Sykdommer som skyldes infeksjoner er den hyppigste årsak til død på verdensbasis. Nye infeksiøse agens, slik som SARS-CoV-2, må gjennomgå mye forskning for å få kunnskap om virusets biologi og evne til å fremkalle sykdom (patogenese) i verten. For å kunne få en god mekanistisk forståelse av sykdomsprosessen trenges det å identifisere risikofaktorer for alvorlig sykdom og finne hvilken terapi som gir effekt, samt undersøke virusets formeringsevne og dynamikk i tillegg til vertens respons. Ved å studere immun responser over tid i verten og hvilke faktorer som virker inn på dette, kan det gi kunnskap om individers mottakelighet.
På Oslo Universitetssykehus, startet vi opp "Norwegian SARS-CoV-2 study", som er en observasjonsstudie på det nyoppdagete SARS-CoV-2, coronaviruset som forårsaker COVID-19 infeksjon. Studien ble raskt godkjent i Regional Etisk komite februar 2020, og etterpå var inklusjon igang med de første bekreftede COVID-19 tilfellene som trengte sykehus behandling i starten av pandemien.
Studien forventes å skaffe til veie mye kunnskap om forløpet av COVID-19 infeksjon, samt i tillegg å generere mye data om viruset og dets smittemåte.
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.