Dissertations / Theses on the topic 'Virus SARS-CoV-2'
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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.
Full textDuring 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
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.
Full text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
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.
Full textAt 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
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.
Full textMaster 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.
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.
Full textThe 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
Mazzini, Livia. "VIRUS PANDEMICI EMERGENTI: VALUTAZIONE IMMUNOLOGICA DEL VIRUS INFLUENZALE A/VIETNAM/1194/2004 (H5N1) E DEL NUOVO SARS-COV-2." Doctoral thesis, Università di Siena, 2021. http://hdl.handle.net/11365/1126879.
Full textGruvnäs, 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.
Full textMarot, 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.
Full textAt 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
Decarreaux, Dorine. "Séroprévalence des IgG dirigées contre le SARS-CoV-2 dans une population universitaire et parmi des professionnels de santé en soins primaires et leurs contacts au sein des ménages." Electronic Thesis or Diss., Corte, 2024. http://www.theses.fr/2024CORT0007.
Full textThis thesis emerged in the context of the COVID-19 pandemic, shedding light on the challenges faced due to the novelty and complexity of the virus, and revealing major gaps in our knowledge. It focused on the academic community in Corsica and primary healthcare professionals in mainland France, considered potentially at risk. The underlying hypothesis is that these populations, due to their social interactions or high-risk professional environments, are likely to be more exposed to the virus compared to the general population. Thus, this thesis aimed to document the virus spread and immune responses within these populations.The main objectives of this thesis were, on one hand, to gather specific data for the Corsican region, focusing on estimating the seroprevalence of anti-SARS-CoV-2 IgG antibodies and analyzing the persistence of immune responses among students and staff at the University of Corsica, while identifying factors associated with the detection of these antibodies. On the other hand, it aimed to assess the seroprevalence of anti-SARS-CoV-2 IgG antibodies and infection prevalence among primary healthcare professionals in mainland France, as well as to determine factors associated with the detection of neutralizing antibodies and prior infection. To achieve these objectives, four main studies were conducted focusing on (i) seroprevalence and exposure factors to SARS-CoV-2 during the second wave among the Corsican university population, (ii) an eight-month serological follow-up of anti-SARS-CoV-2 IgG antibodies among the university population, (iii) seroprevalence and factors associated with neutralizing antibodies among primary healthcare professionals in mainland France after the third wave, and (iv) SARS-CoV-2 infection prevalence and factors associated with prior infection among these healthcare professionals.For the Corsican university population, the studies revealed a seroprevalence of 11.7%, significantly higher than that of the general Corsican population. Over 30% of participants who tested positive for the ELISA-S test were asymptomatic, highlighting the risk of silent transmission. Identified risk factors included place of residence, use of public transportation or carpooling, and contact with confirmed cases of COVID-19. Our results also underscored the importance of vaccination to bolster individual and collective immunity, notably observing antibody waning over time among some unvaccinated participants. For primary healthcare professionals in mainland France, the studies showed high seroprevalence of anti-S IgG antibodies (94.7%) and neutralizing antibodies (81.3%), mainly attributable to vaccination. Although they were not at higher risk of infection than the general population, about a quarter of them were infected at the time of the study, as evidenced by the 28.3% seroprevalence of anti-N IgG antibodies, highlighting their vulnerability. Significant variations were observed based on vaccination status and prior infection, demonstrating the importance of vaccination in boosting immune response and reducing infection risk. Factors associated with infection included geographical region of workplace, professional category, and unprotected contact with confirmed COVID-19 cases
Checa, Ruano Luis. "Structure-based design of antiviral drugs against respiratory viruses using in silico approaches." Electronic Thesis or Diss., Sorbonne université, 2024. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2024SORUS0743.pdf.
Full textProtein-Protein interactions (PPI) play crucial roles in many biological pathways and are being increasingly explored as potential therapeutic targets, including for treating infectious diseases. However, designing small molecule modulators for PPI remains challenging as PPI interfaces have not evolved to bind small molecules like conventional drug targets such as enzymes or membrane receptors. Therefore, proof of their druggability must be made on a case-by-case basis. In this context, computational approaches can be useful in assisting the design of PPI modulators.This work aims to develop new in silico drug design protocols specifically tailored to PPI targets, with the goal of designing new antiviral drugs against two PPI targets: the respiratory syncytial virus (RSV) and the SARS-CoV-2
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.
Full textUterine 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
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.
Full textWe 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
Aquino, Yann. "Bases génétiques et évolutives de la variabilité interpopulationnelle de la réponse immunitaire au SARS-CoV-2." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS488.
Full textHumans display substantial interindividual clinical variability after SARS-CoV-2 infection, the genetic and immunological basis of which has begun to be deciphered. However, the extent and drivers of population differences in immune responses to SARS-CoV-2 remain unclear. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells—from 222 healthy donors of diverse ancestries—that were stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces weaker, but more heterogeneous, interferon-stimulated gene activity compared with influenza A virus, and a unique pro-inflammatory signature in myeloid cells. Transcriptional responses to viruses display marked population differences, primarily driven by changes in cell abundance including increased lymphoid differentiation associated with latent cytomegalovirus infection. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell composition on population disparities in immune responses, with genetic variants exerting a strong effect on specific loci. Furthermore, we show that natural selection has increased population differences in immune responses, particularly for variants associated with SARS-CoV-2 response in East Asians, and document the cellular and molecular mechanisms by which Neanderthal introgression has altered immune functions, such as the response of myeloid cells to viruses. Finally, colocalization and transcriptome-wide association analyses reveal an overlap between the genetic basis of immune responses to SARS-CoV-2 and COVID-19 severity, providing insights into the factors contributing to current disparities in COVID-19 risk
Maguiña, Jorge L., Percy Soto-Becerra, Yamilee Hurtado-Roca, and Roger V. Araujo-Castillo. "Laboratory tests for identification of sars-cov-2 during pandemic times in Peru: Some clarification regarding «diagnostic performance»." Instituto Nacional de Salud, 2020. http://hdl.handle.net/10757/655698.
Full textLyrio, Ana Paula Batisti. "Desenvolvimento e implementação de equipamento para descontaminação de superfícies." Master's thesis, Universidade de Évora, 2021. http://hdl.handle.net/10174/30555.
