Tesi sul tema "Covid-19 – Vaccination"

During the Covid-19 vaccination in Croatia, there were inconsistencies and irregularities with the surplus vaccine and its recipients. Media coverage of the affair was extensive. The details were broadcasted in traditional media and social media. Like many other spheres of social life, the media system has progressed under the baton of technological and communication changes. The destabilisation of traditionally conducted communication required the adaptation and reshaping of all its actors. This study argues that we live in a hybrid media system, where traditional media and social media are in symbiosis (Chadwick, 2013) and are interconnected. The study aims to investigate what makes online content viral and discuss findings in a hybrid media context. The study conducts a content analysis, examining articles posted on media organisation web pages and their Facebook pages covering the vaccination affair. The variables in the analysis are based on the virality concept (taken from the field of marketing).

With emphasis on the arrival of Covid-19 vaccine in San Agustin Etla Mexico, the focus of this thesis is to investigate relations between ways of political organisation and vaccine uptake.   By having used a methodological framework of participant observation and semi-structured interviews from February to April 2021 this thesis illustrates responses that informants in the ages between 50-70 living in San Agustin Etla have to Covid-19 vaccine. I discuss aspects of a local vaccination culture, i.e., locally shaped responses to Covid-19 vaccine and reasons for vaccination and non-vaccination. Aspects I have found that may have affected a person’s response to Covid-19 vaccine are the spread/control of rumours, coercive measures, collective consciousness of risks, organisation of the household, social interaction, and earlier experience of vaccines. Based on the results of the investigation I argue that there is a correlation between the governance of “Usos y Costumbres” (practices and customs) in San Agustin Etla and vaccine uptake among people living there.

Магістерське дослідження присвячене цілісному аналізу проблемно-тематичних орієнтирів та особливостей висвітлення боротьби з COVID-19 в мас-медіа. У першому розділі розглянуто теоретико-методологічні основи дослідження, а саме проблему COVID-19 та історіографію її вивчення, а також методико-методологічні основи дослідження. У другому розділі розглянуто безпосередньо особливості висвітлення боротьби з COVID-19 в українських мас-медіа, а саме проблемно-тематичні орієнтири висвітлення боротьби з COVID-19 у перші три місяці та в останні три місяці пандемії, а також досліджено висвітлення питань, пов’язаних із COVID-19 як журналістську проблему. У ході дослідження простежено основні зміни у висвітленні питань, пов’язаних із COVID-19 у ЗМІ та виявлено, що головна зміна у висвітленні теми коронавірусу протягом останніх трьох місяців, порівняно із першими трьома місяцями полягає у тому, що додалася нова тема – вакцинація, яка супроводжує практично всю іншу інформацію, пов’язану з пандемією.

L'émergence de nouveaux pathogènes pose des défis importants aux autorités de santé publique. Dans le contexte de la pandémie de COVID-19, le SARS-COV-2 et les Variants of concern ont suivi un schéma similaire. : un nouveau virus apparait dans un pays, se propage à l'échelle mondiale et déclenche une augmentation rapide du nombre de cas dans le monde entier. Pour faire face à cette situation, il est essentiel de surveiller l'épidémie, de déchiffrer les données de surveillance incomplètes et incohérentes et de concevoir rapidement des interventions. Les modèles mathématiques peuvent aider à interpréter des données de surveillance hétérogènes et éclairer la conception des interventions. Dans cette thèse, nous avons abordé ces deux aspects. Tout d'abord, nous avons développé un cadre mathématique pour comprendre comment la surveillance et les facteurs impliqués dans de l'épidémie concourent à façonner les observations. Nous avons reconstruit rétrospectivement la propagation internationale de la variane Alpha à l'automne 2020 à partir de données de séquençage et de voyages aériens. Dans un second travail, nous nous sommes concentrés sur l'intervention. Nous avons proposé un modèle basé sur des agents pour quantifier l'impact épidémiologique d'une stratégie de vaccination réactive ciblant les lieux de travail et les écoles où des cas sont détectés. Nous avons testé l'efficacité de cette stratégie pour atténuer une augmentation générale du nombre de cas et pour limiter la propagation d'un nouveau variant
Emerging pathogens pose significant challenges to public health authorities. In the context of the COVID-19 pandemic, the SARS-COV-2 and the variants of concern followed a similar pattern. A new virus emerged in one country, spread globally, and then triggered a rapid surge in cases worldwide. To deal with this situation, it is critical to monitor the epidemic, decipher incomplete and incoherent data, and rapidly design interventions. Mathematical models can help interpret heterogeneous surveillance data and inform the design of interventions. In this thesis, we addressed both aspects. First, we developed a mathematical framework to understand how surveillance and epidemic drivers concur in shaping observations. We retrospectively reconstructed the international spread of the Alpha variant in the Fall of 2020 from sequencing and air travel data. In a second work, we focused on intervention. We proposed an agent-based model to quantify the epidemiological impact of a reactive vaccination strategy targeting workplaces and schools where cases are detected. We tested the effectiveness of this strategy to mitigate a general rise in cases and to limit the spread of a new variant

