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.

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

This thesis is about the politics and the possibilities of aetiology. Firstly, the possibilities. Does an infectious disease have one, single pathogenic cause or many, interacting causes? In the medical microbiological sciences, there is no definitive answer, one way or another, to this question: there, the conditions of aetiological possibility exist in a curious tension. Ever since the birth of the 'germ theory of disease' and the concomitant birth of the singular aetiological object, these conditions have allowed for the co-existence of a very different, and far less well understood kind of object: the multifactorial object. That SARS was caused by one, singular viral agent, a coronavirus (CoV), is now entrenched as microbiological fact. And yet, the curious thing about SARS is that the history of the 2003 outbreak is littered with moments at which the possibility of the multifactorial object presented itself to, and was actively considered by, medical microbiologists. So how did we get here - to SARS-CoV, an infectious disease that could be understood and storied in this, the most singular of ways? And what happened along the way to deny the multifactorial aetiological object any kind of existence at all? In an attempt to grapple with these questions, the thesis seeks to recover the possibility of the multifactorial object through a deep, ethnomethodological reading of the moments at which it flared up precise/y as a possibility for medical microbiologists investigating the outbreak. What emerges from that recovery operation is a sense that the multifactorial object was never actually ruled out or disproved in any way, but rather, was vanished. Put another way, the suggestion is that various medical microbiological practices and interventions, whilst establishing singularity, were serving, at the same time, to create an illusion of multifactorality's non-existence; an illusion behind which the issue of multifactorality, its possibility, could be discarded without ever having to be resolved, one way or the other. In the closing sections of this thesis a move is made towards suggesting that SARS-Co V, the singular disease, was the product of a choice-, a choice that was made to explore one aetiological possibility at the expense of another. And that is where the politics comes in. For if politics, the realm of the political, can be taken to arise in situations where various possibilities exist but not all possibilities can be chosen, then it follows that what this thesis provides is an opportunity to foreground the politics bound up with the practical doing of aetiology. As a result, and based on the experience of attempting to recover the vanished multifactorial object from the 2003 SARS outbreak, the thesis concludes with an attempt to inhabit the present in such a way as to make it possible to think, in a little more detail, about where aetiology, as understood by medical microbiologists, might be heading in the future: might recent shifts in practical, everyday, seemingly innocuous microbiological technique, have begun to make it easier to coax the multifactorial object out into a space of visibility? Might those shifts actually herald the crossing of an epistemological threshold in the medical sciences? And might the conditions of aetiological possibility be changing, and changing in ways that would drastically alter what it meant to speak of a 'disease', an 'infection' and a 'pathogen'?

This study conducted a framing research that analyzed coverage of the bird flu (avian flu) in China by two major American newspapers that are influential in China (The New York Times and Washington Post). The goal was to examine how these two prestigious newspapers frame the bird flu epidemic in China and how they represent the country in this international health crisis. This study employed textual analysis regarding the way bird flu news articles were framed in terms of problem definition, causal explanation, moral evaluation and solution recommendations in both newspapers. The study found the epidemic was framed as more than just a public health crisis. Multiple news frames were found in both newspapers' coverage of bird flu, depicting the event as a cultural, social and political crisis to the nation and to the world.

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

published_or_final_version / abstract / toc / Transport Policy and Planning / Master / Master of Arts in Transport Policy and Planning