Pat. mit Multipler Sklerose haben ein erhöhtes Risiko, einen schweren Verlauf einer SARS- CoV-2 Infektion zu entwickeln. Durch das fehlregulierte Immunsystem und durch die mit dem Krankheitsbild verbundenen vielen körperlichen Einschränkungen treten bei MS Pat. häufiger schwere Infektionen auf. Eine Anti-CD20-Antikörpertherapie depletiert vor allem B-Zellen, zu einem geringen Teil auch T-Zellen. Mit dieser immunsupprimierenden Therapie haben Pat. ein nochmals erhöhtes Infektionsrisiko. Zur B-Zell depletierenden Therapie (BZDT) werden aktuell Ocrelizumab, Ofatumumab und Rituximab verwendet. Durch eine Impfung könnten die MS Pat. mit BZDT vor einer SARS-CoV-2 Infektion geschützt werden bzw. ein schwerer Verlauf durch sie verhindert werden. Die Beurteilung der Effektivität einer Impfung kann durch die Analyse der B-Zell spezifischen und T-Zell spezifischen Impfantwort untersucht werden. Ziel der Studie ist es, herauszufinden, ob Pat. trotz der MS-Erkrankung und einer Anti-CD20 Antikörpertherapie eine Impfantwort entwickeln und ob die Pat. dadurch von einer SARS- CoV2-Impfung profitieren.:Abkürzungsverzeichnis Abbildungsverzeichnis Tabellenverzeichnis 1. Einleitung 1.1 Multiple Sklerose 1.1.1 Epidemiologie 1.1.2 Ätiologie und Risikofaktoren 1.1.3 Pathophysiologie 1.1.4 Symptome 1.1.5 Verlaufsformen 1.1.6 Diagnostik 1.1.7 Prognosefaktoren 1.1.8 Therapie 1.2 SARS-CoV-2 1.2.1 Epidemiologie 1.2.2 Ätiologie und Risikofaktoren 1.2.3 Infektion und ihre Immunantwort 1.2.4 Impfung 2. Fragestellung und Zielsetzung 3. Material und Methode 3.1 Einschlusskriterien 3.2 Methode 3.2.1 B-Zell Antwort 3.2.2 T-Zell Antwort 3.3 Statistik 3.4 Pat.kollektiv 4. Ergebnisse 4.1 Ergebnisse nach der Grundimmunisierung 4.1.1 B- und T-Zell Antwort nach der Grundimmunisierung 4.1.2 Einfluss einer SARS-CoV-2-Infektion auf die B- und T-Zell Antwort nach der Grundimmunisierung 4.2 Ergebnisse nach der Booster Impfung 4.2.1 B- und T-Zell Antwort nach der Booster Impfung 4.2.2 Einfluss einer SARS-CoV-2-Infektion auf die B- und T-Zell Antwort nach der Booster Impfung 4.3 SARS-CoV-2 spezifische B- und T-Zell Antwort im Verlauf 4.4 Bedeutung des zeitlichen Beginns einer BZDT auf die SARS-CoV-2 spezifische Impfantwort 5. Diskussion 6. Zusammenfassung 7. Summary 8. Literaturverzeichnis 9. Danksagung 10. Anhang (einschließlich Originalpublikationen) / Patients with multiple sclerosis generally face an elevated risk of experiencing a severe course of SARS-CoV-2 infection. This heightened susceptibility results from the dysregulated immune system and various physical limitations associated with the disease. Anti-CD20 therapy primarily leads to B-cell depletion and, to a lesser extent, T-cell depletion. Consequently, patients undergoing BCDT, which includes ocrelizumab, ofatumumab, and rituximab, are at an even greater risk of infection due to this immunosuppressive therapy. Vaccination emerges crucial of protecting MS patients undergoing BCDT from SARS-CoV-2 infection or mitigating the severity of the disease. The effectiveness of a vaccination can be assessed by analyzing the B-cell specific and T-cell specific vaccination response. The study aims to ascertain whether patients with MS, despite the disease and anti-CD20 antibody therapy, develop a vaccination response and whether they indeed benefit from a SARS-CoV-2 vaccination.:Abkürzungsverzeichnis Abbildungsverzeichnis Tabellenverzeichnis 1. Einleitung 1.1 Multiple Sklerose 1.1.1 Epidemiologie 1.1.2 Ätiologie und Risikofaktoren 1.1.3 Pathophysiologie 1.1.4 Symptome 1.1.5 Verlaufsformen 1.1.6 Diagnostik 1.1.7 Prognosefaktoren 1.1.8 Therapie 1.2 SARS-CoV-2 1.2.1 Epidemiologie 1.2.2 Ätiologie und Risikofaktoren 1.2.3 Infektion und ihre Immunantwort 1.2.4 Impfung 2. Fragestellung und Zielsetzung 3. Material und Methode 3.1 Einschlusskriterien 3.2 Methode 3.2.1 B-Zell Antwort 3.2.2 T-Zell Antwort 3.3 Statistik 3.4 Pat.kollektiv 4. Ergebnisse 4.1 Ergebnisse nach