Aims This study aims to identify genetic factors contributing to the severity of covid19 infections. Finding such factors may help to identify and protect high risk individuals, but also provide important information for future anti-viral treatment and vaccine development. Ethical approval and funding: The study “Genetic predisposition for severe covid19” has been granted ethical approval (2020-02322 and 2020-05618). DNA from the study participants will be biobanked at the Department of Clinical Genetics, Karolinska University Hospital via Stockholms Medicinska Biobank (SMB). The study is funded by Hjärt-Lungfonden (grant numbers 20200733 and 20200372). Background and study plan The new coronavirus SARS-CoV-2, causing the disease Covid19, has as of December 2020 infected more than 65 million individuals worldwide and caused at least 1.5 million deaths. Sweden has been hard hit, registering more than 7000 deaths due to Covid19 during the last 9 months. Risk factors for developing severe Covid19-infection are foremost high age, but other co-morbidities such as hypertension, obesity, diabetes and respiratory disease also increase the risk of a severe infection. However, these risk factors only partly explain the disease-variability seen in Covid19. In Sweden, more than 3000 Covid19 patients, with a median age of only 62 years, have been treated at an intensive care unit (ICU), interestingly more than 70% of these ICU patients have been male. On the other end of the disease spectrum several studies suggest that a substantial proportion, often estimated to around 20-50%, of Covdi19 cases are asymptomatic. The skewed gender proportions and the wide clinical disease-spectrum suggest that genetic factors play a major role in disease severity. We will conduct a genome-wide association study comparing individuals (n≈2000) infected by SARS-CoV-2 and group them by disease severity, ranging from asymptomatic infections to respiratory failure and need of ICU-care. Because we will have information form patient journals precise phenotyping will be possible, but also key to understand the underlying genetics important for developing severe Covid19-infection. The study focuses on inviting patients <60 years of age without additional risk factors to decrease confounding and increase power. Our primary hypothesis is that polymorphisms within or near the gene ACE2 is of importance for disease severity, because SARS-CoV-2 need to bind the cell surface enzyme ACE2 to complete cell entry. There is also a strong correlation between the tissues ACE2 is expressed in and the tissues most strongly affected by covid-19, suggesting that ACE2 is of true importance. Furthermore, we will select certain individuals affected by severe Covid19 and perform whole exome and/or whole genome sequencing. In these selected individuals we will search for functional coding variants in the genomic regions implicated by the GWAS-analysis. By combining a GWAS approach with sequencing data in the same individuals the hope is to identify the actual gene and/or mechanism responsible for the association signals we hope to find.