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

Inledning: Vaccinationstveksamhet är ett fenomen som är viktigt att studera eftersom bekämpningen mot covid-19 och andra sjukdomar är beroende av att befolkningen vaccinerar sig. Området Rinkeby-Tensta har tidigare haft låg vaccinationstäckning på grund av oro över biverkningar. Syftet är att ta reda på inställningen för vaccination mot covid-19 i Rinkeby-Tensta. Metod: En tvärsnittsstudie utfördes med bekvämlighetsurval. Resultat: Resultatet visar att 72 respondenter besvarade enkäten varav 78 procent av respondenterna svarade att de antingen inte vill eller inte vet om de vill vaccinera sig. Diskussion: Utbildningsnivå är inte associerat med vaccinationsviljan. Att senarelägga vaccinacceptansen uppfattas som en fördel. Bekymmer över vaccinets biverkningar är en faktor i vaccinationsbeslutet.
Introduction: Vaccine hesitancy is a phenomenon that is important to study when the fight against covid-19 and other diseases is dependent on the population being vaccinated. Rinkeby-Tensta previously had low vaccination coverage due to concerns about side effects. The aim is to measure the attitude toward vaccination against covid -19 in Rinkeby-Tensta Method: A cross-sectional study was performed with convenience sample. Results: Results show that 72 respondents answered the survey, of which 78 percent of the respondents answered that they either do not want or do not know if they want to get vaccinated. Discussion: Level of education is not associated with willingness to get vaccinated. To postpone vaccinations is perceived as a benefit. Concerns about the side effects of vaccine is a factor in the vaccination decision.

