Objective To assess the value of opportunistic biomarkers derived from chest CT performed at hospital admission of COVID-19 patients for the phenotypization of high-risk patients. Methods In this multicentre retrospective study, 1845 consecutive COVID-19 patients with chest CT performed within 72 h from hospital admission were analysed. Clinical and outcome data were collected by each center 30 and 80 days after hospital admission. Patients with unknown outcomes were excluded. Chest CT was analysed in a single core lab and behind pneumonia CT scores were extracted opportunistic data about atherosclerotic profile (calcium score according to Agatston method), liver steatosis (≤ 40 HU), myosteatosis (paraspinal muscle F Results The final cohort included 1669 patients (age 67.5 [58.5–77.4] yo) mainly men 1105/1669, 66.2%) and with reduced oxygen saturation (92% [88–95%]). Pneumonia severity, high Agatston score, myosteatosis, liver steatosis, and osteoporosis derived from CT were more prevalent in patients with more aggressive treatment, access to ICU, and in-hospital death (always p p = 0.0198) to predict patient death (AUC 0.815 vs 0.800; p = 0.001). Conclusion Opportunistic biomarkers derived from chest CT can improve the characterization of COVID-19 high-risk patients. Clinical relevance statement In COVID-19 patients, opportunistic biomarkers of cardiometabolic risk extracted from chest CT improve patient risk stratification. Key Points •In COVID-19 patients, several information about patient comorbidities can be quantitatively extracted from chest CT, resulting associated with the severity of oxygen treatment, access to ICU, and death. •A prediction model based on multiparametric opportunistic biomarkers derived from chest CT resulted superior to a model including only clinical variables in a large cohort of 1669 patients suffering from SARS- CoV2 infection. •Opportunistic biomarkers of cardiometabolic comorbidities derived from chest CT may improve COVID-19 patients’ risk stratification also in absence of detailed clinical data and laboratory tests identifying subclinical and previously unknown conditions.