While older age and specific comorbidities are associated with higher risk of developing a severe form of COVID-19 caused by the coronavirus SARS-CoV-2, several patients without prior health conditions also develop severe forms of the disease. Coronaviruses are RNA viruses, characterized by high mutation and recombination rates. Viral factors, such as the emergence of more pathological variants during the course of the disease within an infected individual, targeting specifically the lungs, and scarcely if at all shed in the upper airways, may be a factor contributing to the severe cases in otherwise healthy individuals, as was shown in the influenza A H1N1 pandemic in 2009.

We hypothesize that SARS-CoV-2 variants with increased virulence will arise in a small proportion of the infected patients, spread to their lower respiratory tract, and will be associated with disease severity. These variants will potentially be identified in patients’ plasma, urine or faeces samples, and differ from the viral sequences detected in upper respiratory tract samples from the same patients, or from patients experiencing only mild symptoms.

In order to investigate the potential emergence of within-host pathological viral variants as a viral factor of severe COVID-19, we will retrospectively recruit a total of 150 patients from three distinct disease severity cohort, and we will investigate clinical samples, including respiratory tract, blood, urine, and fæcal samples for the presence of SARS-CoV-2. Patients will be included retrospectively from the COVID-19 patient cohort recruited in the general research biobank for internal medicine at Østfold Hospital Trust (REK 28861), based on their clinical characteristics. Whole-genome sequencing will be performed on virus positive samples, and the coronavirus genomes analysed for variation from the different sample types, taken at different time points, and from the different patient cohorts. These analyses will allow for the identification of specific viral signatures associated with increased virulence.