La pandémie de COVID-19, causée par le SRAS-CoV-2, a entrainé une morbidité et une mortalité importantes, mettant à rude épreuve les systèmes de santé mondiaux. Les vaccinations et les interventions non pharmaceutiques (INP) sont essentielles pour contrôler la propagation du virus. Avant les vaccins, les gouvernements s’appuyaient sur des INP dont l’impact épidémiologique et sociétal restait incertain, notamment sur plusieurs vagues pandémiques. Le déploiement des vaccins a augmenté l’immunité collective, mais l’émergence de variants préoccupants (VoCs) échappant à l’immunité et l’affaiblissement de l’immunité induite ont réduit l’immunité effective. La dynamique à long terme de ce déclin est mal comprise, surtout dans le contexte d’infections multiples et par divers VoCs. Les épidémies étant partiellement observées et leur dynamique non linéaire, les modèles mathématiques sont bien adaptés pour leur analyse. Dans ma thèse, j’ai appliqué ces modèles à diverses données COVID-19, depuis les données agrégées sur les infections et les hospitalisations jusqu’aux titres d’anticorps (Ac) chez les individus, pour quantifier l’efficacité des INP et vaccins, identifier les seuils de protection des Ac et caractériser la décroissance de l’immunité. Mon premier objectif était d’estimer l’efficacité des INP et des vaccins en France et d’explorer des scénarios contrefactuels des INP et des vaccins. Nous avons développé un modèle mécaniste ajusté aux données épidémiologiques françaises de mars 2020 à octobre 2021. Le modèle a montré une réduction significative de la transmission virale grâce aux INP, bien que leur efficacité ait diminué avec le temps. Les simulations ont montré que les vaccins avaient sauvé près de 160000 vies au cours de la période étudiée, mais qu’une mise en œuvre plus précoce ou un déploiement plus rapide aurait évité encore plus de décès. Pour comprendre la variabilité des estimations de l’efficacité des INP, nous avons évalué deux méthodologies pour mon deuxième objectif : les modèles mécanistes et une régression en deux étapes couramment utilisée, qui d’abord estime le nombre de reproduction ( Rt), puis le régresse sur les paramètres des INP. En utilisant des données simulées, les modèles mécanistes ont montré un biais minimal (0-5%) et une couverture d’intervalle de confiance (IC) élevée, tandis que les régressions en deux étapes ont montré des biais jusqu’à 20% et une couverture d’IC inferieure. Ce biais était dû à la déplétion des susceptibles et aux difficultés d’estimation de Rt, montrant que cette méthode nécessite prudence malgré sa rapidité. Les modèles épidémiologiques précis nécessitent des paramètres actualisés. Mon troisième objectif était donc 1) relier les niveaux d’Ac SARS-CoV-2 au risque de (ré)infection et 2) caractériser la décroissance des Ac. Grâce aux données d’Ac de plus de 220000 donneurs de sang canadiens entre avril 2020 et décembre 2023, nous avons constaté que les Ac anti-S et anti-N réduisaient le risque d’infection, avec un effet plus prononcé des anti-N à de faibles titres. J’ai estimé avec des modèles de décroissance biphasique que 51.3% (95% IC 40.6-66.1%) des individus tomberaient en dessous des niveaux détectables d’Ac anti-N dans les trois ans suivant une infection. La durée de détection des Ac augmentait après chaque infection. Cependant, les Ac chutaient en quelques mois en dessous des seuils requis pour une protection substantielle, même après plusieurs infections et vaccinations, indiquant la nécessité d’administrer des rappels réguliers pour maintenir la protection. Les analyses dans ma thèse soulignent l’importance des interventions rapides et du suivi continu de l’immunité pour mieux se préparer aux futures épidémies. De plus, j’ai démontré que les modèles mathématiques sont un outil puissant pour orienter la prise de décision en santé publique et les stratégies de prévention
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant morbidity and mortality, straining healthcare systems worldwide. Fundamental approaches for controlling viral spread and mitigating its impact are vaccinations and non-pharmaceutical interventions (NPIs). Before vaccines became available, governments relied on NPIs with largely unknown epidemiological and societal impacts. Despite numerous studies, the effectiveness of NPIs on COVID-19 dynamics remained uncertain, especially over multiple pandemic waves. With a gradual roll-out of vaccines, population immunity increased, but this increase in was counteracted by the emergence of immune-escaping variants of concern (VoCs) and waning of both infection- and vaccine-induced immunity. The long-term dynamics of this decline are currently not well characterized, particularly in the context of multiple infections and infections with different VoCs. Given the only partially observed nature of epidemics and their non-linear dynamics, mathematical models are uniquely suited for their analysis. In my thesis, I applied mathematical models to various COVID-19 data, from aggregated population-level data of infections and hospitalizations to antibody (Ab) titers in individuals, with the goal of quantifying the effectiveness of NPIs and vaccines, identifying protective Ab thresholds, and characterizing immunity waning dynamics. Specifically, my first objective was to estimate the effectiveness of NPIs and vaccines in France and explore counterfactual NPI and vaccine implementation scenarios. We developed a population-based mechanistic model, which we fit to epidemiological data in France from March 2020 to October 2021. The model showed a significant reduction in viral transmission by lockdowns, school closures, and curfews, though their effectiveness decreased over time. Simulations demonstrated that vaccines had saved nearly 160k lives over the study period, but an earlier implementation or a faster rollout could have prevented even more deaths. To understand why NPI effectiveness estimates vary across studies, we evaluated two methodologies in my second objective: mechanistic models and a commonly used two-step regression approach. The latter first estimates the reproductive number (Rt) and then regresses it against NPI parameters. Using simulated data of varying complexity, mechanistic models consistently showed minimal bias (0-5%) and high confidence interval (CI) coverage, whereas the two-step regressions had biases up to 20% and much lower CI coverage. The bias stemmed from the depletion of susceptibles and challenges in estimating Rt, indicating that caution is warranted with this method despite its simplicity and speed. Accurate epidemiological models require up-to-date parameters. My third objective was therefore two-fold: 1) to relate SARS-CoV-2 specific Ab levels to the risk of infection and 2) to characterize antibody waning. Using Ab data from over 220k Canadian blood donors between April 2020 and December 2023, we found that both anti-S and anti-N Abs reduced infection risk, with anti-N showing a stronger effect at lower titers. We used biphasic decay models to characterize waning dynamics and estimated that that 51.3% (95% CI 40.6-66.1%) of individuals would drop below detectable anti-N Ab levels within three years after a single infection. The duration of Ab detection increased after subsequent infections. However, antibodies waned within months below thresholds needed to attain substantial protection, even after multiple infections and vaccinations, indicating that continuous vaccine booster doses might be needed to sustain protection. The analyses I conducted in my PhD research highlight the importance of timely interventions and continuous monitoring of immunity to better prepare for future outbreaks. Moreover, I illustrated that mathematical models are a powerful tool to inform public health decision making and strategies

