Chest CT opportunistic biomarkers for phenotyping high-risk COVID-19 patients: a retrospective multicentre study.

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.

AI-SCoRE (artificial intelligence-SARS CoV2 risk evaluation): a fast, objective and fully automated platform to predict the outcome in COVID-19 patients.

PURPOSE: To develop and validate an effective and user-friendly AI platform based on a few unbiased clinical variables integrated with advanced CT automatic analysis for COVID-19 patients' risk stratification. MATERIAL AND METHODS: In total, 1575 consecutive COVID-19 adults admitted to 16 hospitals during wave 1 (February 16-April 29, 2020), submitted to chest CT within 72 h from admission, were retrospectively enrolled. In total, 107 variables were initially collected; 64 extracted from CT. The outcome was survival. A rigorous AI model selection framework was adopted for models selection and automatic CT data extraction. Model performances were compared in terms of AUC. A web-mobile interface was developed using Microsoft PowerApps environment. The platform was externally validated on 213 COVID-19 adults prospectively enrolled during wave 2 (October 14-December 31, 2020). RESULTS: The final cohort included 1125 patients (292 non-survivors, 26%) and 24 variables. Logistic showed the best performance on the complete set of variables (AUC = 0.839 ± 0.009) as in models including a limited set of 13 and 5 variables (AUC = 0.840 ± 0.0093 and AUC = 0.834 ± 0.007). For non-inferior performance, the 5 variables model (age, sex, saturation, well-aerated lung parenchyma and cardiothoracic vascular calcium) was selected as the final model and the extraction of CT-derived parameters was fully automatized. The fully automatic model showed AUC = 0.842 (95% CI: 0.816-0.867) on wave 1 and was used to build a 0-100 scale risk score (AI-SCoRE). The predictive performance was confirmed on wave 2 (AUC 0.808; 95% CI: 0.7402-0.8766). CONCLUSIONS: AI-SCoRE is an effective and reliable platform for automatic risk stratification of COVID-19 patients based on a few unbiased clinical data and CT automatic analysis.

The hidden interplay between sex and COVID-19 mortality: the role of cardiovascular calcification.

Recent clinical and demographical studies on COVID-19 patients have demonstrated that men experience worse outcomes than women. However, in most cases, the data were not stratified according to gender, limiting the understanding of the real impact of gender on outcomes. This study aimed to evaluate the disaggregated in-hospital outcomes and explore the possible interactions between gender and cardiovascular calcifications. Data was derived from the sCORE-COVID-19 registry, an Italian multicentre registry that enrolled COVID-19 patients who had undergone a chest computer tomography scan on admission. A total of 1683 hospitalized patients (mean age 67±14 years) were included. Men had a higher prevalence of cardiovascular comorbidities, a higher pneumonia extension, more coronary calcifications (63% vs.50.9%, p<0.001), and a higher coronary calcium score (391±847 vs. 171±479 mm3, p<0.001). Men experienced a significantly higher mortality rate (24.4% vs. 17%, p=0.001), but the death event tended to occur earlier in women (15±7 vs. 8±7 days, p= 0.07). Non-survivors had a higher coronary, thoracic aorta, and aortic valve calcium score. Female sex, a known independent predictor of a favorable outcome in SARS-CoV2 infection, was not protective in women with a coronary calcification volume greater than 100 mm3. There were significant differences in cardiovascular comorbidities and vascular calcifications between men and women with SARS-CoV2 pneumonia. The differences in outcomes can be at least partially explained by the different cardiovascular profiles. However, women with poor outcomes had the same coronary calcific burden as men. The presumed favorable female sex bias in COVID-19 must therefore be reviewed in the context of comorbidities, especially cardiovascular ones.

Impact of clinical and subclinical coronary artery disease as assessed by coronary artery calcium in COVID-19.

BACKGROUND AND AIMS: The potential impact of coronary atherosclerosis, as detected by coronary artery calcium, on clinical outcomes in COVID-19 patients remains unsettled. We aimed to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by coronary artery calcium score (CAC), in a large, unselected population of hospitalized COVID-19 patients undergoing non-gated chest computed tomography (CT) for clinical practice. METHODS: SARS-CoV 2 positive patients from the multicenter (16 Italian hospitals), retrospective observational SCORE COVID-19 (calcium score for COVID-19 Risk Evaluation) registry were stratified in three groups: (a) "clinical CAD" (prior revascularization history), (b) "subclinical CAD" (CAC >0), (c) "No CAD" (CAC = 0). Primary endpoint was in-hospital mortality and the secondary endpoint was a composite of myocardial infarction and cerebrovascular accident (MI/CVA). RESULTS: Amongst 1625 patients (male 67.2%, median age 69 [interquartile range 58-77] years), 31%, 57.8% and 11.1% had no, subclinical and clinical CAD, respectively. Increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p < 0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p < 0.001) were observed for patients with no CAD vs. subclinical CAD vs clinical CAD, respectively. The association with in-hospital mortality was independent of in-study outcome predictors (age, peripheral artery disease, active cancer, hemoglobin, C-reactive protein, LDH, aerated lung volume): subclinical CAD vs. No CAD: adjusted hazard ratio (adj-HR) 2.86 (95% confidence interval [CI] 1.14-7.17, p=0.025); clinical CAD vs. No CAD: adj-HR 3.74 (95% CI 1.21-11.60, p=0.022). Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds≤100, 101-400 and > 400, respectively, p < 0.001). The adj-HR per 50 points increase in CAC score 1.007 (95%CI 1.001-1.013, p=0.016). Cardiovascular risk factors were not independent predictors of in-hospital mortality when CAD presence and extent were taken into account. CONCLUSIONS: The presence and extent of CAD are associated with in-hospital mortality and MI/CVA among hospitalized patients with COVID-19 disease and they appear to be a better prognostic gauge as compared to a clinical cardiovascular risk assessment.

Coronary and total thoracic calcium scores predict mortality and provides pathophysiologic insights in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 â€‹± â€‹570.92 vs 206.80 â€‹± â€‹424.13 â€‹mm2, p â€‹< â€‹0.001); Volume (487.79 â€‹± â€‹565.34 vs 207.77 â€‹± â€‹406.81, p â€‹< â€‹0.001)], aortic valve [Volume (322.45 â€‹± â€‹390.90 vs 98.27 â€‹± â€‹250.74 mm2, p â€‹< â€‹0.001; Agatston 337.38 â€‹± â€‹414.97 vs 111.70 â€‹± â€‹282.15, p â€‹< â€‹0.001)] and thoracic aorta [Volume (3786.71 â€‹± â€‹4225.57 vs 1487.63 â€‹± â€‹2973.19 mm2, p â€‹< â€‹0.001); Agatston (4688.82 â€‹± â€‹5363.72 vs 1834.90 â€‹± â€‹3761.25, p â€‹< â€‹0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046-1.637, p â€‹= â€‹0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200-3.251, p â€‹= â€‹0.007) resulted to be independent predictors of in-hospital mortality. CONCLUSION: Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk.

Impact of renin-angiotensin system inhibitors on mortality during the COVID Pandemic among STEMI patients undergoing mechanical reperfusion: Insight from an international STEMI registry.

BACKGROUND: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. METHODS: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. RESULTS: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51-0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33-0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084-0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. CONCLUSIONS: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival.

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.