Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19 (preprint)

A bstract Purpose Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. Methods We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. Results Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p=0.001), fasting blood glucose (HR 4.32, p<0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p=0.01) or fasting blood glucose ≥ 7 mmol/l (HR 3.07, p=0.015). Conclusions Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.

The Effect of Angiotensin II Infusion on Markers of Organ Function in Invasively Ventilated COVID-19 Patients (preprint)

Background: The use of angiotensin II (ANGII) in invasively ventilated COVID-19 patients is controversial. Its effect on markers of organ function is unknown.Methods: We used ANGII either as rescue vasopressor agent or as low dose vasopressor support. Patients treated before ANGII availability or in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of ANG on markers of organ function.Results: We compared 46 ANGII patients with 53 controls. Compared with controls, ANGII increased MAP (median difference, 9.05 mmHg [95% confidence interval, 1.87 to 16.22]; p = 0.013) and PaO2/FiO2 ratio (median difference, 23.17 [95% confidence interval, 3.46 to 42.88]; p = 0.021). ANGII had no effect on lactate, urinary output, serum creatinine, C-Reactive protein, platelet count, or thromboembolic complications. However, it significantly decreased the odd ratio of liver dysfunction (odds ratio: 0.32; 0.09 to 0.94) and, on Bayesian modelling, in patients with abnormal baseline serum creatinine, ANGII carried a 95.7% probability of decreasing renal replacement therapy use. Conclusions: In ventilated COVID-19 patients, ANGII therapy was associated with increased blood pressure and PaO2/FiO2 ratios, decreased odds ratio of liver dysfunction, and a high probability of decreasing renal replacement therapy use in patients with abnormal baseline serum creatinine. 

Viral Clearance After Early Corticosteroid Treatment In Patients With Moderate Or Severe Covid-19 (preprint)

The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients.Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs.The primary outcome was the time to nasopharyngeal swab negativization.A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization.Of 280 patients included, 59 (21.1%) patients were treated with steroids.Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p=0.023) or ≤100 mmHg (16.9% vs 12.7%; p=0.027), and length of hospitalization (20 vs 14 days; p<0.001).Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p=0.985).According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 >200 mmHg, and a lymphocyte count at admission >1.0*109/L. SARS-CoV-2 clearance was not associated with corticosteroid use.Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with early use of corticosteroids

Multifocal transient cortical brain lesions: a consistent MRI finding in neuro-COVID-19 patients (preprint)

We report four cases of subacute encephalopathy occurring in patients with SARS-CoV-2 infection. All patients have been intubated in the first week from onset of ARDS and presented neurological signs of agitation and spatial disorientation after weaning from mechanical ventilation. The MRI picture and the clinical features are described. MRI lesions characteristics are unusual but demonstrate a highly consistent pattern through all the four patients with similar neurological symptoms. They do not fulfill any typical criteria for a definite neuroradiological entity. Their predominantly parieto-occipital distribution recalls posterior reversible encephalopathy syndrome (PRES), although the prevalent cortical involvement and diffusion MRI pattern are not typical of PRES. We speculate that this pattern may be related to a possible transient dysregulation of vasomotor reactivity.