater success in the biological fluids-based evaluation, for several diseases and infections. Aside from the nasopharynx and oropharynx, the SARS-CoV-2 virus is found mostly in the lower respiratory tract. SARS-CoV-2 detection in saliva, stool and urine has been reported, and to this date, no data were disclosed about which biological sample allows higher sensitivity. Also, it is needed to establish the methods most suited for SARS-CoV-2 detection in asymptomatic individuals and/or at a presymptomatic stage, which are more suitable for population-wide studies.In this work, we review the key features of SARS-CoV-2 and COVID-19 and analyse the testing methods available to detect SARS-CoV-2 presence.

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Pereira, Maria Pacheco. "SARS-CoV-2: Comunicação de Risco e Crise em Emergência." Master's thesis, 2021. https://hdl.handle.net/10216/133200.

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Pereira, Maria Pacheco. "SARS-CoV-2: Comunicação de Risco e Crise em Emergência." Dissertação, 2021. https://hdl.handle.net/10216/133200.

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