der Grundimmunisierung 4.1.1 B- und T-Zell Antwort nach der Grundimmunisierung 4.1.2 Einfluss einer SARS-CoV-2-Infektion auf die B- und T-Zell Antwort nach der Grundimmunisierung 4.2 Ergebnisse nach der Booster Impfung 4.2.1 B- und T-Zell Antwort nach der Booster Impfung 4.2.2 Einfluss einer SARS-CoV-2-Infektion auf die B- und T-Zell Antwort nach der Booster Impfung 4.3 SARS-CoV-2 spezifische B- und T-Zell Antwort im Verlauf 4.4 Bedeutung des zeitlichen Beginns einer BZDT auf die SARS-CoV-2 spezifische Impfantwort 5. Diskussion 6. Zusammenfassung 7. Summary 8. Literaturverzeichnis 9. Danksagung 10. Anhang (einschließlich Originalpublikationen)

京都大学 / 新制・課程博士 / 博士(薬学) / 甲第23844号 / 薬博第851号 / 新制||薬||242(附属図書館) / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 山下 富義, 教授 石濱 泰, 教授 金子 周司 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Introducción. La pandemia por coronavirus 2019 (COVID-19) se ha extendido en más de 100 países. La información específica sobre su comportamiento en el embarazo y parto sigue siendo limitada. Objetivo. Describir las características materno perinatales de pacientes gestantes con COVID-19 en un hospital terciario. Métodos. Estudio descriptivo. Se seleccionó todas las gestantes hospitalizadas por el servicio de emergencia de gineco-obstetricia entre el 24 de marzo y el 07 de mayo del 2020 y que tuvieron diagnóstico de infección por SARS-CoV-2, mediante la prueba rápida o la prueba RT-PCR. Se revisó la historia clínica y registros hospitalarios buscando variables sociodemográficas, antecedentes, manifestaciones clínicas, serología materna, complicaciones obstétricas, vía de parto y aspectos perinatales. Resultados. Se encontró 41 casos de pacientes con diagnóstico de SARS-CoV-2. Un 9,2% tuvo resultado de prueba rápida positiva, Los síntomas más comunes fueron tos en 84,6%, fiebre en 76,9% y dolor de garganta en 61,5%. Un 68.2% estuvo asintomática, 19,5% tuvo enfermedad leve y 7,3% moderada. Dos casos de neumonía severa requirieron ventilación no invasiva. No se registró muerte materna. 21,7% de los partos fue vía vaginal y 78,3% por cesárea. Hubo un caso de neonato por parto vaginal con PCR positivo al octavo día de vida. Conclusiones. Hubo un alto porcentaje de pacientes gestantes PCR positivas asintomáticas. Es necesario implementar el tamizaje universal en parturientas en el protocolo de flujo de gestantes en cada institución. / Introduction: The pandemic of coronavirus disease 2019 (COVID-19) has spread to more than 100 countries. Specific information about its behavior in pregnancy is still limited. Objective: To describe the maternal and perinatal characteristics of pregnant patients infected with COVID-19 and their newborns in a tertiary referral hospital. Methods: Descriptive study. Subjects were all pregnant patients admitted to the OB/ GYN Emergency Department of the Edgardo Rebagliati Martins National Hospital from March 24 to May 7, 2020, who were diagnosed with SARS-CoV-2 infection by rapid test or by RT-PCR test. Medical and hospital records were reviewed to retrieve sociodemographic data, patient’s history, clinical manifestations, maternal serology, obstetric complications, delivery mode and perinatal aspects. Results: 41 patients diagnosed with SARS-CoV-2 were identified. 9.2% of all admissions had a positive rapid test. The most common symptoms were cough in 84.6%, fever in 76.9% and sore throat in 61.5%. 68.2% of the patients were asymptomatic, 19.5% had mild illness and 7.3 %, moderate. 2 cases progressed to severe pneumonia requiring non-invasive ventilation. No maternal deaths were recorded. 21.7% were vaginal deliveries, while 78.3% were C-sections. One baby born in a vaginal delivery had a positive PCR result on day 8. Conclusions: A large percentage of asymptomatic pregnant patients had a positive PCR test. Implementing universal screening among patients in l flow protocol is necessary for all institutions.

