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 Dominique Salmon-Ceron, Institut Fournier, France
- Second opponent: Professor Bjørn Blomberg, University of Bergen, Norway
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, University of Oslo
Chair of the Defence
Associate Professor Lise Sofie H. Nissen Meyer, University of Oslo
Principal Supervisor
Lise Lund-Berven, Head of R&D section, Department of Microbiology and Infection Control, Akershus University Hospital
Summary
Long-lasting symptoms after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection are referred to as Post COVID-19 Condition (PCC). Defined by the presence of new or ongoing symptoms more than 12 weeks after acute infection, this condition is further characterized by hallmark symptoms such as fatigue, dyspnoea and cognitive impairment, and has a significant impact on daily functioning. The immunological mechanisms underlying the disease are debatable.
The purpose of this thesis was to explore the role of the immune system in PCC in adolescents and young adults. We conducted a prospective cohort study where participants testing positive for SARS-CoV-2 virus were followed for six months after inclusion. SARS-CoV-2 negative participants were used as controls. We used clinical, laboratory, and questionnaire data to classify participants in fatigued or non-fatigued groups. In addition, we conducted immune profiling using circulating peripheral immune markers, whole blood gene expression data and cytometry by time-of-flight (CyTOF).
We found elevated levels of three chemokines in the peripheral blood of previously SARS-CoV-2 infected individuals. There was, however, no association between these markers and fatigue. Meanwhile, transcriptome analysis revealed a higher expression of genes responsible for innate immunity against viral infections in SARS-CoV-2 positive participants with fatigue. CyTOF, on the other hand, showed common immune changes in SARS-CoV-2 positive and negative participants with fatigue complaints, but not in asymptomatic individuals. Here, elevated frequencies of Terminal NK cells, double negative B cells and CD4+ T cells with signatures of exhaustion could be detected in the participants with fatigue symptoms irrespective of triggering event.
The results suggest that an immunological pattern characterized by persistent pro-inflammatory state is associated with Post COVID-19 condition, and that there is potential shared pathophysiology with fatigue syndromes of other causes.
Additional information
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