Dysregulated early transcriptional signatures linked to mast cell and interferon responses are implicated in COVID-19 severity.

Background: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are thought to underlie the progression of coronavirus disease 2019 (COVID-19) to severe disease. We sought to determine whether early host immune-related gene expression could predict clinical progression to severe disease. Methods: We analysed the expression of 579 immunological genes in peripheral blood mononuclear cells taken early after symptom onset using the NanoString nCounter and compared SARS-CoV-2 negative controls with SARS-CoV-2 positive subjects with mild (SARS+ Mild) and Moderate/Severe disease to evaluate disease outcomes. Biobanked plasma samples were also assessed for type I (IFN-α2a and IFN-ß), type II (IFN-γ) and type III (IFN-λ1) interferons (IFNs) as well as 10 additional cytokines using multiplex immunoassays. Results: We identified 19 significantly deregulated genes in 62 SARS-CoV-2 positive subject samples within 5 days of symptom onset and 58 SARS-CoV-2 negative controls and found that type I interferon (IFN) signalling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1) and genes encoding proinflammatory cytokines (TNF, TNFSF4, PTGS2 and IL1B) were upregulated in both SARS+ groups. Moreover, we found that FCER1, involved in mast cell activation, was upregulated in the SARS+ Mild group but significantly downregulated in the SARS+ Moderate/Severe group. In both SARS+ groups we discovered elevated interferon type I IFN-α2a, type II IFN and type III IFN λ1 plasma levels together with higher IL-10 and IL-6. These results indicate that those with moderate or severe disease are characterised by deficiencies in a mast cell response together with IFN hyper-responsiveness, suggesting that early host antiviral immune responses could be a cause and not a consequence of severe COVID-19. Conclusions: This study suggests that early host immune responses linking defects in mast cell activation with host interferon responses correlates with more severe outcomes in COVID-19. Further characterisation of this pathway could help inform better treatment for vulnerable individuals.

Lactate dehydrogenase and aspartate aminotransferase levels associated with the severity of COVID­19: A systematic review and meta­analysis.

Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) are important indicators of cardiovascular, muscle and liver lesions, and can be used as prognostic indicators for infectious diseases, such as coronavirus disease 2019 (COVID-19). The present systematic review and meta-analysis assessed the prognostic value of LDH and AST levels for COVID-19 severity. Ovid-Medline, PubMed, Embase and The Cochrane Library were used to search for articles, according to the inclusion and exclusion criteria, until July 2022. The meta-analysis was performed using Revman5.3 and Stata15.1. Standardized mean difference (SMD) and 95% confidence intervals (CIs) of LDH and AST concentrations were analyzed using a random-effects model. Heterogeneity was investigated using meta-regression and subgroup methods. A total of 4,342 patients with COVID-19 in 23 articles were included in the present study. LDH (SMD=1.21; 95% CI: 0.98, 1.44) and AST (SMD=0.68; 95% CI: 0.54, 0.81) were significantly higher in patients with severe COVID-19 compared with in those with non-severe COVID-19. Serum LDH and AST levels in critically ill patients with COVID-19 were increased, suggesting a correlation between the levels of LDH and AST and the severity of COVID-19. These findings may help to develop a risk-stratified approach to the care of patients with this disease.

Correlation of the level of plasma biomarkers with acute graft-versus-host disease in children.

