Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ∼200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.

Crystal Structure and Electrochemical Properties of AB3.8-Type Earth Mg Ni-Based Hydrogen Storage Alloys

La0.8-xPrxMg0.2Ni3.8 (x=0,0.15,0.3,0.4) alloys were prepared by induction melting followed by annealing treatment at 1173K for 24 h. Alloys structure and electrochemical properties of different Pr elecment have been studied systematically by X-ray diffraction(XRD) with the Rietveld methold , scanning electron microscope (SEM)and electrochemical experiments. Alloys structure analyses show that all of the alloys mainly consisted of complex phases such as (La,Pr,Mg)5Ni19 phase(Ce5Co19-type,SG:R-3m), (La,Pr,Mg)5Ni19 phase (Pr5Co19-type, SG:P63/mmc)and (La,Pr)Ni5 phase(CaCu5-type,SG:P6/mmm), Pr eletment was benefited to the formation of Pr5Co19-type phase, The (La,Pr,Mg)5Ni19 phase not only exists in high temperature area but also exists in low temperature area.The activation characteristic and maximum discharge capacity got worse with increasing Pr content,At the same time, The Pr5Co19–type phase and Ce5Co19–type phase all had better electrochemical cyclic stability than the PuNi3-type phase in earth–Mg–Ni-based Hydrogen Storage Alloys.The cyclic stability of alloy electrodes was a closely related to the stacking structures consisting of one Laves-type slab (AB2) and three CaCu5-type slabs (AB5) along the c-axis.

Performance of Heat Driven Type Water Cooler Using Metal Hydride

In this study, we aim at developing the heat driven type water cooler using metal hydride (abbr., MH) alloy. Heat driven type MH water cooler is one of the chemical heat pumps, and the endothermic reaction on the cooling part MH (to put it simply, MH2) is used for the cooling. Because MH is too expensive (200∼300 $ per 1kg) and has an unfavorable activation characteristic, this cooler has not been used generally yet. In order to increase the system performance, we use a new TiFe alloy, which has been developed by co-researcher, to the heat source part MH (to put it simply, MH1). Moreover, to improve the cooling load per MH mass, we mix the brush type carbon fiber, 2 mass% into MH beds. By this method, the cooling load per MH mass is been increased to 0.078 kW/kg (MH2).

Ex Vivo Cultured Megakaryocytes Express Functional Glycoprotein IIb-IIIa Receptors and Are Capable of Adenovirus-Mediated Transgene Expression

Investigation of the molecular basis of megakaryocyte (MK) and platelet biology has been limited by an inadequate source of genetically manipulable cells exhibiting physiologic MK and platelet functions. We hypothesized that ex vivo cultured MKs would exhibit agonist inducible glycoprotein (GP) IIb-IIIa activation characteristic of blood platelets and that these cultured MKs would be capable of transgene expression. Microscopic and flow cytometric analyses confirmed that human hematopoietic stem cells cultured in the presence of pegylated recombinant human MK growth and development factor (PEG-rHuMGDF) differentiated into morphologic and phenotypic MKs over 2 weeks. Cultured MKs expressed functional GPIIb-IIIa receptors as assessed by agonist inducible soluble fibrinogen and PAC1 binding. The specificity and kinetics of fibrinogen binding to MK GPIIb-IIIa receptors were similar to those described for blood platelets. The reversibility and internalization of ligands bound to MK GPIIb-IIIa also shared similarities with those observed in platelets. Cultured MKs were transduced with an adenoviral vector encoding green fluorescence protein (GFP) or β-galactosidase (β-gal). Efficiency of gene transfer increased with increasing multiplicities of infection and incubation time, with 45% of MKs expressing GFP 72 hours after viral infection. Transduced MKs remained capable of agonist induced GPIIb-IIIa activation. Thus, ex vivo cultured MKs (1) express agonist responsive GPIIb-IIIa receptors, (2) are capable of expressing transgenes, and (3) may prove useful for investigation of the molecular basis of MK differentiation and GPIIb-IIIa function.

Ex Vivo Cultured Megakaryocytes Express Functional Glycoprotein IIb-IIIa Receptors and Are Capable of Adenovirus-Mediated Transgene Expression

Investigation of the molecular basis of megakaryocyte (MK) and platelet biology has been limited by an inadequate source of genetically manipulable cells exhibiting physiologic MK and platelet functions. We hypothesized that ex vivo cultured MKs would exhibit agonist inducible glycoprotein (GP) IIb-IIIa activation characteristic of blood platelets and that these cultured MKs would be capable of transgene expression. Microscopic and flow cytometric analyses confirmed that human hematopoietic stem cells cultured in the presence of pegylated recombinant human MK growth and development factor (PEG-rHuMGDF) differentiated into morphologic and phenotypic MKs over 2 weeks. Cultured MKs expressed functional GPIIb-IIIa receptors as assessed by agonist inducible soluble fibrinogen and PAC1 binding. The specificity and kinetics of fibrinogen binding to MK GPIIb-IIIa receptors were similar to those described for blood platelets. The reversibility and internalization of ligands bound to MK GPIIb-IIIa also shared similarities with those observed in platelets. Cultured MKs were transduced with an adenoviral vector encoding green fluorescence protein (GFP) or β-galactosidase (β-gal). Efficiency of gene transfer increased with increasing multiplicities of infection and incubation time, with 45% of MKs expressing GFP 72 hours after viral infection. Transduced MKs remained capable of agonist induced GPIIb-IIIa activation. Thus, ex vivo cultured MKs (1) express agonist responsive GPIIb-IIIa receptors, (2) are capable of expressing transgenes, and (3) may prove useful for investigation of the molecular basis of MK differentiation and GPIIb-IIIa function.

Serum Biopterin as a Marker of Immune Activation in the Spontaneously Diabetic BB Rat

Summary Tetrahydrobiopterin (BH4), is a pteridine product which is released by rodent macrophages and fibroblasts upon activation by cytokines. It has previously been reported as a potentially useful marker for monitoring immune activation during the prediabetic prodrome in the spontaneously diabetic BB rat. We have used serial serum BH4 measurements, first to confirm the hypothesis that serum BH4 is elevated as a result of immunostimulation, and second to monitor more closely the serum BH4 levels during the prediabetic prodrome in a cohort of diabetes prone BB rats. A modified biopterin radioimmunoassay protocol was used to establish a reference range of 25.5-80.1 nmolll (95% confidence limits) for 70 Wistar rats of mean age six months. When eight adult Wistar rats were treated with sic BCG there was a significant increase in serum BH4 level (p<O.Ol) which returned to pre-treatment levels by day 16, coincident with the disappearance of visible signs of inflammation. A cohort of 26 diabetes prone BB rats, their diabetes resistant controls (n=20) and a cohort of Wistar controls (n=20) were then used to monitor serum BH4 levels from 30-120 days of age, at frequent intervals. The diabetes incidence in the diabetes prone animals was 100% with a mean age of onset of 80 days. The serum tetrahydrobiopterin level was significantly higher at day 30 in all three groups (p< 0.05) than at any other time point. The serum BH4 level in the diabetes prone group was significantly higher at day 30 (p<O.Ol ) and day 60 (p<0.05) than in either control group. These results show that serum BH4 is a sensitive marker for immune activation following subcubaneous injection of BCG in the rat, and is detectable using RIA. Serum BH4 was maximum in this study at day 30, but the significantly higher levels at days 30 and 60 in the diabetes prone compared with the diabetes resistant animals suggest that the immune activation characteristic of prediabetes can be detected biochemically in blood samples.