Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.Fil: Sekine, Takuya. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Perez Potti, André. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Rivera Ballesteros, Olga. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Strålin, Kristoffer. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Gorin, Jean Baptiste. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Olsson, Annika. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Llewellyn Lacey, Sian. University Hospital of Wales; Reino UnidoFil: Kamal, Habiba. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Bogdanovic, Gordana. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Muschiol, Sandra. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Wullimann, David J.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Kammann, Tobias. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Emgård, Johanna. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Parrot, Tiphaine. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Folkesson, Elin. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Rooyackers, Olav. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Karolinska University Hospital; SueciaFil: Eriksson, Lars I.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Henter, Jan Inge. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sönnerborg, Anders. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Allander, Tobias. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Albert, Jan. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Klingstrom, Jonas. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Gredmark Russ, Sara. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Björkström, Niklas K.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sandberg, Johan K.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Price, David A.. Cardiff University School of Medicine; Reino UnidoFil: Ljunggren, Hans Gustaf. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Aleman, Soo. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Buggert, Marcus. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

Proteomics of the human meniscus in health and osteoarthritis

Introduction: Osteoarthritis (OA) is one of the most common causes of knee pain, and the most common form ofarthritis. It causes pain and disability, and there is currently no cure. Recent research in knee OA highlights therole of the meniscus in OA pathology. In this thesis, the overall aim was to study the proteome and microstructureof the human meniscus, both in healthy subjects and OA patients, in order to increase our knowledge about thehuman meniscus and the processes that occur during degeneration and OA.Design: In the first part of this thesis, posterior horns of medial and lateral menisci from deceased donors and OApatients were analysed with histology and micro-computed tomography (μCT), in order to compare themicrostructure of healthy and OA menisci (paper I). In the second, and major part of this thesis, human menisciwere analysed with mass spectrometry (MS)-based proteomics. First, meniscus body samples and articularcartilage samples from deceased donors were compared using two different MS-based methods – dataindependentacquisition (DIA) and data-dependent acquisition (DDA) (paper II). Next, three zones (peripheral,middle and inner zone) of the body of the medial meniscus from deceased donors were compared using DIA(paper III). Lastly, meniscal plugs from the same meniscal posterior horns that had been used in paper I, wereanalysed with DIA.Results: In paper I, we found that higher histopathological scores were associated with more degeneration, andthat medial menisci from OA patients had the highest degree of degeneration. We also observed that the degreeof degeneration varied between the different sections of the meniscus. In paper II, we showed that the majority ofthe proteins were similar between articular cartilage and meniscus, but that there were nonetheless someproteomic differences. Furthermore, we found that DIA identified more differentially expressed proteins, with lessmissing values. In paper III, we observed that many proteins were common to all zones of the meniscus, and thatthe majority of meniscal proteins were associated with ECM organisation. The largest zonal differences werebetween the peripheral and inner zones. In paper IV, where we compared menisci from OA patients and deceaseddonors, we showed that the largest differences could be seen between the medial menisci from the two groups,and that there was an increase of proteoglycans and proteins such as MMP3 and TIMP1.Conclusions: Due to the many advantages of DIA, we considered it superior to DDA and used it in subsequentMS analyses. Although articular cartilage and meniscus had similar proteomic compositions, we detected severaldifferences by MS. We also detected large differences between the peripheral and inner zones of the healthymeniscus body, probably related to the higher degree of cellularity and vascularisation in the peripheral zone. Onthe other hand, the middle and inner zones of the meniscus contained more extracellular proteins and thereforeappeared to be more similar to articular cartilage. Comparison of healthy and OA menisci revealed increaseddegeneration of the OA menisci, with more disorganised collagen networks and the presence of cysts andcalcifications. The OA menisci also had an increase of proteins such as MMP3 and TIMP1, which suggestssimultaneous activation of both catabolic and anabolic processes. The increased degeneration in OA meniscisuggests a strong association between OA and meniscal degeneration

Transactional and transformative leadership : A quantitative study on the impact of leadership style on employees' work motivation

