An integrated clinical and genetic model for predicting risk of severe COVID-19

Dite, G. S.; Murphy, N. M.; Allman, R.

Background: Age and gender are often the only considerations in determining risk of severe COVID-19. There is an urgent need for accurate prediction of the risk of severe COVID-19 for use in workplaces and healthcare settings, and for individual risk management. Methods: Clinical risk factors and a panel of 64 single-nucleotide polymorphisms were identified from published data. We used logistic regression to develop a model for severe COVID-19 in 1,582 UK Biobank participants aged 50 years and over who tested positive for the SARS-CoV-2 virus: 1,018 with severe disease and 564 without severe disease. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Results: A model incorporating the SNP score and clinical risk factors (AUC=0.786) had 111% better discrimination of disease severity than a model with just age and gender (AUC=0.635). The effects of age and gender are attenuated by the other risk factors, suggesting that it is those risk factors -- not age and gender -- that confer risk of severe disease. In the whole UK Biobank, most are at low or only slightly elevated risk, but one-third are at two-fold or more increased risk. Conclusions: We have developed a model that enables accurate prediction of severe COVID-19. Continuing to rely on age and gender alone to determine risk of severe COVID-19 will unnecessarily classify healthy older people as being at high risk and will fail to accurately quantify the increased risk for younger people with comorbidities.