This study investigates if attitudes towards the pandemic recommendations made by the Public Health Agency of Sweden and if the estimation of their duration differ before and after a Covid-19 vaccination. The participants contributed to the study by filling out a questionnaire. A mass vaccination is a rare occurrence and few empirical studies have been conducted. A risk regarding a mass vaccination is that it can result in a premature relaxed mindset towards the recommendations, which can lead to an increased spread of the virus. To investigate this, we compared the responses from the participants who filled out the questionnaire before and after the Covid-19 vaccination. The results showed no differences in the attitudes towards the recommendations in the two groups, however tendencies of differences regarding the estimation of duration of the pandemic recommendations was discovered. Thus, we could not detect any large effects of a more relaxed mindset towards the recommendations, however we cannot exclude smaller effects. The results do not support that stricter recommendations should be introduced in order to counteract a more relaxed attitude.
Studien ämnar undersöka om inställningen till Folkhälsomyndighetens rekommendationer och uppskattningen av pandemirekommendationernas varaktighet skiljer sig åt före respektive efter vaccination mot covid-19. Deltagarna medverkade i studien genom att svara på ett frågeformulär.En massvaccinering är en sällsynt förekomst och få empiriska studier har genomförts. En risk vidgenomförandet av en massvaccinering är att den kan resultera i en för tidigt avslappnad inställning till rekommendationerna, vilket kan leda till en ökad smittspridning i samhället. Resultatet visade inte på några skillnader i inställningen till rekommendationerna mellan de två grupperna, dock fanns det tendenser till skillnader angående uppskattningen av pandemirekommendationernasvaraktighet. Således, utifrån studiens resultat, påvisades inte någon stor effekt av en avslappnad inställning efter en massvaccinering men det går inte att utesluta mindre effekter. Studiens resultatstyrker inte att strängare rekommendationer bör införas i en vaccinationsfas för att motverka en avslappnad inställning.

The first case of Covid-19 in Sweden was confirmed at the end of January 2020. At the time of conducting this study the society has begun vaccination against the virus. Although a majority of the population seem positive towards vaccination, the question remains which factors are influencing this attitude. The aim of this study is to create an understanding of how young adults in Sweden reason about Covid-19 and the vaccination thereof. The aim of this study is answered with the following question statements, how do young adults in Sweden reason about the risk of Covid-19 and the vaccination thereof and how do young adults in Sweden reason about the vaccination formed by their natural attitude and trust towards expert systems. Previous research shows that risk and trust towards expert systems are influential factors on individuals' inclination towards vaccines, regarding child vaccines or previous influenza vaccines. Antecedent quantitative studies show differences in vaccination attitudes between age categories and that young adults were most likely to have a negative attitude towards vaccines. This qualitative interview study, focusing on individuals in the age category of young adults, shows how risk and trust towards expert systems can influence their reasoning regarding Covid-19 and the vaccine against the virus, furthermore it shows how their natural attitudes can be affected by the pandemic. The result of this study shows that the studied young adults tend to see more risks with Covid-19 towards other people than themselves, which can be a contributing factor to the attitude towards vaccination of that age category. This study also shows that a high trust in expert systems can enable a positive reasoning regarding the vaccine and that the subjects of this study’s natural attitudes are changed by the pandemic.
Det första fallet av Covid-19 bekräftades i Sverige i slutet på januari 2020. Vid studiens genomförande har samhället påbörjat vaccineringen mot viruset. Även om majoriteten av befolkningen verkar positivt inställda till vaccinet återstår frågan om vilka faktorer som påverkar detta. Syftet med denna studie är att skapa en förståelse för hur unga vuxna i Sverige resonerar kring Covid-19 viruset och vaccinationen mot det. Syftet besvaras med följande frågeställningar, hur resonerar unga vuxna i Sverige kring risker med Covid-19 viruset och vaccinationen mot det och hur formas unga vuxna i Sveriges resonemang kring vaccinering av den naturliga inställningen och deras förhållningssätt till expertsystem. Tidigare forskning visar att risk och tillit till expertsystem kan vara påverkande faktorer på individers vaccinationsbenägenhet, åtminstone när det gäller barnvaccin eller tidigare influensavaccinationer. Tidigare kvantitativ forskning har även visat på skillnader i vaccinationsbenägenhet mellan åldersgrupper, där unga vuxna var mest troliga att vara negativt inställda. Denna kvalitativa intervjustudie med individer i åldersgruppen unga vuxna visar hur risk och tillit till expertsystem kan influera deras resonemang kring Covid-19 viruset och vaccineringen mot det samt hur deras naturliga inställning kan påverkas av pandemin. Resultatet av studien visar att respondenterna tenderar att se allvarligare på risker med Covid-19 gentemot andra än sig själva, något som kan vara en bidragande faktor till den åldersgruppens inställning till vaccinering. Studien visar även att en hög tillit till expertsystem möjliggör ett positivt resonemang kring vaccineringen och att den naturliga inställningen i pandemins samhälle är förändrad hos respondenterna.