Full textArotoma, De La Cruz Nahomy Lucía. "Medidas de protección según el antecedente de infección por SARS-CoV-2 en obstetras del Hospital Nacional Sergio E. Bernales, 2021." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2021. https://hdl.handle.net/20.500.12672/17113.
Full textBarrios, Cárdenas Pascual. "Resultados maternos y neonatales en puérperas reactivas y no reactivas SARS-COV-2 en el Hospital San Juan de Lurigancho, 2020." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2021. https://hdl.handle.net/20.500.12672/17216.
Full textLahmar, Imran. "Impact de la polarité et de la spécificité des lymphocytes T dans la protection contre l'infection par le SARS-CoV-2." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL067.
Full textThe COVID-19 pandemic caused by the SARS-CoV-2 virus has required a deep understanding of the immune response in order to develop effective prevention and treatment strategies. Early on, the scientific community demonstrated that humoral immunity induced by infection or vaccination could generate protective neutralizing antibodies against infection and disease severity in humans. However, it has been shown that the protection mediated by these antibodies diminishes rapidly over time, partly due to the escape of SARS-CoV-2 variants from their acquired neutralizing properties as well as the decrease in their concentration over time. It has also been demonstrated that vaccination and infection can induce cellular immunity mediated by T lymphocytes. This immunity seems to persists longer than humoral immunity and is believed to recognize different variants of SARS-CoV-2 more effectively. Experimental results in humans and animal models have suggested that this type of immunity could also play a complementary protective role to humoral immunity. However, the molecular characteristics of this protective cellular immunity have not yet been fully defined. Therefore, this thesis focused on the impact of the polarity and specificity of T lymphocytes on protection against SARS-CoV-2 infection. Firstly, we extensively characterized the polarity and the specificity of spontaneous or infection-induced cellular immune responses. Our results revealed that Th1 polarity was associated with protection against infection. Furthermore, we identified reactivities directed against the Receptor Binding Domain (RBD) as being most important in these protective responses. These findings laid the foundation for the development of a cellular test to monitor these protective immune responses on a large scale. Secondly, we examined the effect of vaccination on cellular immune response. We confirmed that the number of vaccinations was indeed capable of enhancing cellular immunity directed against RBD. We identified patients with malignant hematologic diseases as a vulnerable population in which cellular immune response was impaired despite vaccination. In this population, immune responses directed against the RBD region were highly significant for protection against infection. We also explored the evolution of the immune response over time and in relation to the number of vaccine doses administered. Our analyses revealed a decrease in interferon-gamma (IFN-y) concentrations over time, reaching a sustained stabilization, confirming the longevity of cellular responses. We also highlighted the evasion of the Omicron variant from the protection conferred by IFN-y secretion against RBD. This finding emphasized the urgent need for new biomarkers to evaluate the effectiveness of vaccination against the Omicron variant. In this context, we identified the chemokine CXCL10 as a potential marker of vaccine efficacy. In conclusion, this thesis has contributed to a better understanding of the immune response induced by SARS-CoV-2 and vaccines. The obtained results provide tools to guide vaccination policies and the development of new vaccines. Moreover, the identification of new biomarkers and the exploration of the polarity and specificity of T lymphocytes offer promising prospects for the development of personalized vaccines. These advancements are crucial in the fight against the COVID-19 pandemic and in preparing for future viral epidemics
Velasco, Kathleen Anne. "Ruolo potenziale del particolato atmosferico nella diffusione del SARS-COV-2 in Emilia-Romagna durante la seconda ondata: un'analisi dei dati." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amslaurea.unibo.it/23006/.
Full textMeunier, Thomas. "Étude des mécanismes d’action de nouveaux inhibiteurs de coronavirus humains." Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS057.
Full textCoronaviruses are enveloped RNA viruses infecting mammals and birds. Four coronaviruses causing mild diseases, like common cold, have been described in human, HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1. During the last two decades, three new, highly pathogenic coronaviruses have been identified the SARS-CoV (Severe Acute Respiratory Syndrom) in 2003, the MERS-CoV (Middle East Respiratory Syndrome) in 2012 and recently the SARS-CoV-2 in December 2019. The COVID-19 global outbreak caused by SARS-CoV-2, highlighted the lack of specific antiviral available against this family of virus. The team of Dr Karin SERON from the Cellular and Molecular Virology laboratory of the Center for Infection and Immunity of Lille, is specialized in the identification of antiviral compounds from natural origin. Indeed, plants are a source of natural therapeutic compounds and many plants are still being used in traditional medicine. The aim of my thesis was to identify natural antiviral agents against highly pathogenic human coronaviruses with the help of the knowledge and tools developed by the laboratory. My first project was carried out in collaboration with the group of Dr Simon Bordage from the Pharmacognosy laboratory of the Faculty of Pharmacy of Lille directed by Pr Sevser Sahpaz. Plant extracts from Ivorian plants used it traditional medicine were tested against the coronavirus HCoV-229E and we selected the most active, the Mallotus oppositifollius extract. After bio-guided fractionation, the active compound was isolated and characterized, the pheophorbide a (Pba). Pba is able to inhibit the infection of HCoV-229E and highly pathogenic coronaviruses MERS-CoV and SARS-CoV-2 (IC50 = 0.18 μM) as well as other enveloped viruses using a photo-dynamic inactivation mechanism. Pba targets the viral envelop and inhibits the fusion step. Pba is the first described natural antiviral against SARS-CoV-2 with direct photosensitive virucidal activity. This molecule could potentially be used in therapy or as disinfectant. My second project was about an anthocyanidin, the delphinidin, identified in the laboratory for its antiviral activity against hepatitis C virus. We showed that delphinidin is an entry inhibitor of coronaviruses in a dose-dependent manner for HCoV-229E, MERS-CoV and SARS-CoV-2 (IC50 = 16-20 μM). Our results show that delphinidin targets the glycosylation sites on the surface protein S. Thanks to a collaboration with the laboratory of Medicinal and Bioorganic Chemistry of Strasbourg, led by Dr Mourad Elhabiri, delphinidin synthetic derivates were screened in order to identify compounds with higher antiviral capacities. We thereby identify an active compound against HCoV-229E with a lower IC50 than delphinidin (IC50 = 0.06 μM). Surprisingly, its mechanism of action seems to be different than delphinidin with an activity at the replication step.In conclusion, during my thesis I was able to identify new natural antivirals against human coronaviruses, and in particular SARS-CoV-2, with novel mechanisms of action. This work may serve as a basis for obtaining molecules that can be used in the future for the treatment of coronavirus diseases
Leducq, Valentin. "Apport des outils de biologie moléculaire dans l'étude et la surveillance du SARS-CoV-2 au cours de la pandémie de COVID-19." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS203.