Se reporta el caso de un varón de 62 años quien presentó tos y dolor abdominal por dos semanas, con hallazgos tomográficos pulmonares compatibles con probable infección por SARS-CoV-2, que recibió tempranamente corticoterapia a dosis altas y de manera ambulatoria. El paciente presentó evolución tórpida, fue hospitalizado y falleció en el posoperatorio inmediato por un cuadro de abdomen agudo quirúrgico. El estudio anatomopatológico mostró estructuras parasitarias con características compatibles con amebas, como causa de una colitis aguda fulminante complicada, con perforación múltiple y peritonitis aguda. La colitis aguda fulminante por amebiasis intestinal en el contexto de un paciente con probable COVID-19 no había sido reportada en el Perú. Resulta importante resaltar la presentación fulminante con desenlace fatal de esta infección parasitaria prevalente en nuestro medio, en el contexto del uso de corticoides ante una probable infección pulmonar por COVID-19. / We report the case of a 62-year-old male with cough and abdominal pain for two weeks, associated with pulmonary tomographic findings compatible with probable infection by SARS-CoV-2, and who received high doses of early corticotherapy as an outpatient. The patient showed clinical deterioration, was hospitalized and died in the immediate postoperative period due to acute surgical abdomen. The anatomopathological study showed parasitic structures with characteristics compatible with amebae, which was pointed to as the cause of a complicated acute fulminant colitis, with multiple perforations and acute peritonitis. Acute fulminant colitis due to intestinal amebiasis in the context of a patient with probable COVID-19 had not been previously reported in Peru. It is important to highlight the fulminant presentation with fatal outcome of this prevalent parasitic infection, in the context of corticosteroids use in a probable SARS-CoV-2 pulmonary infection.

SARS-CoV-2 började cirkulera i slutet av 2019 och ungefär tre månader senare klassades utbrottet som en pandemi. Idag, ungefär ett och ett halvt år efter virusutbrottet kämpar människor i hela världen fortfarande för att ta sig ur kriserna som pandemin orsakar. Trots stora forskningsinsatser är det ännu mycket som är ovisst kring virusets uppkomst. Olika teorier försöker bevisas men till dagens datum är det inte bekräftat var SARS-CoV-2 har sitt ursprung. Det verkar troligt att SARS-CoV-2 har en gemensam förfader med β-coronaviruset RaTG13. Det är sannolikt att fladdermus tillsammans med minst en mellanvärd har varit inblandad i uppkomsten av viruset. Viruset har gett upphov till flera varianter som spridit ut sig i världen. Globalt samarbete med övervakning av mutationer och varianter är viktigt för hur utvecklingen av pandemin ska fortgå. Med SARS-CoV-2 och Covid-19-pandemin som utgångspunkt analyseras möjligheter och utmaningar med undervisning i gymnasieskolan om aktuella stora händelser. / The outbreak of SARS-CoV-2 occurred at the end of 2019 and three months later, it was declared as a pandemic. Today, roughly one and a half years later, people across the world are still struggling to get out of the crises caused by the pandemic. Despite the huge efforts within science, much is still uncertain about the virus’ origin. Different theories are trying to be proven by scientists but to date, there is no confirmation from where the virus has its origin, nor whether one or several intermediate hosts have been involved. It seems likely that SARS- CoV-2 has a common ancestor with the bat β-coronavirus RaTG13. Therefore, it is probable that bats with at least one other intermediate host have been involved in the origin of the virus. Several variants have emerged and spread throughout the world. Global cooperation in regards of surveilling mutations and variants is of great importance regarding the development of the pandemic. Using SARS-CoV-2 and the Covid-19 pandemic as a focal point, there is an analysis showing opportunities and challenges when teaching big contemporary events.