Den nuvarande pandemin har begränsat mänskligheten och det digitala vaccinationspasset för covid-19 utlovar återgången till ett normalt liv. Studien syftar till att undersöka vilket handlingsutrymme ett vaccinationspass ger medborgare utifrån deras förväntningar och vaccinationspassets krav. Det digitala vaccinationspassets egenskaper och förutsättningar som digital artefakt undersöks i relation till affordance modellen. Forskningsstrategin för studien har varit en fallstudie av kvalitativ karaktär där datainsamlingen består av semistrukturerade intervjuer med medborgare i Sverige och en litteraturgenomgång som utgör den aktuella debatten i relaterade forskningen. Studien visar på hur medborgare uppfattar införandet av ett digitalt vaccinationspass för covid-19 och vill visa på rekommendationer i arbetet med tillgängliggörandet av det digitala vaccinationspasset för medborgarna. Studien grundar sig i att tillgängliggörandet av det digitala vaccinationspasset kommer att ske någonstans framöver och vi vill därför poängtera att resultatet inte kan fastslås utan kommer förändras beroende på förutsättningarna och tidsramen för undersökningen. Studien identifierar bristerna med förmedlingen av information samt myndigheternas globala ansvar vid införandet av ett digitalt vaccinationspass mot covid-19. För att hantera detta rekommenderar vi att en strategi bör utvecklas och även ett förtydligande av informationen gällande vaccinationspasset mot covid-19. Utifrån studien tolkas det att det digitala vaccinationspasset utformas för de rika och att covid-19 har påskyndat digitalisering av samhället. Vi anser att alla bör ha tillgång till vaccin och tillgång till digital teknik innan det digitala vaccinationspasset mot covid-19 införs.
The current pandemic has limited humanity and the digital vaccination passport for covid-19 promises the return to a normal life. The study aims to investigate what room for maneuver a vaccination passport gives citizens based on their expectations and the requirements of the vaccination passport. The properties and conditions of the digital vaccination passport as a digital artifact are examined in relation to the affordance model. The research strategy for the study has been a case study of a qualitative nature where the data collection consists of semi-structured interviews with citizens in Sweden and a literature review that constitutes the current debate in related research. The study shows how citizens perceive the introduction of a digital vaccination passport for covid-19 and wants to show recommendations in the work of making the digital vaccination passport available to citizens. The study is based on the fact that the digital vaccination passport will be made available somewhere in the future and we therefore want to point out that the result can not be determined but will change depending on the conditions and time frame for the examination. The study identifies the shortcomings with the dissemination of information as well as the authorities' global responsibility in introducing a digital vaccination passport against covid-19. To deal with this, we recommend that a strategy should be developed and also a clarification of the information regarding the vaccination passport against covid-19. Based on the study, it is interpreted that the digital vaccination passport is designed for the rich and that covid-19 has accelerated digitization of society. We believe that everyone should have access to vaccines and access to digital technology before the digital vaccination passport against covid-19 is introduced.

La pandémie de COVID-19 causée par le virus SARS-CoV-2 a nécessité une compréhension approfondie de la réponse immunitaire afin de développer des stratégies de prévention et de traitement efficaces. Rapidement, la communauté scientifique a démontré que l'immunité humorale induite par l'infection ou la vaccination était capable de générer des anticorps protecteurs neutralisants contre l'infection et la sévérité de la maladie chez l'homme. Cependant, il a été observé que la protection conférée par ces anticorps diminue rapidement dans le temps, en raison de l'échappement des variants du SARS-CoV-2 aux capacités neutralisantes des anticorps, ainsi qu' à la diminution de leur concentration au fil du temps. Il a également été démontré que la vaccination et l'infection peuvent induire une immunité cellulaire médiée par les lymphocytes T. Cette immunité semble persistée plus longtemps que l'immunité humorale et serait capable de reconnaître plus efficacement les différents variants du SARS-CoV-2. Des résultats expérimentaux chez l'homme et dans des modèles animaux ont suggéré que ce type d'immunité pourrait également jouer un rôle protecteur complémentaire à l'immunité humorale. Cependant, les caractéristiques moléculaires de cette immunité cellulaire protectrice ne sont pas encore bien définies. Cette thèse s'est donc concentrée sur l'impact de la polarité et de la spécificité des lymphocytes T sur la protection contre l'infection par le SARS-CoV-2. Premièrement, nous avons caractérisé de manière extensive la polarité et la spécificité des réponses immunitaires cellulaires spontanées ou induites par l'infection naturelle. Nos résultats ont révélé que la polarité Th1 était associée à une protection contre l'infection. De plus, nous avons identifié les réactivités dirigées contre la zone RBD (Receptor Binding Domain) comme étant les plus importantes dans ces réponses protectrices. Ces résultats ont posé les bases pour le développement d'un test cellulaire permettant de suivre à grande échelle ces réponses immunitaires protectrices. Deuxièmement, nous avons examiné l'effet de la vaccination sur la réponse immunitaire cellulaire. Nous avons confirmé que le nombre de vaccinations était en effet capable de renforcer l'immunité cellulaire dirigée contre la zone RBD. Nous avons identifié les patients atteints de maladies hématologiques malignes comme une population vulnérable chez laquelle la réponse immunitaire cellulaire était altérée malgré la vaccination. Dans cette population, les réponses immunitaires dirigées contre la zone RBD étaient très importantes pour la protection contre l'infection. Nous avons égalexploré l'évolution de la réponse immunitaire au fil du temps et en fonction du nombre de doses de vaccin administrées. Nos analyses ont révélé une diminution des concentrations de l'interféron gamma (IFN-y) avec le temps, jusqu'à atteindre une stabilisation durable, confirmant la longévité des réponses cellulaires. Nous avons également mis en évidence l'échappement du variant Omicron à la protection conférée par la sécrétion d'IFN-y anti-RBD. Cette constatation a souligné le besoin urgent de nouveaux biomarqueurs pour évaluer l'efficacité de la vaccination contre le variant Omicron. Dans ce contexte, nous avons identifié la chimiokine CXCL10 comme un potentiel marqueur d'efficacité vaccinale. En conclusion, cette thèse a contribué à une meilleure compréhension de la réponse immunitaire induite par le SARS-CoV-2 et les vaccins. Les résultats obtenus offrent des outils pour orienter les politiques vaccinales et le développement de nouveaux vaccins. De plus, l'identification de nouveaux biomarqueurs et l'exploration de la polarité et de la spécificité des lymphocytes T ouvrent des perspectives prometteuses pour le développement de vaccins personnalisés. Ces avancées sont cruciales dans la lutte contre la pandémie de COVID-19 et pour se préparer aux futures épidémies virales
The 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

