Coronavirus disease 2019 (covid-19) är en smittsam infektionssjukdom som orsakas av viruset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sedan sjukdomens utbrott i december 2019 har viruset spridits globalt och infekterat fler än 270 miljoner människor världen över. Majoriteten av de som insjuknar i covid-19 får lindriga till måttliga besvär, men en liten del blir allvarligt sjuka och behöver sjukhusvård. Bland de patienter som blir allvarligt sjuka i covid-19 diagnostiseras en betydande del i det akuta skedet med sväljsvårigheter, eller dysfagi. Föreliggande studie bestod i en retrospektiv journalgranskning, som en del av ett kvalitetssäkringsarbete inom Region Gävleborg. Syftet med studien var att undersöka hur sväljsvårigheter kan manifesteras hos personer som vårdas på sjukhus till följd av covid-19 och som remitterats till logoped för bedömning och åtgärder. 60 deltagare inkluderades i studien, varav 17 var kvinnor och 43 var män. Resultaten visar att förekomsten av dysfagi var hög i det akuta skedet, där 42 deltagare (70 %) bedömdes ha dysfagi vid första logopedbedömning. Många deltagare återhämtade sig från sin dysfagi under vårdtiden, men 12 deltagare (20 %) hade kvarstående dysfagi vid utskrivning. Behovet av nutritionsstöd och andningsstöd under vårdtiden var stort. Vanliga fynd under de kliniska sväljbedömningarna var hosta, trögutlöst sväljning och nedsatt oral bearbetning. Deltagarna erhöll logopediska rekommendationer främst gällande anpassad kost, sittställning och munvård. Deltagarnas sväljförmåga skattades med Functional Oral Intake Scale (FOIS) vid första logopedbedömning och vid utskrivning. Vid första bedömning rekommenderades en majoritet av deltagarna anpassad kost (FOIS 1–6) och medelvärdet för FOIS var 3,5 ± 2,1. Vid utskrivning hade de flesta återgått till normalkost (FOIS 7) och medelvärdet för FOIS var 6,0 ± 1,8 (p < 0,001). Denna studie visar att en majoritet av de som vårdats på sjukhus till följd av covid-19 i Region Gävleborg och som remitterats till logoped, uppvisade dysfagi i det akuta skedet men kunde vid utskrivning äta normalkost. Behovet av mer forskning och vidare analyser av hur sväljsvårigheter manifesteras och upplevs hos patientgruppen är fortsatt stort. / Coronavirus disease 2019 (COVID-19) is a contagious infectious disease caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak in December of 2019, the virus has spread globally and infected more than 270 million people worldwide. The majority of people infected with COVID-19 will have mild to moderate symptoms, but some will suffer from severe illness which requires hospital care. Many of those who experience severe illness from COVID-19 are diagnosed with swallowing difficulties, or dysphagia, in the acute stage. This study consisted of a retrospective medical chart review and is part of a review of quality control in Region Gävleborg. The aim of the study was to investigate how swallowing difficulties manifest in people who require hospital care due to COVID-19 and who have been referred to the Speech and Language Therapy department. 60 participants were included in the study, of whom 17 were women and 43 were men. The results show that the prevalence of dysphagia was high in the acute stage, where 42 participants (70%) were diagnosed with dysphagia during the first SLT assessment. Many participants recovered from their dysphagia during their hospital stay, but 12 participants (20%) had persistent dysphagia at discharge. The need for nutritional and respiratory support was high. Common findings from the clinical swallowing assessments were coughing, difficulty initiating swallowing as well as affected oral processing. Common SLT recommendations included modified consistencies, posture and oral care. Swallowing ability was graded with the Functional Oral Intake Scale (FOIS) at first SLT assessment and at discharge. At first SLT assessment a majority of the participants were recommended a modified diet (FOIS 1-6) and the average FOIS was 3.5 ± 2.1. At discharge most participants had returned to a normal diet (FOIS 7) and the average FOIS was 6.0 ± 1.8 (p < 0,001). This study shows that a majority of the people who were hospitalized due to COVID-19 in Region Gävleborg and who were referred for an SLT evaluation, had dysphagia in the acute stage and recovered from their swallowing difficulties before discharge. More research and further analyses of how swallowing difficulties manifest in patients hospitalized due to COVID-19 is still needed.