Ständig forskning pågår kring begreppet ledarskap i relation med andra viktiga delar som inkluderas i ledarskapet. Tidigare studier har undersökt ledarskapets påverkan på medarbetarnas motivation men resultaten är spretiga och trots omfattande studier tycks forskare inte vara helt överens. Forskningen kring ledarskap har gått från att främst handla om ledaren till att även inkludera följderna av ledarskapet. Det är även grunden för denna studie vars syfte är att förklara hur den transformativa och transaktionella ledarskapsstilen påverkar medarbetarnas motivation i arbetet samt beskriva på vilka sätt medarbetare inom rekryterings- och bemanningsbranschen i Sverige motiveras olika beroende på könstillhörighet. Studien är uppbyggd på en kvantitativ metod där hypoteser är utformade för att besvara studiens forskningsfrågor. Hypoteserna och forskningsfrågorna i studien undersöker ledarskapsstil och motivation indelat i inre och yttre motivation. Enkätundersökningen är utformad i Webbankäter.com och de påståenden som återfinns i enkäten är inspirerade av mätinstrumentet Multifactor Leadership Questionnaire (MLQ). Utöver det är påståendena också formulerade utifrån dimensionerna inom det transformativa och transaktionella ledarskapet samt de ledarskapsbeteenden som återfinns inom respektive dimension. Studiens resultat visar att ledarskapsbeteenden inom det transformativa ledarskapet har en signifikant positiv påverkan på både män och kvinnors motivation, dock motiveras de av olika dimensioner och beteenden. Resultaten gällande det transaktionella ledarskapet visar att det endast är två dimensioner inom ledarskapet som har en signifikant positiv påverkan på män och kvinnors motivation.Constant research is being conducted on leadership in relation to other important elements that are included in leadership. Previous studies have investigated the impact of leadership on employee motivation but the results are scattered and despite extensive studies, researchers don't seem to be in a complete agreement. Research has gone from primarily focusing on the leader to also including the consequences of leadership. That is also the purpose with this study, that aims to explain how the transformative and transactional leadership style affects employees motivation and describe in what ways employees in the recruitment- and staffing industry in Sweden are motivated differently depending on gender. The study is based on a quantitative method and hypotheses are designed to answer the study’s research questions. The hypotheses and research questions in the study investigate leadership style and motivation divided into intrinsic and extrinsic motivation. The survey is designed in Webbenkäter.com and the statements found in the survey are inspired by the Multifactor Leadership Questionnaire (MLQ). In addition to that, the statements are also formulated based on the dimensions within transformative and transactional leadership and the leadership behaviors found within each dimension. The results of the study shows that the behaviors within the transformative leadership has a significant positive impact on both men and women’s motivation, although they are motivated by different dimensions and behaviors within the transformative leadership. The results regarding transactional leadership shows that only two of the three dimensions has a significant positive impact on men and women’s motivation

Tidig identifiering av patienter med sepsis i den prehospitala vården : En systematisk integrativ litteraturstudie

Sepsis är ett globalt förekommande hälsoproblem, med snabbt förlopp och hög dödlighet, som kan drabba alla individer och anses vara en global hälsokris. Patienter som överlever riskerar långvariga konsekvenser, tidig identifiering har visat sig minska lidande och dödlighet och är därför av största vikt. Att identifiera sepsis är komplext då det innefattar flera symtom och tecken. Syftet med denna integrativa systematiska litteraturstudie var att beskriva faktorer för, och prehospital vårdpersonals erfarenheter av, tidig identifiering av sepsis i en akut prehospital vårdkontext. Metoden valdes enligt Whittemore & Knafl (2005) som är gjord för systematisk integrativ litteraturstudie. Resultatet baserades på 16 vetenskapliga artiklar med kvantitativ, kvalitativ och mixad metod. Patienter som transporterades och vårdades av ambulanssjukvården var svårare sjuka än de som själv tog sig till sjukhus, hade högre risk att avlida i sepsis, patienterna var äldre, samsjukliga och hade påverkat medvetande. Vissa symtom och tecken var mer förekommande, men variationen hos individen gör identifieringen komplex. Bland faktorerna för att lyckas med tidig identifiering av sepsis fanns det förutsättningar som omgärdade den prehospitala vårdpersonalens bedömning. Kunskap och utbildning om sepsis är en del i att tidigt kunna identifiera sepsis. Prehospital vårdpersonal som hade högre utbildning var bättre på att identifiera sepsis. Identifiering av sepsis är komplext och utgörs av både demografi, fysiologiska fynd, vårdpersonals samlade förutsättningar och system för att bedöma patienter. Det är inte tillräckligt att enbart beakta en faktor för att lyckas med tidig identifiering av sepsis, ambulanssjuksköterskan behöver beakta en sammanvägning och medvetenhet om de olika faktorer som behövs för att på bästa sätt lyckas.