Full textFrom the onset of the COVID-19 pandemic, molecular biology tools for detection and analysis of the SARS-CoV-2 genome were developed and deployed on an unprecedented scale. PCR techniques have been used to diagnose millions of people on a daily basis, while the democratization of next-generation sequencing (NGS) has enabled the rapid generation of hundreds of thousands of viral genomes. These tools have been a major source of information in the study and understanding of the pathophysiology of SARS-CoV-2, but also in the real-time monitoring of the dynamics of the pandemic and the evolution of this virus. We undertook this thesis to evaluate how these molecular biology tools can contribute to the study and surveillance of SARS-CoV-2, in three studies with different objectives. With the PhyloCoV study, we first provided a precise description of the evolution of viral diversity observed during the year 2020 in the Ile-de-France area, thanks to the sequencing of 736 SARS-CoV-2 genomes from patients and healthcare workers of the Pitié-Salpêtrière and Bichat Claude-Bernard University Hospital. This study also allowed us to develop a phylogenetic clustering method allowing the detection of intra-hospital transmission of COVID-19. Then, in the framework of an observational study within the GH Sorbonne Université, we estimated the frequency and mortality associated with nosocomial transmissions of SARS-CoV-2. Between September and November 2020, 209 cases of nosocomial COVID-19 were identified, representing 13.9% of hospitalized patients infected with SARS-CoV-2 and associated with a mortality of 31%. Sequencing of the viral genomes disproved nearly one third of nosocomial transmissions and revealed valuable information about transmission routes within hospital wards. Finally, with the COCOPREV study, we studied the evolution of the SARS-CoV-2 genome during infection in patients treated with monoclonal antibodies, mostly immunocompromised. Several resistance mutations emerge in the SPIKE protein under the three treatments studied. Patients treated with Tixagevimab/Cilgavimab had a 5-fold increased risk of developing mutations at residues R346 and K444. Unlike other mutations found, R346 and K444 substitutions have repeatedly emerged in different variants due to their impact on SARS-CoV-2 fitness. They were finally selected by the currently dominant BQ.1 and XBB variants. In conclusion, we have demonstrated the utility of molecular biology tools in monitoring SARS-CoV-2 transmission in hospitals and the general population, as well as in identifying emerging resistance mutations in patients treated with monoclonal antibodies. These tools will most likely continue to be used in the context of the COVID-19 pandemic but also in monitoring the emergence and spread of other viruses
Cucho, Gamboa Grover Omar. "Verificación del desempeño analítico de la prueba Elecsys AntiSARS-CoV-2 para la detección cualitativa de anticuerpos en el analizador inmunológico automatizado Cobas e 411, Lima 2020." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2021. https://hdl.handle.net/20.500.12672/16408.
Full textAlejos, Tapia Renzo Carlos. "Utilidad de la tomografía con reconstrucción SAFIRE para la caracterización de lesiones pulmonares en pacientes infectados por SARS-COV2." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2022. https://hdl.handle.net/20.500.12672/17806.
Full textBrier, Lucile. "Conception d'une stratégie de découverte de composés antiviraux contre les coronavirus : du criblage à l'optimisation d'inhibiteurs de la protéase 3CL du SARS-CoV-2." Electronic Thesis or Diss., Université de Lille (2022-....), 2022. http://www.theses.fr/2022ULILS031.
Full textCoronaviruses are RNA viruses causing respiratory, enteric, hepatic and neurological diseases of varying severity in different species, including humans. Among them, seven can infect humans. HCoV-OC43, HCoV-NL63, HCoV-229E, and HCoV-HKU1 strains cause mild respiratory tract infections. SARS-CoV, MERS-CoV, and SARS-CoV-2 are potentially fatal and have caused major outbreaks. Today, SARS-CoV-2 is still circulating but the vaccine strategy has significantly reduced the risks of hospitalization and death. Also, the first specific antiviral drug has been authorized on the market (Paxlovid™). Nevertheless, coronaviruses are viruses with a high mutation and recombination rate, therefore the probability of facing new epidemics is very high. Thus, there is a need to discover new therapies to treat COVID-19 but also to anticipate and prevent future epidemics. Thanks to its essential role in the viral replication cycle of coronaviruses and the lack of human homolog, the viral protease 3CL is a promising target for the development of anti-coronaviral compounds. Moreover, this protease is remarkably conserved among coronavirus species. The 3CLpro is then an interesting target for the design of broad-spectrum antivirals able to fight against SARS-CoV-2 but also against potential emerging coronaviruses. Thus, the objective of this thesis work was to develop a strategy to discover new non-peptidomimetic inhibitors of the 3CLpro of SARS-CoV-2 that are potent, selective and capable of exerting pan-inhibition on other coronavirus species. The first part of this thesis project consisted of developing and performing a high-throughput screening on the SARS-CoV-2 3CL protease, allowing the identification of several chemical series of interest. Further work focused on the optimization of two chemical series, reversible covalent inhibitors for the first one and non-covalent for the second one, whose chemotypes have not been described on the 3CL protease. In these two chemical series, more than 90 analogues have been synthesized with the aim of improving the potency on the target and establishing structure-activity relationships. Physicochemical and ADME properties in vitro, binding mode, selectivity towards human proteases, inhibition of 3CLpro from other coronaviruses and in cellulo antiviral activity were studied
Fahey, Nisha. "Epidemiology and Characteristics of Pediatric COVID-19 Cases Among UMass Memorial Health Care Patients." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1140.
Full textMatteo, Broketa. "Identification des répertoires d'affinité des cellules sécrétrices d'anticorps." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS616.