Self-medication impacts both negatively and positively the health of people, which has become evident during the COVID-19 pandemic. The study aimed to assess the prevalence of self-medicated drugs used for respiratory symptoms, as COVID-19 preventive, for its symptoms or once tested positive. To determine the perception of symptom relief and demographic variables that promote self-medication in Peru. We performed a cross-sectional, analytical, multicenter study in 3792 study respondents on the use, the reason for use, and perception of relief after the use of six drugs during the quarantine period. An online questionnaire was developed, pretested and submitted to the general public. Multivariable logistic regression was used to ascertain factors that influence an individual's desire to self-medicate, associations were considered significant at p < 0.05 and using region (coast, mountain and jungle) as cluster group. The majority of respondents self-medicated with acetaminophen for respiratory symptoms and mainly because they had a cold or flu. It was observed that all the surveyed drugs (acetaminophen, ibuprofen, azithromycin, penicillin, antiretrovirals and hydroxychloroquine) were consumed for various symptoms including: fever, fatigue, cough, sneezing, muscle pain, nasal congestion, sore throat, headache and breathing difficulty. Over 90% of respondents perceived relief of at least one symptom. Multivariable logistic regression showed that older people have a higher frequency of antiretroviral self-medication, respondents who currently have a job had a higher frequency of penicillin self-medication, and that respondents from the Andes consumed less acetaminophen, while the ones from the rainforest consumed it more. There were significant percentages of self-medication, including drugs without sufficient scientific evidence. Age, region where one lived and job status were variables associated with self-medication frequency. Continuous awareness and sensitization about the risks of self-medication are warranted. / Revisión por pares

Objetivo: Describir las características demográficas, clínicas, laboratoriales y de tratamiento de pacientes hospitalizados por la COVID-19 y determinar los factores de riesgo de mortalidad hospitalaria. Materiales y métodos: Estudio de cohorte retrospectivo de pacientes adultos hospitalizados por la COVID-19. Se extrajeron datos demográficos, clínicos, laboratoriales y de tratamiento de las historias clínicas de pacientes que ingresaron al Hospital III Daniel Alcides Carrión de Tacna. Para el análisis de supervivencia se empleó el modelo de riesgos proporcionales de Cox y se calcularon los cocientes de riesgo instantáneos (HR) crudos y ajustados con sus respectivos intervalos de confianza al 95% (IC 95%). Resultados: Se evaluó a 351 pacientes, el 74,1% eran hombres; las comorbilidades más comunes fueron obesidad (31,6%), hipertensión (27,1%) y diabetes mellitus (24,5%). La mediana de tiempo de hospitalización fue 8 días (RIC: 4-15). El 32,9% falleció durante el seguimiento. El análisis multivariado mostró un aumento del riesgo de morir asociado a la edad ≥65 años, HR = 3,55 (IC 95%: 1,70-7,40); al incremento de lactato deshidrogenasa >720 U/L, HR = 2,08 (IC 95%: 1,34-3,22); y a la saturación de oxígeno por debajo del 90%, principalmente cuando fue menor al 80%, HR = 4,07 (IC 95%: 2,10-7,88). Además, el uso de colchicina en el tratamiento tuvo un efecto protector, HR = 0,46 (IC 95%: 0,23-0,91). Conclusiones: Los factores de riesgo de muerte por la COVID-19 incluyeron ser mayor de 65 años, tener saturación de oxígeno menor de 90% y elevación del lactato deshidrogenasa >720 U/L; el tratamiento con colchicina podría mejorar el pronóstico de los pacientes.