BACKGROUND: Acute graft-versus-host disease is one of the major complications of allogeneic hematopoietic stem cell transplantation, and it is also the key to the success of transplantation, which is particularly important to find specific biomarkers of acute graft-versus-host disease for the early diagnosis and treatment. The immune function of children is imperfect, and the changes of plasma biomarkers after acute graft-versus-host disease have their own characteristics. OBJECTIVE: To explore the correlation of plasma levels of soluble growth stimulation expressed gene 2 (sST2), regenerating islet-derived protein 3 alpha (REG3α), tumor necrosis factor receptor 1 (TNFR1), interleukin 6 (IL6), and interleukin 8 (IL8) with acute graft-versus-host disease in children after allogeneic hematopoietic stem cell transplantation. It is expected to provide reliable detection biomarkers for early diagnosis of acute graft-versus-host disease and prediction of therapy effect and prognosis. METHODS: Samples were collected from 127 pediatric patients who underwent allogeneic hematopoietic stem cell transplantation from March 2019 to December 2020 in the Department of Pediatrics, Nanfang Hospital. The plasma was collected at multiple time points, including 10 days before transplantation, 0, 7, 14, 28, and 90 days after transplantation, at the onset of acute graft-versus-host disease symptoms, 1, 2, and 4 weeks after acute graft-versus-host disease therapy. The plasma concentrations of sST2, REG3α, TNFR1, IL6 and IL8 were detected by the Luminex technology. RESULTS AND CONCLUSION: (1) Plasma samples were collected from 100 of 127 patients at the point of occurrence of acute graft-versus-host disease. Sixty cases never developed acute graft-versus-host disease symptoms;40 cases presented acute graft-versus-host disease, among which 9 cases developed II-IV gastrointestinal acute graft-versus-host disease according to EBMT-NIH-CIBMTR classification standard. (2) The plasma concentrations of sST2 and REG3α at onset point in patients were significantly higher in the acute graft-versus-host disease group compared with the non-acute graft-versus-host disease group (P < 0.05). sST2 was significantly increased at 7 days after transplantation in the acute graft-versus-host disease group than that in the non-acute graft-versus-host disease group (P < 0.05). The sST2 and REG3α levels were significantly higher in the II-IV gastrointestinal acute graft-versus-host disease group than those in the non-gastrointestinal acute graft-versus-host disease group (P < 0.01;P < 0.05). There were no significant differences in TNFR1, IL6 and IL8 levels at onset point and 7 days after transplantation in patients between the acute graft-versus-host disease group and the non-acute graft-versus-host disease group (P > 0.05). (3) In all acute graft-versus-host disease patients, the plasma concentrations of sST2 and REG3α in the steroid-resistant acute graft-versus-host disease group showed increasing tendency compared with steroid-sensitive acute graft-versus-host disease group. (4) It is concluded that the increate of plasma sST2 and REG3α levels at onset point after transplantation suggests the incidence of acute graft-versus-host disease. sST2 and REG3α in plasma can be helpful for the early prediction of acute graft-versus-host disease. By analyzing the levels of biomarkers at 1, 2, and 4 weeks after treatment, no decrease in the sST2 and REG3α levels in patients with acute graft-versus-host disease after treatment may be related to poor prognosis. (English) [ FROM AUTHOR] 背景：急性移植物抗宿主病是造血干细胞移植最主要的并发症之一，也是影响移植成败的关键，寻找其特异性生物学标记物对于疾病的早 期诊断及治疗尤为重要。婴幼儿时期免疫功能不完善，其急性移植物抗宿主病发生后血浆生物标记物的变化有其自身特点。 目的：研究异基因造血干细胞移植儿童患者血浆可溶性生长刺激表达基因2、胰岛再生衍生因子3α、肿瘤坏死因子受体1、白细胞介素6 和白细胞介素8水平变化与急性移植物抗宿主病的关系，以期为急性移植物抗宿主病的早期诊断、预测治疗效果和预后提供可靠的检测指 标。 方法：南方医院儿科2019年3月至2020 年12月行异基因造血干细胞移植共计127例患儿，采集移植前10 d、移植后第0，7，14，28，90 天、临床急性移植物抗宿主病症状出现时、急性移植物抗宿主病药物干预后1，2，4周患儿外周血，采用Luminex方法检测血清可溶性生长 刺激表达基因2、胰岛再生衍生因子3α、肿瘤坏死因子受体1、白细胞介素6和白细胞介素8水平。 结果与结论：①在127例患儿中有100例在急性移植物抗宿主病发生点采集血浆标本，按照EBMT-NIH-CIBMTR 分级标准未发生急性移植物抗 宿主病60例，发生急性移植物抗宿主病有40例，其中有9例Ⅱ-Ⅳ度肠道急性移植物抗宿主病。②急性移植物抗宿主病组发生点的血浆可 溶性生长刺激表达基因2和胰岛再生衍生因子3α水平高于无急性移植物抗宿主病组，差异均有显著性意义(P < 0.05)。与无急性移植物抗宿 主病组相比，急性移植物抗宿主病组移植后7 d的血浆可溶性生长刺激表达基因2水平显著增加(P < 0.05)。单纯Ⅱ-Ⅳ度肠道急性移植物抗 宿主病组发生点的血浆可溶性生长刺激表达基因2和胰岛再生衍生因子3α水平高于非肠道急性移植物抗宿主病组，差异均有显著性意义(P< 0.01；P < 0.05)。在发生点和造血干细胞移植后7 d时，急性移植物抗宿主病组和非急性移植物抗宿主病组间肿瘤坏死因子受体1、白细胞 介素6和白细胞介素8水平无显著差异(P > 0.05)。③在所有急性移植物抗宿主病患者中，与激素敏感组相比，激素耐药组的血浆可溶性生长 刺激表达基因2和胰岛再生衍生因子3α水平呈上升趋势。④结果表明，移植后发生点的血浆可溶性生长刺激表达基因2和胰岛再生衍生因 子3α水平升高提示急性移植物抗宿主病的发生，二者有助于急性移植物抗宿主病的早期预测。通过分析用药后1，2，4周的生物标记物水 平，急性移植物抗宿主病患者治疗后血浆可溶性生长刺激表达基因2和胰岛再生衍生因子3α水平不降低可能与预后不良相关。 (Chinese) [ FROM AUTHOR] Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo zu zhi gong cheng yan jiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Do Anxiety and Depression Levels Affect the Inflammation Response in Patients Hospitalized for COVID-19.

OBJECTIVE: The whole world is still struggling with the COVID-19 pandemic. Inflammation response, thought to be associated with severe illness and death, is an important research topic in COVID-19. Inflammation is also an essential condition explored in psychiatric illnesses. Our knowledge about the relationship between the inflammation response and psychiatric comorbidities in patients with COVID-19 is very limited. In this study, the relationship between anxiety and depression levels and inflammation response of patients with COVID-19 hospitalized in the hospital was examined. METHODS: 175 patients were included in the study. Sociodemographic Data Form, Beck Depression Inventory and Beck Anxiety Inventory were applied to the patients. To evaluate the inflammation responses, blood sedimentation rate, C-reactive protein (CRP), procalcitonin, ferritin, neutrophil/lymphocyte ratio (NLR), and IL-6 levels were examined. RESULTS: In our study, no relationship was found between anxiety and depression levels and inflammatory responses in patients hospitalized with a diagnosis of COVID-19. Anxiety and depression levels of women were higher than men, and NLR, ferritin, IL-6 levels were found to be lower than men. Anxiety levels increase with age. There is a positive correlation between NLR and ferritin levels and duration of hospitalization. CONCLUSION: Our study examining the relationship of psychiatric comorbidities with the inflammation response and our increasing literature knowledge, together with studies evaluating the mental effects of COVID-19, suggest that determining the relationship between inflammation responses and psychiatric comorbidities in COVID-19, whose pathophysiology has not been clarified yet, maybe an essential step in interventions on the course of the disease.