Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Jacob Odeberg, Karolinska Institutet, Sweden
- Second opponent: Researcher Markus Haug, Norwegian University of Science and Technology, Trondheim
- Third member and chair of the evaluation committee: Professor II Ida Gjervold Lunde, University of Oslo
Chair of the Defence
Professor Kjetil Retterstøl, University of Oslo
Principal Supervisor
Senior Researcher Tuva B. Dahl, Oslo University Hospital
Summary
In December 2019, a novel coronavirus was discovered in Wuhan. Later, at the end of February 2020, SARS-CoV-2 was discovered in Norway. The virus's emergence has led to an enormous load on healthcare systems in Norway and abroad. While most patients experience a mild or moderate disease, COVID-19 can also result in severe disease manifestations characterised by increasing shortness of breath, which can lead to respiratory failure and death. This doctoral thesis is based on clinical material from patients included in the NOR-Solidarity trial, which aimed to assess the effect of hydroxychloroquine and the antiviral medication remdesivir (REM) in hospitalised COVID-19 patients.
Blood samples were drawn during and after hospital admission. As immune cells are key regulators of the immune response, we also sampled immune cells in some patients.
In our first paper, we measured the expression of two chemokines, CCL19 and CCL21, known to regulate immune cell trafficking in blood samples. High admission levels of these chemokines correlated with mortality and respiratory failure. In two of our works, we investigated the role of extracellular matrix (ECM) remodelling in severe COVID-19. ECM remodelling is considered a vital process to facilitate infection clearance and proper wound healing. However, adverse remodelling can lead to tissue scarring and fibrosis. In the plasma of intensive care unit patients, we found an increase in ECM remodelling mediators associated with adverse outcomes such as respiratory failure and mortality. In parallel, we found up-regulation of several ECM-related genes in circulating immune cells. Finally, our analysis of immune cells revealed that REM decreased the immune cells' interferon response, potentially affecting its use as a therapeutic option in severe COVID-19. Our results indicate that while initially beneficial, excessive ECM remodelling, inflammation and immune dysregulation can be harmful in hospitalised COVID-19 patients.
Additional information
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