This work examines whether a debiasing intervention using a debiasing tool would prove effective in tackling confirmation bias regarding Covid-19 vaccination. The experiment was conducted through a questionnaire which included measures of attitudes, different texts for the debiasing intervention and the control group, as well as two measures of the effectiveness of the intervention. The results showed that the intervention was ineffective and there was no observed change in the level of confirmation bias among the participants.

Dissertação de Mestrado apresentada no ISPA – Instituto Universitário para obtenção de grau de Mestre na especialidade de Psicologia Clínica
Objetivo: Estudar se em Portugal a vivência da atual pandemia COVID-19, as dúvidas resultantes dessa vivência e do aparecimento das novas vacinas COVID-19, conduziram a um decréscimo na intenção dos indivíduos se vacinarem; avaliar qual o efeito de variáveis como a Literacia em Saúde, Perceção da Doença (COVID-19) e Perceção do Risco nas intenções de vacinação contra a COVID-19 segundo o modelo de correlação de Pearson e pelo modelo de mediação tendo como variáveis mediadoras a Perceção da Doença e a Perceção do Risco. Método: Foram incluídos na análise 454 participantes adultos residentes em Portugal. Para recolha de dados, os instrumentos utilizados foram o Newest Vital Sign (NVS) para medir a Literacia em Saúde, The Brief IPQ, um questionário para medir a Perceção do Risco percebida e comparada e um outro para medir Intenção de Vacinação com o último item dedicado às dúvidas sobre a vacinação (COVID-19). Resultados: Observou-se que não existe correlação entre as variáveis Literacia em Saúde, Perceção da Doença e Perceção do Risco e a Intenção de Vacinação. Não se confirmou o modelo de Mediação com as variáveis mediadoras Perceção da Doença e Perceção do Risco. Os diferentes tipos de dúvidas quanto à vacinação (COVID-19) tiveram um impacto negativo na Intenção de Vacinação. Conclusões: As preocupações com a segurança da vacina devem ser abordadas antes e durante a implementação do programa de vacinação
Objective: To study if in Portugal, the experience of the pandemic COVID-19, the doubts resulting from it and the appearance of new vaccines for COVID-19, lead to a decrease in people’s intention to be vaccinated; to evaluate the effect of variables such as Health Literacy, Illness Perception (Covid-19) and Risk Perception on the intention of vaccination, through Pearson correlation model and the mediation model, which have as mediating variables the Illness Perception and the Risk Perception. Methods: There were included in the analysis 454 adult participants living in Portugal. For the data collection, the instruments used were the Newest Vital Sign (NVS), to measure the Health Literacy, The Brief IPQ, a questionnaire to measure the perceived and compared risk perception and another one for the vaccination intention as the last item was dedicated to doubts regarding the vaccine (COVID-19). Results: It was observed that there isn't any correlation between the variables Health Literacy, Illness Perception and Risk Perception and the Intention of Vaccination. It also wasn't confirmed the mediation model with the Illness Perception and the Risk Perception. The different types of doubts regarding the vaccine (COVID-19) had a negative impact in the intention to be vaccinated. Conclusions: The safety issues regarding the vaccine must be addressed continuously, before and after the implementation of the vaccine program.
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The current dissertation was developed during the outbreak of the COVID-19 pandemic in Italy. The central theme of the present work focuses on the belief that, during this time of extreme difficulty for the world's population, COVID-19 pandemic can be brought under control mainly by massive and rapid behaviour change. One way to achieve this goal is to systematically monitor and understand how different individuals perceive risk and adhere to protective behaviours. The main aim of the present work is to understand whether there exist cognitive, social and psychological predictors of protective behaviours against COVID- 19. In particular, the dissertation takes into consideration three main topics: risk perception, social distancing and vaccine intention in the Italian population. It comprises a detailed letterature review on these topics and three experimental works addressing each aspect. The general suggestion of the present work is that behavioral insights concerning the pandemic are of most importance for governments and the world's population for developing strategies to deal with COVID-19 and other possible pandemics in the future.