Title: Distance form of teaching physical education during the pandemic SARS- CoV-2. Aims: The aim of this work was to determine the course and provision of physical education in the time of the SARS-CoV-2 pandemic from 1 January 2020 to 31 December 2020. Methods: An online questionnaire was used to write the work, which was shared with teachers via social networks and via email. CAWI method was used for data collection. The data were subsequently processed using MS Excel 2013. Results: The results show that in the spring the teaching of physical education took place much less and less often than in the autumn. In the spring, the teachers did not yet have such technical equipment compared to the autumn, and the teaching took place mainly in an offline form. In the autumn, more teachers taught online, focusing mainly on motivating children to move. In the spring part, the teaching was more theoretically focused. Respondents agreed that a failure in physical education will have a major impact on children's development in the future. Keywords: SARS-CoV-2, distance learning, physical education, government measures, pandemic

Background: The epidemiology of SARS-CoV-2 infection in the pediatric population, with a focus on racial and ethnic disparities and impact of societal public health measures, remains poorly understood. Methods: This large observational study used electronically abstracted data from pediatric (≤ 19 years of age) patients who received a molecular test for SARS-CoV-2 at a UMass Memorial Health Care (UMMHC) site between March 8, 2020 and April 3, 2021 which was further supplemented by manual chart review of a subset of pediatric SARS-CoV-2 cases. Multivariable logistic regression models with interaction terms were used to identify risk factors for SARS-CoV-2 infection. Segmented regression analysis using Poisson models was used to estimate the effect of public health measures on the weekly incidence of SARS-CoV-2 infection. Results: A total of 25,426 unique pediatric patients were tested for SARS-CoV-2 among whom 2,920 (11.5%) tested positive. The average age of those who tested positive was 10.8 years (SD: 5.8) and 48.1% were female. In the subset analysis, nearly three-quarters (75.9%) of SARS-CoV-2 diagnoses occurred through a telephone encounter, meaning that the child was not physically examined by a provider prior diagnosis and only 2.0% were admitted for inpatient care at diagnosis. Results of multivariable regression revealed that children or parents who self-reported Black race, Hispanic ethnicity, and non-English primary language were associated with approximately twice the odds of testing positive in comparison with White or English-speaking patients. Furthermore, increasing age was associated with increased odds of testing positive for SARS-CoV-2 (aOR: 1.1 (1-4 years), 1.2 (5-9 years), 1.4 (10-14 years), 1.6 (15-17 years), 1.7 (18-19 years)). However, this association between age and positivity rate, varies by race/ethnicity and primary language such that Non-Hispanic Black, Hispanic, and non-English speaking children had markedly greater odds of testing positive during adolescence in comparison to Non-Hispanic White and English-speaking counterparts. Results from segmented regression analysis demonstrated a decline in weekly incidence of cases 9.9% (95% CI: 7.8 – 11.9) after the Massachusetts state mask mandate was implemented. During the winter holidays, the rate of increase in the weekly incidence of cases was 12.1% (95% CI: 11.9 – 12.3) in this pediatric population. Conclusions: Many SARS-CoV-2 cases have been diagnosed at UMMHC sites and notable racial/ethnic disparities exist that vary based on patient age. Public health measures are effective at preventing transmission of SARS-CoV-2 among children.

During the past two years, the pandemic of the SARS-CoV-2 virus has impacted where a big share of the world’s employees conducts their work. Governments around the world have encouraged people to stay at home as much as possible, in the hope of slowing down the infection rate of the virus. Companies around the world have therefore encouraged their employees to work from home. The change has been rapid and unusual for a lot of people. The purpose of this thesis is to examine what the effects of working from home has had on employees and what parameters may make it sustainable long-term. When investigating this matter further, a set of sub-questions has been identified in hope to obtain a deeper understanding of the topic and to answer the question of How can working from home be sustainable long-term? This paper is a qualitative research that follows an inductive approach. The literature review provides relevant theoretical background, which has then been the foundation for the analysis and conclusion. The theories provided covers leadership, motivation, efficiency, gender equality, government support, and internationalization. The conceptual framework then provides a deeper understanding of how each of these theories relates to the main question and its sub-questions. The authors have then examined secondary data such as articles from trusted journals as well as government records in a systematic literature review. An analysis of the findings in the systematic literature review in correlation to the theories has then been made to each sub-question. The concluding chapter then ties the thesis by answering the main question of this subject.