Full textThis research aimed to explore the complexities of antibody affinities of antibody-secreting cells (ASCs) in the context of both vaccination and autoimmune responses. The first aim was to characterize the ASC response to mRNA vaccination against SARS-CoV-2. The advent of novel mRNA vaccines to tackle the COVID-19 pandemic presented a unique opportunity to study a novel humoral B cell response post-immunization. We used a droplet microfluidic assay, DropMap, able to measure single cell antibody secretion and affinity towards antigen to characterize at high throughput the functional characteristics of ASCs in the weeks and months following mRNA vaccine administration, with a distinction made between individuals based on prior SARS-CoV-2 infection. Our characterization of the ASC response to mRNA vaccination against SARS-CoV-2 has provided valuable insights into how B cells respond to novel vaccines and affinity repertoires during human vaccination. The second aim was to measure the affinity repertoires of a non-natively secreting B cell population, memory B cells (Bmem), following mRNA vaccination against SARS-CoV-2. This involved characterizing the affinity repertoires of Bmem-derived antibodies towards numerous SARS-CoV-2 receptor-binding domain (RBD) variants by implementing a high throughput screening system based on biolayer interferometry (BLI) measurements. The third aim was to develop a novel technique (termed DropPick) for recovering cells of interest from DropMap. DropMap is a potent technique for direct identification of ASCs and affinity characterization. However, there is much more to be discerned from analyzing these cells of interest using additional methods, such as flow cytometry for phenotyping or B cell receptor sequencing for clonal analyses and re-expression. My thesis work has shown that after receiving the BNT162b2 vaccine targeting the Hu-1 SARS-CoV-2 Spike protein, high-affinity plasmablasts were initially induced targeting both the Hu-1 and Omicron Spike RBD variants but exhibited a rapid decline. Surprisingly, plasmablasts with low affinity consistently constituted more than 65% of the specific plasmablast response at all observed time points. Our high throughput BLI affinity measurements on Bmem antibodies from similarly vaccinated individuals found high affinity clones against several RBD variants with signs of affinity maturation; comparing results between variants allowed for key antibody binding epitopes to be determined. Following this cohort of Bmem antibodies also found that viral evolution to the Omicron RBD variant resulted in a large evasion of Bmems mutated towards Hu-1 RBD with high affinity, with especially high evasion of potently Hu-1 and Beta neutralizing antibodies. In parallel, I have developed a system to label cells of interest using photoactivatable markers within DropMap and the technical platform to achieve targeted cell photoactivation by targeted UV illumination. This involved the creation of automated programs for DropMap assay real-time analyses as well as macro control of microscope utilities to deliver discrete illumination to droplets. I have also shown the ability for this workflow to yield a clear population by flow cytometry with up to 70% efficiency, with the potential for sorting and future downstream analyses. These results will aid ongoing efforts to understand the role of affinity in ASC responses and their immune contexts. Our data provide broad affinity repertoires that provide valuable functional insights into B cell responses to SARS-CoV-2 and mRNA vaccination. The development of the DropPick platform has shown the potential to further leverage these studies to collect molecular data from specific functional subsets
Colosi, Elisabetta. "Modélisation de la propagation de COVID-19 dans les établissements scolaires afin de maintenir l'apprentissage en personne en toute sécurité." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS416.pdf.
Full textWhen COVID-19 emerged as a global pandemic in March 2020, schools were among the first settings to be closed to curb the transmission of SARS-CoV-2. However, the choice of closing school for a relatively long time was quite controversial and largely debated, especially for the harmful effects on students’ well-being and learning development. Therefore, governments worldwide gradually reintroduced in-person activities in schools, implementing various control measures to manage positive cases. The approaches taken by different countries varied, with some adopting reactive strategies in response to confirmed cases, while others implemented more proactive measures as the pandemic progressed. Schools remained vulnerable environments, especially in the absence of vaccination for younger students and the emergence of more contagious variants such as Delta and Omicron. In this thesis, I estimated the transmissibility of SARS-CoV-2 within schools for different variants and evaluated a range of testing and screening strategies to provide safe options for keeping schools open while minimizing educational disruption. To achieve this aim, I developed an agent-based model to simulate SARS-CoV-2 spread through face-to-face interactions among students and teachers in a primary and secondary school in France under different epidemic contexts. I fitted the model to the student prevalence data gathered from pilot and experimental screening campaigns conducted in specific pandemic phases, from the emergence of the Alpha variant in 2021 to the Omicron variant in early 2022 in France. I thus estimated the effective reproductive number in both schools and the contribution of school-based transmission to the overall spread in children. I then assessed the effectiveness of different intervention protocols in limiting importation and onward transmission, reducing school absence, and optimizing testing resources through a cost-benefit analysis. The results contained in this dissertation shed light on the role of school contacts as a potential source of renewed transmission during the COVID-19 pandemic, showing that transmission in schools represented a considerable contribution. According to our results, regular screening with large enough adherence can reduce cases and absences even under high-incidence conditions, as experienced during the Omicron wave of early 2022. The higher effectiveness achieved by weekly screening compared to reactive strategies is also confirmed by our retrospective analysis of a real-world experiment in a selected number of French primary schools during the Delta and Omicron waves between the end of 2021 and the beginning of 2022. Although COVID-19 no longer represents a global emergency, it will continue to circulate with other seasonal respiratory viruses (i.e., influenza, Respiratory Syncytial Virus, etc.) in children during the winter. The modelling framework developed in this thesis is well-suited for studying the transmission of respiratory viruses in densely populated settings, such as schools, quantifying the extent, and evaluating the impact of potential mitigation measures in the future
Custodio, Cuzcano Dante Miguel. "Factores sociodemográficos relacionados a la clasificación CORADS en pacientes con diagnóstico de SARS-CoV-2 que acuden al servicio de Tomografía Computada de una clínica privada, Lima. Marzo – julio 2020." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2021. https://hdl.handle.net/20.500.12672/17096.
Full textBarthelemy, Johanna. "Infections virales respiratoires et tissus adipeux blancs : Exemple de la grippe et de la COVID-19." Thesis, Université de Lille (2022-....), 2022. http://www.theses.fr/2022ULILS009.