Immunomodulation is a process by which the immune response of the host is either enhanced or suppressed due to various factors which either protects or makes the host more susceptible to particular diseases. Immunomodulators are a broad class of drugs that are used either to suppress (immunosuppressants) or enhance (immunostimulants) immune responses. These have been used to combat against the dysregulated immune system, observed during tissue/organ transplantation and disorders such as rheumatoid arthritis, ulcerative colitis and cancer. Plant-based immunomodulators such as capsaicin, curcumin and resveratrol are extensively used as immunomodulators and anti-inflammatory drugs. Sesquiterpene lactones are a major class of plant-based immunomodulators that are derivatives of sesquiterpenoids and are obtained from Asteraceae. These molecules are known for its anti-inflammatory and anti-tumor effects. The objective of my first study was to understand the roles of 7-hydroxy frullanolide (7HF) on different immune cells and to decipher the underlying mechanisms of action. Primary CD4+ T cells were isolated from lymph nodes of C57BL/6 mice, followed by treatment with different doses of 7HF and in-vitro activation with plate bound (pb) αCD3 and soluble αCD28. 7HF in a dose dependent manner caused a reduction in IL2 production and inhibition of upregulation of CD69, an early activation marker in CD4+ T cells. Subsequently, it was also observed that 7HF abrogated the increase in cell size and cellular proliferation with T cell activation. Ca2+ -dependent signaling pathways are an indispensable part of CD4+ T cell activation and overall T cell responses; hence it was important to understand whether 7HF had any effects on Ca2+ levels. Surprisingly, 7HF increased intracellular Ca2+ levels, more than optimal levels, during CD4+ T cell activation at early timepoints. We functionally confirmed this observation using a specific intracellular Ca2+ chelator, BAPTA-AM which rescued cellular proliferation with 7HF treatment during CD4+ T cell activation. To understand how 7HF caused a significant increase in intracelullar Ca2+ amounts, we performed Ca2+ channel inhibitor studies to understand whether 7HF behaved as a Ca2+ channel agonist in CD4+ T cells. Additionally, 7HF also caused a significant increase in extracellular lactate amounts which was functionally confirmed using 2-Deoxy D-glucose (2DG) experiments suggesting that 7HF was working on multiple fronts to hinder T cell responses. Subsequently, we tried to understand whether there was a link between increased Ca2+ levels and lactate levels during CD4+ T cell activation. Finally, to understand whether there is a link between Ca2+ and lactate, experiments were done using BAPTA-AM that confirmed Ca2+ levels did regulate lactate levels during CD4+ T cell activation. Next, we tried to understand the effect 7HF had on other immune cells. Although 7HF had no effect on lipopolysaccharide (LPS) stimulated splenocytes which primarily activates B cells, 7HF did inhibit activation of LPS treated adherent peritoneal macrophages with respect to nitrite and IL6 amounts in a dose dependent manner. Furthermore, 7HF inhibited peritoneal macrophage activation via a Ca2+ dependent mechanism. Ca2+ channel inhibitor studies also suggested that 7HF was behaving as a Ca2+ channel agonist in peritoneal macrophages, similar to CD4+ T cells. However, 7HF had no effect on lactate levels in peritoneal macrophages as compared to CD4+ T cells. Lastly, we wanted to identify the molecular mechanisms by which 7HF was acting as a Ca2+ agonist. Thus, we performed autodocking experiments using the autodock modelling simulation software and standardized the binding of 7HF to Ca2+ channels. We initially obtained the crystal structure of the Ca2+ channel proteins, IP3R and TRPV1 and tried to dock the 3D structure of the ligands into the respective pockets of the protein molecules. We observed that 7HF was binding to both TRPV1 and IP3R Ca2+ channels with a significant binding energy when compared to the positive controls. Hence it is likely that 7HF behaved as a Ca2+ channel agonist to greatly increase Ca2+ amounts that inhibited both T cell and macrophage responses. To understand the physiological relevance of 7HF, we performed in-vivo experiments with 7HF using the Dextran sulfate sodium (DSS) induced colitis model of mice which is an animal model of autoimmune Inflammatory Bowel Disease. We used the golden standard of estimating the severity of colitis by measuring the colon length. DSS, as reported, caused a severe shortening of colon length which was rescued by 7HF in a dose dependent manner. The extent of colon damage as observed due to severe damage in the crypts and extensive immune cell infiltration by DSS was significantly reduced by 7HF. Also, 7HF rescued the loss in thymocyte and mesenteric lymph node (MLN) cell numbers due to DSS treatment. Finally, 7HF significantly reduced the amounts of proinflammatory cytokines, IFNγ and IL6 in the sera. Overall, this study clearly demonstrates the in-vivo effects of 7HF as an anti-inflammatory molecule. Both in-vitro and in-vivo studies together strengthen the observation that 7HF may have potential therapeutic applications to treat different autoimmune disorders. My next study was performed during the Covid-19 pandemic. An epidemiological study was performed during the months of April-June 2020 to understand the effects of pathogen exposure and vaccination coverage on Covid-19-induced mortality. Covid-19 deaths display a high heterogeneity across different countries and the extent of infection in a particular population might be dependent on multiple factors such as age, sex, temperature, humidity etc. This led us to perform correlation studies with 36 (out of 215) countries having more than 1000 Covid-19 deaths as of 24th June 2020. The major observations of this study are: measles, HBV and polio vaccination coverage had no correlation with Covid-19 incidences and deaths. Subsequently, flu incidences had no correlation with respect to Covid-19 incidences and deaths. However, flu deaths showed a significant negative correlation with Covid-19 mortality rate and Covid-19 deaths/million. Additionally, flu vaccination had a significant positive correlation with Covid-19 incidences, Covid-19 deaths, mortality rate and Covid-19 deaths/million. Next, Tuberculosis (TB) only negatively correlated with Covid-19 mortality rate and Covid-19 deaths/million. This trend was also holding for TB deaths. Similarly, Bacillus Calmette Guerin (BCG) coverage had a significant negative correlation with Covid-19 deaths, mortality rate and Covid-19 deaths/million suggesting its protective role. Interestingly, countries which have flu, but no BCG, vaccination show highest number of Covid-19 deaths. Countries that have high flu and BCG vaccinations demonstrate more immunomodulatory effects in determining the fate of a particular disease and its effects on the host.

