Abstract
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 which enters the body via the angiotensin-converting enzyme 2 (ACE2) and altering its gene expression. Altered ACE2 plays a crucial role in the pathogenesis of COVID-19. Gene expression profiling, however, is invasive and costly, and is not routinely performed. In contrast, medical imaging such as computed tomography (CT) captures imaging features that depict abnormalities, and it is widely available. Computerized quantification of image features has enabled 'radiogenomics', a research discipline that identifies image features that are associated with molecular characteristics. Radiogenomics between ACE2 and COVID-19 has yet to be done primarily due to the lack of ACE2 expression data among COVID-19 patients. Similar to COVID-19, patients with lung adenocarcinoma (LUAD) exhibit altered ACE2 expression and, LUAD data are abundant. We present a radiogenomics framework to derive image features (ACE2-RGF) associated with ACE2 expression data from LUAD. The ACE2-RGF was then used as a surrogate biomarker for ACE2 expression. We adopted conventional feature selection techniques including ElasticNet and LASSO. Our results show that: i) the ACE2-RGF encoded a distinct collection of image features when compared to conventional techniques, ii) the ACE2-RGF can classify COVID-19 from normal subjects with a comparable performance to conventional feature selection techniques with an AUC of 0.92, iii) ACE2-RGF can effectively identify patients with critical illness with an AUC of 0.85. These findings provide unique insights for automated COVID-19 analysis and future research.