Full textRespiratory viral infections remain a major public health issue, worldwide. This is particularly the case with flu, caused by influenza viruses, and COVID-19, an emerging infectious disease caused by the SARS-CoV-2 virus. Importantly, the populations most at risk of developing severe forms of flu or COVID-19 are obese individuals and the elderly. Although obesity and aging are both associated with major functional alterations of the white adipose tissue, the latter's involvement in the pathophysiology of influenza or COVID-19 remains poorly studied. The thesis project falls within this general theme.Recent work by our team has shown, in mice, that infection with the influenza virus causes metabolic reprogramming of the subcutaneous fat depots, mainly characterized by the browning of the tissue: a phenomenon which corresponds to the emergence of beige adipocytes with increased thermogenic activity. During my PhD, using complementary experimental in vivo, in vitro, ex vivo and in silico approaches, we showed that the response to influenza-infection-induced endoplasmic reticulum stress, and more specifically the PERK signaling pathway, is involved in white adipose tissue browning. Besides identifying a novel molecular mechanism that regulates thermogenesis, our work further specifies the role of the white adipose tissue in influenza infection.In parallel, we studied the impact of infection with the SARS-CoV-2 virus on the white adipose tissues of young adult and old hamsters - a preclinical model of COVID-19 recently implemented in our team. Our results showed that the infection is more severe - in terms of morbidity and mortality - in older animals than in young adults. Histomorphometric analysis of subcutaneous and visceral white adipose tissues showed that infection with SARS-CoV-2 is associated with a decrease in the size of adipocytes in these two depots; an effect that persists only in the older animals. Remarkably, the histological analysis of the tissues reveals the presence of numerous and large areas of adipocyte necrosis (resembling the “crown-like structures” that can be observed in white adipose tissues in the context of obesity) only in the subcutaneous fat depots of the older animals, even at distance from infection. As such, our study confirms and strengthens the most recent data in the literature, which describes a major role of the white adipose tissue in the pathophysiology of COVID-19
Al, Ibrahim Malak. "Anti-coronavirus potential of halophytes and invasive plants from Northern France : discovery of active terpenoids from Hippophae rhamnoides and Senecio inaequidens." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS003.
Full textCoronaviruses are responsible for mild to severe respiratory tract illnesses in humans. Despite significant advancements in understanding coronavirus pathology and clinical management, these viral diseases remain a public health concern due to recurrent outbreaks driven by the emergence of variants, unequal access to COVID-19 treatments, inadequate vaccination rates and untreated high-risk populations. Thus, it is imperative to proactively develop specific and affordable antiviral solutions to control and prevent future pandemics. Plants exposed to abiotic stress factors and new environments represent a vast source of bioactive compounds. In this project, we investigated the antiviral potential in vitro of different halophytes, less salt-tolerant plants and invasive plants collected in the North of France against different coronaviruses.In the first part of the project, a variety of strictly halophytes and relatively salt-tolerant plants growing on the coastline in northern France were screened for their in vitro antiviral activity against different coronaviruses. The most active plant species, Hippophae rhamnoides L. (Eleagnaceae), underwent bioguided fractionation to identify active natural products. Six compounds were isolated from the three most active fractions using preparative HPLC and were identified as cinnamoyl triterpenoids through HRMS and mono- and bi-dimensional NMR. Infection tests demonstrated a dose-dependent inhibition of these triterpenes against HCoV-229E and SARS-CoV-2, notably highlighting their activity against both viruses.In the second part of the project, the antiviral potential against coronaviruses of Senecio inaequidens (Asteraceae), an invasive plant species, was explored. Six compounds purified by CPC and preparative HPLC were identified as sesquiterpenoid derivatives. They displayed a dose-dependent inhibitory effect on HCoV-229E and four of them also exhibited inhibition against SARS-CoV-2.Our findings suggest that Hippophae rhamnoides and Senecio inaequidens could represent potential sources of antiviral agents against human coronaviruses
Silverstein, Noah J. "Disease Tolerance, Epigenetic Inheritance, and Surviving Pathogenic Viral Infections." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1149.
Full textHognon, Cecilia. "Modélisation et simulation moléculaire pour la compréhension des processus biologiques fondamentaux et le développement de nouveaux agents thérapeutiques contre le cancer et la Covid-19." Electronic Thesis or Diss., Université de Lorraine, 2021. http://www.theses.fr/2021LORR0233.
Full textDuring this Ph.D. thesis I have used state-of-the-art molecular modeling and simulation techniques to answer to key biological questions related to the fundamental bases of cancer development and to the mechanisms of viral replication and diffusion, including those of SARS-CoV-2. In addition to rationalize the molecular bases behind critical biological outcomes, including also the assessment of the thermodynamic properties of key biological aggregates, I have also studied the possible rational molecular design of novel therapeutic agents acting as antiviral and anticancer. To this end I have studied the induction and reparation of DNA lesions, as well as the basis of genome organization and DNA compaction. This has also brought me to take into accounts epigenetic regulation, the possible design of external agents perturbing gene expression, and the regulation of signaling pathways such as iron homeostasis. Furthermore, I have studied key viral components of SARS-Cov-2 including the spike protein, some non structural proteins such as the SARS Unique Domain, and the organization of its genome, for the formation of guanine quadruplexe sequences. Furthermore, I have also been interested in the understanding of immune system response, and in particular on the effects of variants on the human STING protein, which is able to sense the presence of endogenous genetic material and triggers the appropriate immune response. From a methodological point of view the use of multiscale approach, combining in some instance classical and QM/MM methods have shown its power in rationalizing not only chemical but biological effects and has paved the way to stronger rational design strategies
Bost, Pierre. "Decoding cellular communications and interactions between immune cells by using single-cell approaches." Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS020.pdf.