Introdução: A resposta à pandemia provocada pelo vírus SARS-CoV-2 e as vacinas desenvolvidas têm encontrado obstáculos criados pela disseminação de notícias falsas e conspirações propagadas pelo movimento antivacinação nas redes sociais. Desta forma, a hesitação vacinal poderá ter contornos nunca antes vistos, em Portugal, até ao momento. Métodos: Este estudo analisa as publicações, comentários e membros do grupo do Facebook “Anti-VAX Portugal” desde 10 de abril a 10 de outubro de 2020, no decorrer da pandemia. Foi também aplicado um inquérito por questionário online, onde se procura compreender a influência que os conteúdos antivacinais tiveram sobre os utilizadores das redes sociais no processo de decisão de vacinação contra a COVID-19. Resultados: A partir da análise deste grupo, compreendendo 347 membros e com motivações distintas, foram identificadas 440 publicações, das quais 48% são teorias da conspiração. A partilha de publicações contra a vacina para a COVID-19 iniciou-se ainda antes da existência efetiva da vacina. No inquérito online aferimos que a influência dos conteúdos antivacinação na rede social Facebook sobre indivíduos indecisos é quatro vezes superior do que se estes não se deparassem com tais conteúdos. No caso daqueles que se mostravam decididos a não se vacinar contra o vírus SARS-CoV-2, mais de metade foram expostos a conteúdos antivacinação. Conclusão: Este movimento é altamente capacitado para influenciar a opinião de outros através de campanhas antivacinação, realizadas antes da criação da vacina para a COVID-19, e as redes sociais são o veículo ideal para a disseminação e a organização de ações fora do espaço digital.
Background: The pandemic by SARS-CoV-2 virus and the vaccines developed will face obstacles created by the dissemination of fake news and conspiracies propagated by the anti-vaccination movement on social media. Thus, the vaccine hesitation will have contours never seen before, in Portugal. Methods: This study analyzes the posts, comments, and members of the Facebook group “Anti-VAX Portugal” from April 10th to October 10th, during the pandemic. As well as the development of an online questionnaire survey where we understand the influence that anti-vaccination content has on social media users to take the COVID-19 vaccine. Results: The analysis of 347 members, with different motivations, culminates in 440 publications where 48% are conspiracy theories. Vaccine sharing for COVID-19 started long before there was one. In the online survey, we verified that the influence of anti-vaccination content on social media, on hesitant individuals, is four times higher than if they had not come across such content. Also, for those who have already decided that they will not be vaccinated against the SARS-CoV-2 virus, more than half were exposed to the contents of the anti-vaccination movement. Conclusion: This movement is highly capable of influencing the opinion of others through anti-vaccination campaigns, carried out before the creation of the vaccine for COVID-19 and social media is the ideal vehicle for the dissemination and organization of actions outside the digital space.