[pt] A pandemia do COVID-19 teve impactos sem precedentes em indivíduos e comunidades em todo o mundo. Uma questão de grande preocupação é o impacto da pandemia na saúde mental. O isolamento, o medo e a incerteza causados pelo vírus levaram ao aumento das taxas de ansiedade, depressão e outros problemas de saúde mental. As preocupações com o aumento da prevalência de distúrbios psicológicos já estão levando os países a incluir a saúde mental e o apoio psicossocial em seus planos de resposta à COVID-19, mas, apesar disso, permanecem grandes lacunas e preocupações. Os múltiplos estressores desencadeados pelo vírus, somados às graves interrupções nos serviços públicos, deixaram sérias lacunas no atendimento de quem mais precisa. Além do agravamento e generalização de condições de saúde mental pré-existentes, agora também há a necessidade de acomodar questões recém-desenvolvidas. Nosso objetivo é, portanto, investigar os principais motivos que levaram os pacientes do Serviço de Psicologia Aplicada da PUC-Rio a buscar tratamento psicológico antes (2019) e durante a pandemia (2020 e 2021). Através de uma análise lexical dos formulários de demanda psicológica, pretendemos rastrear as possíveis transições e agravos entre demandas psicológicas de adultos (artigo 1) e famílias (artigo 2) utilizando o software IRaMuTeQ e o método Reinert, que analisa qualitativa e quantitativamente as transcrições relatórios. Por meio desse recurso de análise, é possível começar a mapear e investigar as queixas subjetivas desses pacientes, sua evolução e suas correlações. / [en] The COVID-19 pandemic has had unprecedented impacts on individuals and communities around the world. A matter of great concern is the impact of the pandemic on mental health. The isolation, fear and uncertainty caused by the virus has led to increased rates of anxiety, depression and other mental health issues. Concerns about the increasing prevalence of psychological disorders are already leading countries to include mental health and psychosocial support in their COVID-19 response plans, but despite this, major gaps and concerns remain. The multiple stressors triggered by the virus, in addition to the severe interruptions in public services, have left serious gaps in the care of those who need it most. In addition to the worsening and generalization of pre-existing mental health conditions, there is now also a need to accommodate newly developed issues. Our objective is therefore to investigate the main reasons that led patients from the Service of Applied Psychology at PUC-Rio to seek psychological treatment before (2019) and during the pandemic (2020 and 2021). Through a lexical analysis of the psychological demand forms, we intend to trace the possible transitions and aggravations between psychological demands of adults (article 1) and families (article 2) using the IRaMuTeQ software and the Reinert method, which qualitatively and quantitatively analyzes the transcribed reports. Through this analysis resource, it is possible to start mapping and investigating the subjective complaints of these patients, their development and their correlations.

Dependent on the excretion pattern, wastewater monitoring of viruses can be a valuable approach to characterizing their circulation in the human population. Using polyethylene glycol precipitation and reverse transcription-quantitative PCR, the occurrence of RNA of SARS-CoV-2 and influenza viruses A/B in the raw wastewater of two treatment plants in Germany between January and May 2022 was investigated. Due to the relatively high incidence in both exposal areas (plant 1 and plant 2), SARS-CoV-2-specific RNA was determined in all 273 composite samples analyzed (concentration of E gene: 1.3 × 10⁴ to 3.2 × 10⁶ gc/L). Despite a nation-wide low number of confirmed infections, influenza virus A was demonstrated in 5.2% (concentration: 9.8 × 10² to 8.4 × 10⁴ gc/L; plant 1) and in 41.6% (3.6 × 10³ to 3.0 × 10⁵ gc/L; plant 2) of samples. Influenza virus B was detected in 36.0% (7.2 × 10² to 8.5 × 10⁶ gc/L; plant 1) and 57.7% (9.6 × 10³ to 2.1 × 10⁷ gc/L; plant 2) of wastewater samples. The results of the study demonstrate the frequent detection of two primary respiratory viruses in wastewater and offer the possibility to track the epidemiology of influenza by wastewater-based monitoring.