Full textCellular communications are essential to the proper functioning of multi-cellular organisms, particularly in order to adapt to a constantly changing environment. The cells of the immune system are no exception to this rule, but the interactions between immune cells remain little known and complicated to study. The recent emergence of 'single cell' sequencing technologies represents a unique opportunity to study these communications. In this thesis, different experimental and analytical approaches have been developed to study these communications on a single cell scale. These strategies were then applied to different disease contexts, including COVID-19, Alzheimer's disease or immunisation with inactivated pathogens, and identified previously unknown or poorly understood cellular communication pathways. However, the effectiveness of these approaches is limited by the lack of information on cell location and further work integrating such data will be essential to go further in the dissection of immune cell communications
Labbé, Vincent. "Risques thrombotiques et hémodynamiques chez les patients hospitalisés en réanimation présentant une fibrillation atriale de novo au cours d’un sepsis : caractérisation, stratification et stratégies thérapeutiques." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS556.pdf.
Full textObjectives Patients admitted to intensive care units with sepsis are at high risk of thrombotic events (TEs) throughout the circulatory systems (systemic, coronary, and pulmonary). We aimed to investigate the thrombotic risk during sepsis (i) within the systemic circulation in patients with new-onset atrial fibrillation (NOAF), (ii) within the coronary circulation in patients with acute myocardial infarction (MI), and (iii) within the pulmonary circulation in patients with severe COVID-19. Furthermore, while the risk of TE raises the question of whether thromboprophylaxis doses should be escalated, assessment of associated bleeding risk should be systematic in order to establish the benefit/risk balance of such treatment. Methods We investigated the risk of major cardiovascular events (risk characterization and stratification), including AT, major bleeding and death in three populations of septic patients with NOAF, MI or severe COVID-19 by studying (i) markers such as left atrial dysfunction on transesophageal echocardiography (TEE) and cardiac troponin, and (ii) thrombotic and hemorrhagic risk scores used in cardiology patients. We conducted a practice survey on thrombotic risk management in patients with de NOAF during sepsis. Finally, we carried out two therapeutic trials: the CAFS (Control Atrial Fibrillation Sepsis) multicenter, randomized, controlled superiority trial comparing three usual strategies to prevent hemodynamic risk with NOAF during septic shock (currently being included), and the ANTICOVID (ANTIcoagulation in patients with hypoxemic COVID-19 pneumonia) multicenter, randomized, controlled superiority trial comparing three anticoagulation strategies with dose escalation in patients with hypoxemic COVID-19 pneumonia Results Our work confirmed the high risk of major cardiovascular events during sepsis. In patients with NOAF, cardiological approaches to thrombotic (TEE abnormalities, CHA2DS2-VASc score) and hemorrhagic (HAS-BLED score) risk stratification seem limited. An individualized approach with TEE based on the CHA2DS2-VASc score could nevertheless be of interest. This work also better characterized the risk of intra-cardiac thrombus formation (absence of thrombus within 48 h of AF onset, low prevalence of post-cardioversion left atrial stunning). Finally, we confirmed the heterogeneity of hemodynamic and thrombotic risks management, calling for randomized trials. In patients with MI during sepsis, cardiological approaches to thrombotic risk stratification (GRACE and TIMI scores) also appear limited. In usual practice, an invasive strategy involving early coronary revascularization is very uncommon. In patients investigated using coronary angiography, the incidence of obstructive coronary artery disease is high. In patients with hypoxemic COVID-19 pneumonia, high-dose prophylactic anticoagulation, provided a better net clinical benefit driven by a 4-fold reduction in de novo thrombosis rate with no increase in major bleeding compared with standard-dose prophylactic anticoagulation. Also, therapeutic anticoagulation did not provide additional benefit in comparison with high-dose prophylactic anticoagulation. Conclusions On the basis of the common pro-thrombotic pathophysiology described in septic conditions, our work has made it possible to (i) better characterize clinical situations at particularly high thrombotic risk (NOAF, MI, severe COVID-19 infection), (ii) develop individual therapeutic strategies for thrombotic risk prevention (COVID-19), and (iii) establish the basis for subsequent trials in specific intensive care populations at very high thrombotic risk
Esteves, Souza Jerónimo, and Ríos Joaquín Javier Vela. "Efectos de una pandemia en los mercados de valores de renta variable: comparativa entre la Influenza de tipo A(H1N1) durante el periodo 2009- 2010 y el COVID-19 en el año 2019- 2020." Bachelor's thesis, Pontificia Universidad Católica del Perú, 2020. http://hdl.handle.net/20.500.12404/18466.
Full textAfter the pandemic better known as the Spanish flu of 1918, there was no other capable of putting the world economy, especially the stock markets of all countries, in serious trouble until the arrival of the new SARS-COV2 coronavirus, also called COVID19. For this reason, the present research seeks to analyze and compare the effects of two pandemics that occurred in the 2008-2020 period in the equity markets. These pandemics are influenza A (H1N1) that occurred in the 2009-2011 period and the new SARS-COV2 coronavirus that started in late 2019 in Wuhan, China. The analysis period for SARS-COV2 will be 2009-2020. It is proposed that for the Stock Exchanges of developed countries (USA, China and Spain) there will be a negative impact on the performance associated with these exchanges in the presence of COVID-19 in the short and medium term; this in turn will unleash a similar or even greater chain effect on the Stock Exchanges of the countries that make up the MILA (Latin American Integrated Market) Peru, Chile and Colombia. This impact would be of a larger scale than the impact caused by influenza A (H1N1) pdm09, because it is considered that the international financial crisis of 2008 was the determinant of the fall of the stock markets of the United States, Spain and developing countries in that period. In this research, a Panel Least Squares model will be used to estimate the effects of pandemics on the performance indexes of the mentioned countries.
Malladi, Sameer Kumar. "HIV-1 and SARS-CoV-2 immunogen design." Thesis, 2020. https://etd.iisc.ac.in/handle/2005/5595.
Full textPiçarra, Patricia Alexandra Jacinto. "Internship Reports and Monograph entitled "Virus-like particles based vaccines and their role in the COVID-19 pandemic”." Master's thesis, 2021. http://hdl.handle.net/10316/99021.
