EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19. METHODS: SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions. RESULTS: EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha. CONCLUSION: EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.

Infection Complications after Lymphodepletion and Dosing of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or B Cell Non-Hodgkin Lymphoma.

Chimeric antigen receptor T (CAR-T) cell therapy has proven to be very effective in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). However, infections-related either due to lymphodepletion or the CAR-T cell therapy itself-can result in severe and potentially life-threatening complications, while side effects such as cytokine release syndrome (CRS) might complicate differential diagnosis. Sixty-seven dosings of CAR-T cells in sixty adult patients with NHL (85%) and ALL (15%) receiving CAR-T cell therapy were assessed for infectious complications. Almost two-thirds of patients (61%) developed fever following lymphodepletion and CAR-T cell dosing. Microbiological or radiological findings were observed in 25% of all cases (bacterial 12%, viral 5%, fungal 8%). Inpatient infections were associated with more lines of therapy and more severe CRS. However, overall serious complications were rare after CAR-T therapy, with one patient dying of infection. Pathogen detection after inpatient stay was infrequent and mostly occurred in the first 90 days after dosing. Infections in CAR-T cell treated patents are common. Fast and suitable identification and treatment are crucial in these heavily pretreated and immunocompromised patients. In most cases infectious complications are manageable. Nonetheless, standardized anti-infective prophylaxis and supportive therapy are mandatory to reduce morbidity and mortality in CAR-T cell therapy.

Analysis of Symptoms of COVID-19 Positive Patients and Potential Effects on Initial Assessment.

BACKGROUND: SARS-CoV-2 is a highly contagious virus, significantly impacting Germany among other countries since its emergence. Because of heterogeneous symptoms and a subset of patients even being asymptomatic at presentation, fast identification of infected patients remains challenging. OBJECTIVE: The goal of this study is the evaluation of different patient groups with a focus on symptoms and pre-existing illness at admission, as this is important for initial assessment and adequate emergency care. METHODS: COVID-19 positive patients at the University Hospital Heidelberg were retrospectively analyzed for disease history and symptoms at the initial presentation as well as mortality. The authors obtained institutional review board (IRB) approval by the Ethics Committee (Medical Faculty of Heidelberg University) prior to commencing the study. RESULTS: Dyspnea was more common in patients admitted to intermediate care/intensive care units (48 vs 13%, P<0.001) and showed a significantly higher percentage in the deceased (91 vs 48%, P=0.004). The symptoms of all presenting patients were highly variable, and many manifestations commonly associated with COVID-19 like cough, fever, and sore throat were only detected in a subset of patients, 60%, 43%, and 33%, respectively. CONCLUSION: Dyspnea was present significantly more often in patients dying of COVID-19 compared to all patients admitted to the IMC/ICU, necessitating adequate observation and monitoring. In all presenting patients, initial symptoms showed large variation; therefore, COVID should be considered as a main differential diagnosis at every patient presentation, and patients with high pre-test probability should, if possible, be isolated until testing results are known.