Compared to other elderly, I have a dream life : A qualitative study about quality of life among elderly persons in need of care

Syftet med denna studie var att undersöka faktorer av betydelse för en upplevd livskvalitet bland äldre personer i behov av omsorg. Studien har en hermeneutisk ansats. Data samlades in via enskilda djupintervjuer med fyra äldre personer boende på ett trygghetsboende i en värmländsk kommun. Hälsa, aktivitet och intressen, anhöriga och vänner, boende samt acceptans av sitt eget liv och åldrande var faktorer av betydelse.   Hälsan beskrevs utifrån två olika dimensioner, som faktiskt hälsostatus och subjektivt upplevd hälsa. Att vara delaktig i aktivitet och utföra sina intressen var viktigt för de äldre. Resultaten visade att de äldres tidigare intressen var viktiga att bevara, även om det var i en annan omfattning – radio och tv gav dem möjlighet till fortsatt bejakande av intressen. Respondenterna upplevde att de var tätt sammanflätade med sina anhöriga och det var av stor betydelse för dem att vara delaktiga i deras liv genom att exempelvis få telefonsamtal samt besök. Boendeformen tillskrevs stor betydelse utifrån trygghet och möjlighet till avslappning. De äldre hade inte längre ansvar för praktiska göromål, som exempelvis snöskottning och andra hemsysslor. Acceptans av sitt eget liv och åldrande hade stor vikt för upplevelsen av livskvalitet. De äldre personerna beskrev att de kunde acceptera och hantera negativa händelser i nuet om livet i sin helhet sammanfattades av dem själva som positivt. Att lämna över personligt värdefulla ting till sina barn beskrevs av respondenterna som något mycket viktigt.   Resultaten tolkades utifrån gerotranscendensteorin och KASAM för att nå en bredare förståelse för de äldres upplevelse av livskvalitetThe purpose of this study was to investigate determinants of a perceived quality of life among older persons in need of care. The study has a hermeneutical approach. Data were collected through individual interviews with four older people living at a sheltered housing in a municipality in Värmland. Health, activity and interests, relatives and friends, accommodation and acceptance of one's own life and aging were relevant factors.   Health was described in two different dimensions, which are actually health status and subjective perceived health. To participate in the activity and performance of their interests was important for the elderly. Results showed that the elderly former interests were important to preserve, even if it was on a different scale - radio and television gave them the opportunity for continued affirmation of interests. Respondents felt that they were interwoven with his family and it was important for them to be involved in their lives, for example by getting phone calls and visits. Housing form was ascribed great importance on the basis of security and opportunity for relaxation. The elderly no longer had responsibility for practical tasks, such as snow shoveling and other chores. Acceptance of one's own life and aging had great importance for the perception of quality of life. The elderly subjects stated that they could accept and deal with negative events in the present moment of life as a whole was summed up by themselves as well. To hand over personal valuable things to their children was described by respondents as something very important.   The results were interpreted on the basis gerotranscendens theory and SOC to reach a broader understanding of older people's experience of lif

Transactional and transformative leadership : A quantitative study on the impact of leadership style on employees' work motivation

