Role of comorbidities on the mortality in patients with SARS-CoV-2 infection: an Italian cohort study.

BACKGROUND: Cardiovascular comorbidities are a common cause of death in COVID-19 and the aim of this study is to evaluate the effect of comorbidities on mortality in COVID-19 patients. METHODS: In this retrospective observational study we enrolled 1049 patients hospitalized with confirmed SARS-CoV-2 infection in a single Italian Center from 21 February to 20 March 2020 Evaluated risk factors (RFs) were: advanced age, gender, hypertension, diabetes, atrial fibrillation, hyperlipidemia, chronic kidney disease, thyroid disease, chronic obstructive pulmonary disease, malignancy, stroke, cardiovascular disease, and peripheral vascular disease. Endpoint of the study was death from any cause. A multivariate logistic regression model was built using covariates that showed as statistically significant at univariate regression analysis. RESULTS: Median age at presentation was 71.1 years (IQR: 59.1-80.5); 244 (72.2%) were males. Primary outcome occurred in 338 patients (32.2%). In decedents, median survival from Hospitalization was 6 (IQR: 3-10) days. 264 decedents had 1 RF, 120 had 2 RFs and 39 had ≥3 RFs. At multivariate logistic regression model, variables associated with primary outcome were: age class (64-69 years) (OR 3.03, CI 1.75-5.31, p<0.001), age class (70-88 years) (OR 10.08, CI 6.67-15.72, p<0.001), age class (≥ 88 years) (OR 23.99, CI 13.21-44.82, p<0.001), male gender (OR 1.88, CI 1.36-2.62, p<0.001), diabetes (OR 1.56, CI 1.07-2.26, p=0.02), stroke (OR 3.41, CI 1.33-9.91, p=0.015). CONCLUSIONS: Age, male gender, presence of diabetes and stroke appeared as independent predictors of mortality in COVID-19 patients. A table for risk of 30 days-mortality in SARS-CoV-2 infection was built, based on odds ratios derived from multivariate regression analysis.

Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19.

BACKGROUND: Platelet activation and thrombotic events characterizes COVID-19. OBJECTIVES: To characterize platelet activation and determine if SARS-CoV-2 induces platelet activation. PATIENTS/METHODS: We investigated platelet activation in 119 COVID-19 patients at admission in a university hospital in Milan, Italy, between March 18 and May 5, 2020. Sixty-nine subjects (36 healthy donors, 26 patients with coronary artery disease, coronary artery disease, and seven patients with sepsis) served as controls. RESULTS: COVID-19 patients had activated platelets, as assessed by the expression and distribution of HMGB1 and von Willebrand factor, and by the accumulation of platelet-derived (plt) extracellular vesicles (EVs) and HMGB1+ plt-EVs in the plasma. P-selectin upregulation was not detectable on the platelet surface in a fraction of patients (55%) and the concentration of soluble P-selectin in the plasma was conversely increased. The plasma concentration of HMGB1+ plt-EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a 6-point ordinal scale (from 1 = discharged to 6 = death). Platelets interacting in vitro with SARS-CoV-2 underwent activation, which was replicated using SARS-CoV-2 pseudo-viral particles and purified recombinant SARS-CoV-2 spike protein S1 subunits. Human platelets express CD147, a putative coreceptor for SARS-CoV-2, and Spike-dependent platelet activation, aggregation and granule release, release of soluble P-selectin and HMGB1+ plt-EVs abated in the presence of anti-CD147 antibodies. CONCLUSIONS: Hence, an early and intense platelet activation, which is reproduced by stimulating platelets in vitro with SARS-CoV-2, characterizes COVID-19 and could contribute to the inflammatory and hemostatic manifestations of the disease.

Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) exhibit high thrombotic risk. The evidence on a potential independent prognostic role of antiplatelet treatment in those patients is limited. The aim of the study was to evaluate the prognostic impact of pre-admission low-dose acetylsalicylic acid (ASA) in a wide series of hospitalized patients with COVID-19. METHODS: This cohort study included 984 COVID-19 patients stratified according to ASA intake before hospitalization: ASA+ (n = 253) and ASA- (n = 731). Patients were included in ASA+ group if they received it daily in the 7 days before admission. 213 (83%) were on ASA 100 mg daily. Primary endpoint was a composite of in-hospital death and/or need for respiratory support upgrade, secondary endpoints were in-hospital death and need for respiratory support upgrade. RESULTS: Mean age was 72 [62; 81] with 69% of male patients. ASA+ patients were significantly older, with higher prevalence of comorbidities. No significant differences regarding the degree of respiratory dysfunction were observed. At 30-day Kaplan-Meier analysis, ASA+ patients had higher survival free from the primary endpoint and need for respiratory support upgrade, conversely in-hospital death did not significantly differ between groups. At multivariate analysis ASA intake was independently associated with a lower probability of reaching primary endpoint (HR 0.697, 95% C.I. 0.525-0.924; p = 0.012). CONCLUSIONS: In COVID-19 patients undergoing hospitalization, pre-admission treatment with ASA is associated with better in-hospital outcome, mainly driven by less respiratory support upgrade.

Antithrombotic therapy in patients with COVID-19? -Rationale and Evidence.

In patients with severe or critical Coronavirus disease 2019 (COVID-19) manifestations, a thromboinflammatory syndrome, with diffuse microvascular thrombosis, is increasingly evident as the final step of pro-inflammatory cytokines storm. Actually, no proven effective therapies for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exist. Preliminary observations on anticoagulant therapy appear to be associated with better outcomes in moderate and severe COVID-19 patients with signs of coagulopathy and in those requiring mechanical ventilation. The pathophysiology underlying the prothrombotic state elicited by SARS-CoV-2 outlines possible protective mechanisms of antithrombotic therapy (in primis anticoagulants) for this viral illness. The indications for antiplatelet/anticoagulant use (prevention, prophylaxis, therapy) are guided by the clinical context and the COVID-19 severity. We provide a practical approach on antithrombotic therapy management for COVID-19 patients from a multidisciplinary point of view.