BACKGROUND. Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Antiviral immune response is crucial to achieve pathogen clearance; however, in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS. We performed a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19 and correlated these data with clinical outcomes. RESULTS. Patients with COVID-19 showed decreased numbers of circulating T, B, and NK cells and exhibited a skewing of CD8⁺ T cells toward a terminally differentiated/senescent phenotype. In agreement, CD4⁺ T and CD8⁺ T, but also NK cells, displayed reduced antiviral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in patients with COVID-19, particularly in those who required intensive care. The latter group of patients also showed increased serum IL-6 levels that inversely correlated to the frequency of granzyme A–expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION. The association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore antiviral mechanisms. FUNDING. This study was supported by funds from the Department of Experimental and Clinical Medicine of University of Florence (the ex-60% fund and the “Excellence Departments 2018–2022 Project”) derived from Ministero dell’Istruzione, dell’Università e della Ricerca (Italy).

Clinical significance of lactate in acute cardiac patients

In patients with the novel coronavirus (COVID-19) infection, the echocardiographic assessment of the right ventricle (RV) represents a pivotal element in the understanding of current disease status and in monitoring disease progression. The present manuscript is aimed at specifically describing the echocardiographic assessment of the right ventricle, mainly focusing on the most useful parameters and the time of examination. The RV direct involvement happens quite often due to preferential lung tropism of COVID-19 infection, which is responsible for an interstitial pneumonia characterized also by pulmonary hypoxic vasoconstriction (and thus an RV afterload increase), often evolving in acute respiratory distress syndrome (ARDS). The indirect RV involvement may be due to the systemic inflammatory activation, caused by COVID-19, which may affect the overall cardiovascular system mainly by inducing an increase in troponin values and in the sympathetic tone and altering the volemic status (mainly by affecting renal function). Echocardiographic parameters, specifically focused on RV (dimensions and function) and pulmonary circulation (systolic pulmonary arterial pressures, RV wall thickness), are to be measured in a COVID-19 patient with respiratory failure and ARDS. They have been selected on the basis of their feasibility (that is easy to be measured, even in short time) and usefulness for clinical monitoring. It is advisable to measure the same parameters in the single patient (based also on the availability of valid acoustic windows) which are identified in the first examination and repeated in the following ones, to guarantee a reliable monitoring. Information gained from a clinically-guided echocardiographic assessment holds a clinical utility in the single patients when integrated with biohumoral data (indicating systemic activation), blood gas analysis (reflecting COVID-19-induced lung damage) and data on ongoing therapies (in primis ventilatory settings).

Background and objectives Little information is available on the relation between insulin resistance and acute myocardial infarction. Methods In 253 consecutive nondiabetic patients with ST elevation myocardial infarction (STEMI) submitted to percutaneous coronary intervention, we assessed the prevalence of insulin resistance by homeostatic model assessment (HOMA) index and its prognostic role in early and late mortality. Results Insulin resistance was detectable in 52.9% of patients. Anterior STEMI was more frequent in insulin-resistant patients (P = 0.040), who showed higher values of probrain natriuretic peptide (P = 0.010), creatinine (P < 0.001), creatinine phosphokinase and creatinine phosphokinase-MB (MB, isoenzyme present in the myocardium; P = 0.016 and P = 0.003, respectively). At backward stepwise logistic regression analysis, the following variables were independent predictors for intra-intensive cardiac care unit mortality: HOMA index [hazard ratio 1.40; 95% confidence interval (CI) 1.02–1.95; P = 0.049]; C-peptide (hazard ratio 3.14; 95% CI 1.40–24.80; P = 0.001) and lactic acid (hazard ratio 2.50; 95% CI 1.41–4.44; P = 0.002). At long-term follow-up (Cox regression analysis), neither fasting glycaemia nor HOMA index resulted in predictors for mortality. Conclusion In nondiabetic STEMI patients submitted to percutaneous coronary intervention, insulin resistance, as assessed by HOMA index, is quite common and helps in the early prognostic stratification, as it represents an independent predictor of in-hospital mortality.

Guidelines stated that extracorporeal membrane oxygenation (ECMO) may improve outcomes after refractory cardiac arrest (CA) in cases of cardiogenic shock and witnessed arrest, where there is an underlying circulatory disease amenable to immediate corrective intervention. Due to the lack of randomized trials, available data are supported by small series and observational studies, being therefore characterized by heterogeneity and controversial results. In clinical practice, using ECMO involves quite a challenging medical decision in a setting where the patient is extremely vulnerable and completely dependent on the medical team’s judgment. The present review focuses on examining existing evidence concerning inclusion and exclusion criteria, and outcomes (in-hospital and long-term mortality rates and neurological recovery) in studies performed in patients with refractory CA treated with ECMO. Discrepancies can be related to heterogeneity in study population, to differences in local health system organization in respect of the management of patients with CA, as well as to the fact that most investigations are retrospective. In the real world, patient selection occurs individually within each center based on their previous experience and expertise with a specific patient population and disease spectrum. Available evidence strongly suggests that in CA patients, ECMO is a highly costly intervention and optimal utilization requires a dedicated local health-care organization and expertise in the field (both for the technical implementation of the device and for the intensive care management of these patients). A careful selection of patients guarantees optimal utilization of resources and a better outcome.