Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study
Authors: Palmisano Anna , Gnasso Chiara , Cereda Alberto , Vignale Davide , Leone Riccardo , Nicoletti Valeria , Barbieri Simone , Toselli Marco , Giannini Francesco , Loffi Marco , Patelli Gianluigi , Monello Alberto , Iannopollo Gianmarco , Ippolito Davide , Mancini Elisabetta Maria , Pontone Gianluca , Vignali Luigi , Scarnecchia Elisa , Iannaccone Mario , Baffoni Lucio , Spernadio Massimiliano , de Carlini Caterina Chiara , Sironi Sandro , Rapezzi Claudio , Esposito Antonio 
Published: May 2023

Abstract
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 < 31.3 HU, M < 37.5 HU), and osteoporosis (D12 bone attenuation < 134 HU). Differences according to treatment and outcome were assessed with ANOVA. Prediction models were obtained using multivariate binary logistic regression and their AUCs were compared with the DeLong test.

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 < 0.05). A multivariable model including clinical and CT variables improved the capability to predict non-critical pneumonia compared to a model including only clinical variables (AUC 0.801 vs 0.789; 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.