Full textEste trabalho de Final de Mestrado engloba os Relatórios de Estágio e Monografia Intitulada "Virus-like particles based vaccines and their role in the COVID-19 pandemic". No final de 2019, na China, um novo coronavírus foi identificado com o surgimento de uma pneumonia atípica. O mundo rapidamente ficou em alerta devido à alta velocidade com que este vírus se transmitia em todo o mundo. Este novo surto foi rapidamente declarado como uma pandemia.Desde o início surgiu a necessidade de criar uma vacina capaz de acabar com o pesadelo da pandemia.Diversas plataformas foram testadas para o desenvolvimento de vacinas contra a Síndrome Respiratória Aguda Grave Coronavirus 2 (SARS-COV-2), entre as quais vacinas que se baseiam em partículas semelhantes a vírus (VLP). As VLPs, que contam com alguns exemplos já existentes no mercado, como as vacinas para hepatite B e para o vírus do papiloma humano, são nanopartículas com base em proteínas que mimetizam a conformação do vírus, apresentando epítopos à superfície. As vacinas baseadas em VLPs já demonstraram ter inúmeras vantagens, incluindo o facto de serem seguras, não conterem o material genético do vírus e serem muito eficientes em termos de ativação do sistema imunológico. Apesar disso, na formulação destas vacinas muitas vezes aparecem associados adjuvantes.O conhecimento da estrutura do vírus SARS-COV-2 possibilitou o desenvolvimento de partículas que mimetizam este coronavírus.Pelo menos cinco vacinas de VLPs contra o SARS-COV-2 já estão em ensaios clínicos e apresentam potencial para serem bem-sucedidas.Neste texto de revisão, iremos reconhecer o potencial destas partículas que mimetizam os vírus, como elas ativam o nosso sistema imunológico, e desvendar os avanços que as vacinas baseadas em VLPs estão a ter nesta luta que o mundo está a enfrentar contra o COVID-19.Naturalmente, para isso temos que descobrir como funciona este vírus mortal.
This Master's Degree document comprises the Internship Reports and Monograph Entitled "Virus-like particles based vaccines and their role in the COVID-19 pandemic".In late 2019, in China, a new coronavirus was identified with the emergence of an atypical pneumonia. The world quickly became in alert due to the high speed with which this virus was being transmitted throughout the world. This new outbreak was quickly declared as a pandemic.From the outset the need arose to create a vaccine capable of putting an end to the pandemic nightmare.Several platforms were tested for the development of vaccines against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), among which virus like particle (VLP) based vaccines. VLPs, with some examples already on the market such us the vaccines for the hepatitis B and for human papilloma virus, are protein-based nanoparticles that mimic the conformation of the virus, presenting epitopes on their surface. VLP based vaccines have already been shown to have numerous advantages, including the fact that they are safe, do not contain virus genetic material, and very efficient in terms of activating immune system. Despite that, in the formulation of these vaccines they often appear associated with adjuvants. The knowledge of the structure of the SARS-COV-2 has made it possible for the development of particles that mimic these coronavirus.At least, five SARS-COV-2 VLP vaccines are already in clinical trials, and show potential to be successful.In this review text we will recognize the potential of these particles that mimic viruses, and how they activate our immune system, and unravel the advances that VLP based vaccines are having in this fight that the world is facing with the COVID-19. Naturally, for that we have to find out how this deadly virus works.
Costa, Maria Gabriela Meneses. "Relatório de Estágio e Monografia intitulada" Organoides Cerebrais na Modelação de Doenças Degenerativas e Infeciosas." Master's thesis, 2021. http://hdl.handle.net/10316/99162.
Full textO presente documento redigido no âmbito da Unidade Curricular “Estágio Curricular” do Mestrado Integrado em Ciências Farmacêuticas da Faculdade de Farmácia da Universidade de Coimbra inclui dois relatórios de estágio e uma monografia. Os relatórios de estágio, que seguem uma estrutura de análise SWOT (Strengths, Weaknesses, Opportunities and Threats), incidem sobre os estágios realizados na Indústria Farmacêutica Bluepharma Indústria Farmacêutica, S.A e em Farmácia Comunitária, na Farmácia Santiago, em Góis. A monografia, intitulada “Organoides Cerebrais na Modelação de Doenças Degenerativas e Infeciosas”, sintetiza os principais avanços científicos e direções futuras dos mais recentes modelos de estudo da fisiologia cerebral, os organoides cerebrais, expondo o conhecimento atual, descoberta, metodologias de obtenção, aplicação e principais desafios inerentes à técnica. De modo particular, destaca a modelação de doenças neurológicas como a Doença de Alzheimer, para exemplo de uma doença degenerativa, e infeção pelo vírus Zika e pelo vírus SARS-CoV2. Os organoides cerebrais são culturas tridimensionais in vitro que representam uma ferramenta de última geração para diagnósticos preditivos, compreensão fisiopatológica e desenvolvimento de terapias individualizadas, principalmente quando otimizados com o conhecimento de outras áreas científicas. Este documento conclui o ciclo de estudos com o trabalho realizado durante o último semestre do Mestrado Integrado em Ciências Farmacêuticas.
This document written within the "Curricular Internship" of the Integrated Master’s Degree in Pharmaceutical Science of the Faculty of Pharmacy, University of Coimbra includes of two internship reports and a monograph.The internship reports, which follow a SWOT analysis structure (Strengths, Weaknesses, Opportunities and Threats), focus on the internships carried out at the Pharmaceutical Industry Bluepharma Indústria Farmacêutica, S.A. and at Community Pharmacy,at the Farmácia Santiago, in Góis. The monograph, entitled "Brain Organoids in Modeling Degenerative and Infectious Diseases", summarizes the main scientific advances and future directions of the most recent models for the study of brain physiology, the brain organoids, exposing current knowledge, discovery, methodologies for obtaining, application, and main challenges inherent to the technique. In particular, the monograph highlights the modeling of neurological diseases such as Alzheimer's Disease, as an example of a degenerative disease, and infection by the Zika virus and by the SARS-CoV2 virus. Brain organoids are three-dimensional in vitro cultures that represent a state-of-the-art tool for predictive diagnoses, pathophysiological understanding and development of individualized therapies, especially when optimized with knowledge from other scientific areas. This document summarizes the end of this these studies with the work carried out during the last semester of the Integrated Master in Pharmaceutical Sciences.
Costa, Maria Gabriela Meneses. "Relatório de Estágio e Monografia intitulada" Organoides Cerebrais na Modelação de Doenças Degenerativas e Infeciosas." Master's thesis, 2021. http://hdl.handle.net/10316/99172.