Ständig forskning pågår kring begreppet ledarskap i relation med andra viktiga delar som inkluderas i ledarskapet. Tidigare studier har undersökt ledarskapets påverkan på medarbetarnas motivation men resultaten är spretiga och trots omfattande studier tycks forskare inte vara helt överens. Forskningen kring ledarskap har gått från att främst handla om ledaren till att även inkludera följderna av ledarskapet. Det är även grunden för denna studie vars syfte är att förklara hur den transformativa och transaktionella ledarskapsstilen påverkar medarbetarnas motivation i arbetet samt beskriva på vilka sätt medarbetare inom rekryterings- och bemanningsbranschen i Sverige motiveras olika beroende på könstillhörighet. Studien är uppbyggd på en kvantitativ metod där hypoteser är utformade för att besvara studiens forskningsfrågor. Hypoteserna och forskningsfrågorna i studien undersöker ledarskapsstil och motivation indelat i inre och yttre motivation. Enkätundersökningen är utformad i Webbankäter.com och de påståenden som återfinns i enkäten är inspirerade av mätinstrumentet Multifactor Leadership Questionnaire (MLQ). Utöver det är påståendena också formulerade utifrån dimensionerna inom det transformativa och transaktionella ledarskapet samt de ledarskapsbeteenden som återfinns inom respektive dimension. Studiens resultat visar att ledarskapsbeteenden inom det transformativa ledarskapet har en signifikant positiv påverkan på både män och kvinnors motivation, dock motiveras de av olika dimensioner och beteenden. Resultaten gällande det transaktionella ledarskapet visar att det endast är två dimensioner inom ledarskapet som har en signifikant positiv påverkan på män och kvinnors motivation.Constant research is being conducted on leadership in relation to other important elements that are included in leadership. Previous studies have investigated the impact of leadership on employee motivation but the results are scattered and despite extensive studies, researchers don't seem to be in a complete agreement. Research has gone from primarily focusing on the leader to also including the consequences of leadership. That is also the purpose with this study, that aims to explain how the transformative and transactional leadership style affects employees motivation and describe in what ways employees in the recruitment- and staffing industry in Sweden are motivated differently depending on gender. The study is based on a quantitative method and hypotheses are designed to answer the study’s research questions. The hypotheses and research questions in the study investigate leadership style and motivation divided into intrinsic and extrinsic motivation. The survey is designed in Webbenkäter.com and the statements found in the survey are inspired by the Multifactor Leadership Questionnaire (MLQ). In addition to that, the statements are also formulated based on the dimensions within transformative and transactional leadership and the leadership behaviors found within each dimension. The results of the study shows that the behaviors within the transformative leadership has a significant positive impact on both men and women’s motivation, although they are motivated by different dimensions and behaviors within the transformative leadership. The results regarding transactional leadership shows that only two of the three dimensions has a significant positive impact on men and women’s motivation

Navigating in Swedish Clothing Companies' Supply Chain : A study on how big and micro Swedish clothing companies contribute to transparency in the supply chain

Problem: The Swedish clothing industry is unsustainable in many ways. In recent years, the demand from consumers for companies to be sustainable has increased. Additionally, the demand for transparency has increased as well. However, due to a lack of strong regulations regarding transparency, it is hard for stakeholders to ensure that clothing companies are following their own statements.   Purpose: This study aims to identify how different companies act to gain or maintain transparency throughout their supply chains, depending on the size of their company.   Method: The research was conducted following the paradigm of interpretivism and an inductive approach to research, where six qualitative semi-structured interviews were conducted. The interviewees represented six Swedish clothing companies. The empirical findings were analyzed and then compared with previous research in the field.   Findings: The result of this study show that supply chain transparency is strongly related to having strong, trustworthy relationships with all stakeholders in the supply chain. Trust generates control and insights into operations. Transparency is also strongly related to traceability. The level of trust and transparency in a company's supply chain can be dependent on financial means and how long they have been in business and therefore differ between companies of different sizes. Furthermore, the study highlights the need for strong legislative action to improve transparent actions.

Navigating in Swedish Clothing Companies' Supply Chain : A study on how big and micro Swedish clothing companies contribute to transparency in the supply chain

Problem: The Swedish clothing industry is unsustainable in many ways. In recent years, the demand from consumers for companies to be sustainable has increased. Additionally, the demand for transparency has increased as well. However, due to a lack of strong regulations regarding transparency, it is hard for stakeholders to ensure that clothing companies are following their own statements.   Purpose: This study aims to identify how different companies act to gain or maintain transparency throughout their supply chains, depending on the size of their company.   Method: The research was conducted following the paradigm of interpretivism and an inductive approach to research, where six qualitative semi-structured interviews were conducted. The interviewees represented six Swedish clothing companies. The empirical findings were analyzed and then compared with previous research in the field.   Findings: The result of this study show that supply chain transparency is strongly related to having strong, trustworthy relationships with all stakeholders in the supply chain. Trust generates control and insights into operations. Transparency is also strongly related to traceability. The level of trust and transparency in a company's supply chain can be dependent on financial means and how long they have been in business and therefore differ between companies of different sizes. Furthermore, the study highlights the need for strong legislative action to improve transparent actions.