In der vorliegenden Arbeit wurden modernste Multiplexing-Ansätze der quantitativen Proteomanalyse angewandt, um das neuartige Virus SARS-CoV-2 zu untersuchen, den Erreger der globalen COVID-19 Pandemie, die Ende 2019 begann. Trotz enormer internationaler Anstrengungen zur Erforschung dieser Krankheit sind viele Aspekte der grundlegenden Virusbiologie, Virus-Wirt-Interaktionen und der COVID-19-Pathophysiologie noch immer unbekannt. Dies verhindert die Entwicklung gezielter Behandlungen, insbesondere für COVID-19-Patienten mit schwerem Verlauf. Im ersten Teil dieser Arbeit wurde die Infektionsdynamik in lungenähnlichen Zelllinien untersucht. Der Vergleich von SARS-CoV mit SARS-CoV-2-Infektion in Zellen mit niedriger ACE2 Expression ermöglichte es, die Rolle anderer Membranproteine ​​als Virus Eintrittsfaktoren neu zu bewerten. In SARS-CoV-2 infizierten Calu-3-Zellen konnten Reaktionen der Wirtszellen beobachtet werden, die die Interaktion zwischen viralen Proteinen und Proteikinasen der Wirtszelle vermitteln. Im nächsten Teil wurde die angeborene Immunantwort des Wirts auf das Virus untersucht. Primäre, aus Blut isolierte Monozyten, die mit SARS-CoV-2 behandelt wurden, wiesen eine spezifische Protein-Signatur auf, die auf eine Polarisierung der Zellen zu einem profibrischen Makrophagen-Phänotyp hindeutet. Weitere Analysen zeigten, dass dieser Prozess weitgehend unabhängig von bekannten antiviralen Reaktionen und viraler RNA-Sensoren in Monozyten abläuft. Die durch das Virus hervorgerufene Phosphoproteom-Signatur deutet an, dass die profibrotische Polarisierung durch die kombinierte Wechselwirkung von viralen Proteinen und Infektionsnebenprodukten mit Wirtsrezeptoren induziert wurde. Zusammenfassend liefert diese Arbeit einen wertvollen Beitrag zur Aufklärung von Mechanismen, die zu einem schweren COVID-19 Verlauf führen können und hebt dabei die Bedeutung von Proteomanalysen in der Erforschung viraler Erkrankungen hervor. / In this thesis, we used cutting-edge multiplexed quantitative proteomics and phosphoproteomics approaches to study the virus SARS-CoV-2. The newly emerged betacoronavirus is the causative agent of the global pandemic of COVID-19 that began in late 2019. Despite the tremendous research effort in studying this disease, many aspects of the basic viral biology, virus-host interactions and COVID-19 pathophysiology still remain obscure. This prevents the development of targeted treatments, especially for severe COVID-19 patients. In the first part of this thesis, we studied infection dynamics in lung-like cell lines. Comparison between SARS-CoV and SARS-CoV-2 infections in low-ACE2-expressing cells allowed us to re-evaluate the role of other membrane proteins as entry factors. In Calu-3 cells, we could observe host responses mediating the interactions between viral proteins and host kinases. Next, we focused on the innate immune response of the host to the virus. Ex vivo monocytes treated with SARS-CoV-2 exhibited a specific proteomic signature indicating a polarization toward a profibric macrophage phenotype. Further dissection of this response revealed it to be largely independent from the viral RNA sensing and antiviral response cellular mechanisms. Furthermore, the specific phosphoproteomics signature induced by the virus indicated that the profibrotic polarization was induced by the combined interaction between viral proteins and infection byproducts with host receptors. In summary, this thesis shows the power of mass spectrometry based proteomics to study the complex dynamics between viruses and host cells. Furthermore, we uncovered a potential mechanism contributing to the development of severe COVID-19.