Full textO presente documento redigido no âmbito da Unidade Curricular “Estágio Curricular” do Mestrado Integrado em Ciências Farmacêuticas da Faculdade de Farmácia da Universidade de Coimbra inclui dois relatórios de estágio e uma monografia. Os relatórios de estágio, que seguem uma estrutura de análise SWOT (Strengths, Weaknesses, Opportunities and Threats), incidem sobre os estágios realizados na Indústria Farmacêutica Bluepharma Indústria Farmacêutica, S.A e em Farmácia Comunitária, na Farmácia Santiago, em Góis. A monografia, intitulada “Organoides Cerebrais na Modelação de Doenças Degenerativas e Infeciosas”, sintetiza os principais avanços científicos e direções futuras dos mais recentes modelos de estudo da fisiologia cerebral, os organoides cerebrais, expondo o conhecimento atual, descoberta, metodologias de obtenção, aplicação e principais desafios inerentes à técnica. De modo particular, destaca a modelação de doenças neurológicas como a Doença de Alzheimer, para exemplo de uma doença degenerativa, e infeção pelo vírus Zika e pelo vírus SARS-CoV2. Os organoides cerebrais são culturas tridimensionais in vitro que representam uma ferramenta de última geração para diagnósticos preditivos, compreensão fisiopatológica e desenvolvimento de terapias individualizadas, principalmente quando otimizados com o conhecimento de outras áreas científicas. Este documento conclui o ciclo de estudos com o trabalho realizado durante o último semestre do Mestrado Integrado em Ciências Farmacêuticas.
This document written within the "Curricular Internship" of the Integrated Master’s Degree in Pharmaceutical Science of the Faculty of Pharmacy, University of Coimbra includes of two internship reports and a monograph.The internship reports, which follow a SWOT analysis structure (Strengths, Weaknesses, Opportunities and Threats), focus on the internships carried out at the Pharmaceutical Industry Bluepharma Indústria Farmacêutica, S.A. and at Community Pharmacy,at the Farmácia Santiago, in Góis. The monograph, entitled "Brain Organoids in Modeling Degenerative and Infectious Diseases", summarizes the main scientific advances and future directions of the most recent models for the study of brain physiology, the brain organoids, exposing current knowledge, discovery, methodologies for obtaining, application, and main challenges inherent to the technique. In particular, the monograph highlights the modeling of neurological diseases such as Alzheimer's Disease, as an example of a degenerative disease, and infection by the Zika virus and by the SARS-CoV2 virus. Brain organoids are three-dimensional in vitro cultures that represent a state-of-the-art tool for predictive diagnoses, pathophysiological understanding and development of individualized therapies, especially when optimized with knowledge from other scientific areas. This document summarizes the end of this these studies with the work carried out during the last semester of the Integrated Master in Pharmaceutical Sciences.
Gutiérrez, Laura. "Evaluación del desempeño analítico de dos ensayos inmunológicos de diferente configuración para la detección de anticuerpos anti SARS-CoV-2." Doctoral thesis, 2021. http://hdl.handle.net/11086/21904.
Full textCalcular la sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo de dos ensayos inmunológicos de diferente configuración (CMIA y ELISA) para la detección de anticuerpos anti SARS CoV 2 Evaluar la concordancia analítica entre los diferentes ensayos.
2023-11-30
Fil: Gutiérrez, Laura. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Barbás, María G. Gobierno de la Provincia de Córdoba. Ministerio de Salud. Laboratorio Central; Argentina.
Raheja, Harsha. "Deciphering the role of host protein HuR in RNA virus life cycle and pathogenesis: Hepatitis C Virus and SARS-CoV-2 as exemplars." Thesis, 2023. https://etd.iisc.ac.in/handle/2005/6167.
Full textCSIR-SPM
Jesus, Ana Rita Moreira Gaspar de. "O Processo de Desenvolvimento e Aprovação de Medicamentos: O Caso Particular das Vacinas COVID-19." Master's thesis, 2021. http://hdl.handle.net/10316/99135.
Full textUm novo medicamento está sujeito a um rigoroso processo de investigação, desenvolvimento, avaliação e aprovação, por forma a garantir a sua qualidade, segurança e eficácia e o cumprimento dos requisitos exigidos pelas entidades regulamentares competente. No final do ano de 2019, foi identificado um novo coronavírus, o SARS-CoV-2. Este agente etiológico, causador da doença COVID-19, rapidamente se disseminou por todo o mundo, levando a Organização Mundial de Saúde (OMS) a decretar o estado de pandemia COVID-19, a 11 de março de 2020. A situação de emergência gerada, desafiou os sistemas de saúde e as autoridades competentes a nível mundial, exigindo a afetação excecional de recursos técnicos, financeiros e humanos, por forma a combater a crise de saúde pública instalada. O desenvolvimento de uma vacina eficaz contra a COVID-19, foi identificada como a melhor estratégia para suster a pandemia, levando à adoção de estratégias diferenciadas e da convergência de esforços por forma a acelerar o processo de desenvolvimento e introdução no mercado de vacinas contra a COVID-19. Neste estudo pretende-se analisar como decorreu o processo de introdução no mercado das vacinas COVID-19. Serão abordadas as especificidades regulamentares que foram adotadas de modo a permitir a célere aprovação e comercialização destas vacinas.
A new drug is subject to a rigorous research, development, evaluation, and approval process to ensure the quality, safety and efficacy of the drug and compliance with the requirements of the relevant regulatory authorities. Late in 2019, a new coronavirus, SARS-CoV-2, was identified. This etiological agent, causing the disease COVID-19, quickly spread throughout the world, leading the World Health Organization (WHO) to decree the state of pandemic COVID-19, on March 11, 2020.This emergency has challenged health systems and competent authorities worldwide, requiring the exceptional allocation of technical, financial, and human resources to combat the public health crisis. The development of an effective vaccine against COVID-19 was identified as the best strategy to halt the pandemic, leading to the adoption of differentiated strategies and the convergence of efforts to accelerate the process of development and market introduction of vaccines against COVID-19. This study aims to analyze how the market introduction process of the COVID-19 vaccines took place. The regulatory specificities that were adopted to allow the rapid approval and marketing of these vaccines will be addressed.