With the dramatic increase of confirmed cases of coronavirus disease (COVID-19) and the increasing death toll in China, timely and effective management of severely and critically ill patients appears to be particularly important. Previous studies on COVID-19 mainly described the general features of patients (1). However, little attention has been paid to clinical characteristics and outcomes of intensive care patients, data on whom are scarce but are of paramount importance to reduce mortality. Some of the results of these studies have been previously reported in the form of an abstract (2). Methods This study enrolled 344 severely and critically ill patients (intensive care patients) who were diagnosed with COVID-19 according to World Health Organization interim guidance by positive result of an RT-PCR assay of nasal and/or throat-swab specimens, and were hospitalized in eight intensive care wards (totaling approximately 330 beds) in Tongji hospital from January 25, 2020, through February 25, 2020. The intensive care wards staff intensivists and specialist nurses in intensive care and were equipped with continuous vital signs monitoring and respiratory support, including noninvasive and invasive ventilators, high-flow nasal cannula (HFNC) oxygen therapy, and extracorporeal membrane oxygenation. We collected demographic, clinical, laboratory, and radiologic findings, and treatment and outcome data from electronic medical records. The illness severity of COVID-19 was defined according to the Chinese management guideline for COVID-19 (version 6.0) (3). Cytokines were measured by a chemiluminescent immunometric assay (Immulite 1000; Diagnostic Products). Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin definition, and septic shock was defined according to the 2016 Third International Consensus definition (4, 5). Disseminated intravascular coagulation was

The alloimmune response against fully MHC-mismatched allografts, compared with immune responses to nominal antigens, entails an unusually large clonal size of alloreactive T cells. Thus, induction of peripheral allograft tolerance established in the absence of immune system ablation and reconstitution is a challenging task in transplantation. Here, we determined whether a reduction in the mass of alloreactive T cells due to apoptosis is an essential initial step for induction of stable allograft tolerance with non-lymphoablative therapy. Blocking both CD28-B7 and CD40-CD40 ligand interactions (co-stimulation blockade) inhibited proliferation of alloreactive T cells in vivo while allowing cell cycle-dependent T-cell apoptosis of proliferating T cells, with permanent engraftment of cardiac allografts but not skin allografts. Treatment with rapamycin plus co-stimulation blockade resulted in massive apoptosis of alloreactive T cells and produced stable skin allograft tolerance, a very stringent test of allograft tolerance. In contrast, treatment with cyclosporine A and co-stimulation blockade abolished T-cell proliferation and apoptosis, as well as the induction of stable allograft tolerance. Our data indicate that induction of T-cell apoptosis and peripheral allograft tolerance is prevented by blocking both signal 1 and signal 2 of T-cell activation.

Keeping drugs under control: Hydrothermally stable, hollow mesoporous silica spheres have a high drug storage capacity, and polyelectrolyte multilayers coated on the spheres act as a switch for drug release which is controlled by the pH or ionic strength of the release medium. The picture shows the release of ibuprofen (IBU) from spheres with and without coatings of sodium polystyrene sulfonate (PSS) and poly(allylamine hydrochloride) (PAH).