Introduktion: SARS-CoV-2-pandemin resulterar i katastrofala både direkta och indirekta konsekvenser, speciellt i utvecklingsländer. Hälso- och sjukvårdspersonal påverkar samhällets åsikter, acceptans och beslutsfattande gällande vaccinering vilket gör att det är viktigt att förstå SARS-CoV-2-vaccintäckning, samt kunskap och attityd gentemot SARS-CoV-2-vaccin i denna målgrupp. Syfte: Att bestämma vilka variabler som är associerade med SARS-CoV-2-vaccination, samt kunskap och attityd gentemot det samma, hos hälso- och sjukvårdspersonal inom nivå 2- och 3-verksamheter i Nairobi. Metod: Ett kvantitativt frågeformulär delades ut till hälso- och sjukvårdspersonal som arbetar inom nivå 2- och 3-verksamheter i Nairobi. Data analyserades med hjälp av IBM SPSS Statistics 28. Chi-square test, Fisher’s exact test, t-test och envägs-ANOVA användes för att bestämma signifikant associerade variabler med SARSCoV-2 vaccinering, samt kunskap och attityd gentemot det samma. Resultat: Studien fann signifikanta samband mellan vaccinationsstatus och kunskapsindex (p=0,04). Gruppen sjuksköterskor, undersköterskor och läkare hade större sannolikhet att vara vaccinerade än andra yrkesgrupper (p=0,027). Positiva signifikanta samband hittades även mellan kunskapsindex och: ålder (p=0,031), att vara kvinna (p=0,029), erfarenhet (p=0,019), att vara vaccinerad (p=0,007), och attitydindex (p= <0,001). Studien fann även ett signifikant samband mellan kunskapsindex och subcounty (p=0,032). Dagoretti South, Embakasi East och Westlands hade de lägsta kunskapsindexen bland de subcounties som deltog i studien. Studien fann även positiva signifikanta samband mellan attitydindex och följande variabler: erfarenhet (p=0,022), att vara vaccinerad (p=<0,001) och kunskapsindex (p=<0,001). Resultaten visar även ett signifikant samband mellan attitydindex och yrke (p=0,025). Slutsats: Resultaten visar på hög vaccinationstäckning och en generellt positiv attityd. Dock belyser studien viktiga kunskapsluckor om COVID-19-vaccin hos deltagarna som bör adresseras i syfte att förbättrabåde kunskapsläget och vaccinationstäckningen i populationen. / Introduction: The pandemic caused by SARS-CoV-2 is having, and will have devastating indirect consequences, affecting developing countries in particular. The SARS-CoV-2 vaccine acceptance, knowledge and attitude among healthcare workers are important to understand since they influence public opinion, community vaccine acceptance, and decision-making regarding vaccination. Aim: To determine the associated variables with SARS-CoV-2 vaccine uptake, knowledge, and attitude among health workers in level 2 and 3 facilities in Nairobi.  Methods: A quantitative questionnaire was distributed to healthcare workers in level 2 and 3 health facilities in Nairobi. Data was analysed using IBM SPSS Statistics 28. Chi-square tests, Fisher’s exact tests, t-tests and one-way ANOVA tests were conducted to determine the associated variables with SARS-CoV-2 vaccine uptake, knowledge, and attitude. Results: A positively significant association was found between vaccine uptake and knowledge index (p=0,04). The group nurses, assistant nurses and physicians were more likely to be vaccinated than other health professions (p=0,027). A positively significant association was found between knowledge index and: age (p=0,031), being female (p=0,029), years of experience (p=0,019), being vaccinated (p=0,007), and attitude index (p=<0,001). A significant association was found between knowledge index and subcounty (p=0,032). Dagoretti South, Embakasi East and Westlands had the lowest knowledge indexes among the subcounties. A positively significant association was determined between attitude index and: years of experience (p=0,022), being vaccinated (p=<0,001), and knowledge index (p=<0,001). Health profession was also found to be significantly associated with attitude index (p=0,025). Conclusion: The results reflect a high vaccination uptake and a general positive attitude. However, the findings identified essential knowledge gaps regarding COVID-19 vaccines among the participants that should be addressed.

Purpose To investigate the relationship between the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children and the predominance of different SARS-CoV-2 variants of concern (VOC) over time. Methods In relation to the Alpha, Delta, and Omicron VOC phases of the pandemic, the risk of developing PIMS-TS was calculated by analyzing data for rtPCR-confirmed SARS-CoV-2 infections reported to the German statutory notification system, along with data captured by a separate, national PIMS-TS registry. Both overall infection rates and age group-specific ratios of PIMS-TS during the different pandemic phases were calculated using the Alpha period as the baseline. Results The PIMS-TS rate changed significantly over time. When the Alpha VOC was dominant [calendar week (CW) 11 in March–CW 31 in August 2021], the PIMS-TS rate was 6.19 [95% confidence intervals (95% CI) 5.17, 7.20]. When Delta prevailed (CW 32 in August 2021–CW 4 in January 2022), the rate decreased to 1.68 (95% CI 1.49, 1.87). During the Omicron phase (CW 5 in January–CW 16 in April 2022), the rate fell further to 0.89 (95% CI 0.79, 1.00). These changes correspond to a decreased PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, in comparison to the Alpha period. Rate ratios were nearly identical for all age groups. Conclusion The data strongly suggest an association between the risk for PIMS-TS and the prevailing VOC, with highest risk related to Alpha and the lowest to Omicron. Given the uniformity of the decreased risk across age groups, vaccination against SARS-CoV-2 does not appear to have a significant impact on the risk of children developing PIMS-TS.

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.