Norwegian SARS-CoV-2 study – Virological, clinical and immunological characterisation of inpatients during the COVID-19 outbreak

Infectious disease is the single biggest cause of death worldwide. New infectious agents, such as the SARS-CoV-2, require investigation to understand pathogen biology and pathogenesis in the host. In order to develop a mechanistic understanding of disease processes, such that risk factors for severe illness can be identified and treatments can be developed, it is necessary to understand pathogen characteristics associated with virulence, the replication dynamics and in-host evolution of the pathogen, the dynamics of the host response and transmission and factors underlying individual susceptibility. At Oslo University Hospital, we initiated the Norwegian SARS-CoV-2 study in January 2020, an observational study on the newly discovered emerging SARS- CoV-2, the coronavirus that causes COVID-19 infection. The study was quickly approved by the Regional Ethics Committee in February, so that inclusion of confirmed COVID-19 cases admitted at the hospital could start immediately during the pandemic including the first patients needing hospitalization. Hospitals from all four health regions joined our study and our national research network also joined the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) World Health Organization Clinical Characterization study where we contributed to sharing of COVID data globally. The study is anticipated to provide data on the course of the COVID-19 infection, as well as generating knowledge about the virus and its transmission.

According to plan we focused to 4 areas to improve inpatient outcomes that include: (1) clinical characterization of COVID-19 for early identification of risk factors for adverse outcome; (2) pathogenesis, including identification of prognostic markers and potential treatments; (3) host genetics to identify inherited risk factors; and (4) Long COVID. In these disciplines, our group has already published and submitted a total of 18 and 13 articles, respectively, in internationally recognized journals. As part of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), our work has contributed with COVID-19 clinical characterization data to a number of international reports. This work will continue but will also focus on microbiological aspects such as genotyping and sequencing of different materials (compartments) to uncover the characteristics and impact of different SARS-CoV-2 viral variants in the disease process.

The Norwegian SARS-CoV-2 study is designed as a multicenter hospital based cohort study that will allow us to analyse the disease outcome in relation to risk factors and intervention in a large material across institutions. All health regions in Norway are represented in this research initiative to minimise any bias in the material. To address the pathogenicity, we will investigate patients at different time points from inclusion in the cohort according to the ISARIC protocol to assess different outcomes by serial sampling and clinical data collection. We will use rapid syndrome-based point-of-care testing, Whole Genome Sequencing and Next Generation Sequencing to detect co-infections and for detailed studies of virological causes of severe outcome. Such novel sequencing techniques will be employed in collaboration with virologists at Wuhan Institute of Virology, Hubei, China, allowing for comparison with strains from the origin and start of the SARS-CoV-2 pandemic. The study will generate much needed knowledge on the clinical features of the infection, longterm morbidity and mortality and occurrence of co-infections and will describe the response to treatment, including supportive care and novel therapeutics. We will observe pathogen replication, excretion and evolution, within the host in various biological material. Further, we aim to investigate host immune responses over time during hospitalisation and at follow-up in relation to clinical outcome. This large study provides an excellent framework for a PhD fellowship focusing on the pathogenicity of SARS-CoV-2, co-infections and the study of virus mutations and dissemination in the patient over time and across cases using novel virological techniques. Furthermore, data on the whole genome of SARS-CoV-2 from our study will be compared with cases from Wuhan, the origin of the outbreak. The data will be shared with the international scientific community through the Oxford Database solution REDCap.