The Role of the IL-33/ST2 Axis in CpG-Induced Macrophage Activation Syndrome.

Background: Macrophage activation syndrome (MAS) is a fatal inflammatory condition, which is often associated with the elevation of multiple proinflammatory cytokines and multiple organ dysfunction. Previous studies have shown that ST2 contributes to T cell overactivation and plays a detrimental role in mouse models of primary hemophagocytic lymphohistiocytosis. The purpose of this study was to investigate the role of the IL-33/ST2 axis in a mouse model of MAS induced by repeated injections of cytosine-phosphate-guanine (CpG). Methods: Serum cytokines were determined using the cytometric bead array by flow cytometry. IL-33 and ST2 were detected by immunohistochemistry and real-time quantitative PCR in the liver and spleen of mice. CD3 and F4/80 in the liver were detected by immunohistochemistry. Inflammatory macrophages and effector memory T lymphocytes were detected by flow cytometry. Result: The CpG-induced MAS model was successfully induced after repeated CpG injections, presenting with hypercytokinemia and hepatosplenomegaly. The numbers of IL-33 positive cells in the liver and spleen decreased significantly, while the expression of ST2 in the liver tended to increase in the mice with MAS. IL-33 and St2 knockout mice showed similar levels of hepatosplenomegaly, peripheral blood count, and cytokine storm when compared with wild-type (WT) mice after induction of MAS. There were also no significant differences in liver pathology (including inflammatory cell infiltration of CD3 and F4/80) and levels of splenic inflammatory macrophages and effector memory T cells between the WT and knockout mice. Conclusion: These results suggested that IL-33 decreased in the liver and spleen tissues of MAS mice. Further results suggest that IL-33 and St2 knockout mice have no treatment potential in CpG-induced MAS. Thus, the IL-33/ST2 axis has little effect on the prognosis of CpG-induced MAS.

The Interaction of Apelin and FGFR1 Ameliorated the Kidney Fibrosis through Suppression of TGFß-Induced Endothelial-to-Mesenchymal Transition.

Both epithelial-to-mesenchymal (EMT) and endothelial-to-mesenchymal (EndMT) transitions have shown to contribute to the development and progression of kidney fibrosis. It has been reported that apelin, a regulatory peptide, alleviates EMT by inhibiting the transforming growth factor ß (TGFß) pathway in renal diseases. Additionally, fibroblast growth factor receptor 1 (FGFR1) has been shown to be a key inhibitor of EndMT through suppression of the TGFß/Smad pathway. In this study, we found that apelin and FGFR1 were spatially close to each other and that the apelin and FGFR1 complex displayed inhibitory effects on TGFß/Smad signaling as well as associated EndMT in diabetic kidney fibrosis. In cultured human dermal microvascular endothelial cells (HMVECs), we found that the anti-EndMT and anti-TGFß/Smad effects of apelin were dampened in FGFR1-deficient cells. Either siRNA- or an inhibitor-mediated deficiency of apelin induced the Smad3 phosphorylation and EndMT. Streptozotocin-induced CD-1 diabetic mice displayed EndMT and associated kidney fibrosis, which were restored by apelin treatment. The medium from apelin-deficient endothelial cells stimulated TGFß/Smad-dependent EMT in cultured HK2 cells. In addition, depletion of apelin and the FGFR1 complex impaired CEBPA expression, and TGFß-induced repression of CEBPA expression contributed to the initiation of EndMT in the endothelium. Collectively, these findings revealed that the interaction between apelin and FGFR1 displayed renoprotective potential through suppression of the TGFß/Smad/CEBPA-mediated EndMT/EMT pathways.

The aberrant levels of decorin induce damages of human salivary gland epithelial cells and polarization of macrophages.

OBJECTIVES: This study aimed to preliminarily address the levels of decorin (DCN, a critical component of extracellular matrix) and its potential roles in primary Sjögren's syndrome (pSS). METHODS: DCN levels were determined in the salivary glands of experimental SS (ESS) mice and pSS patients by RNA sequencing, bioinformatics analysis, or immunohistochemical staining. Its correlation with interested genes and co-localization with a putative receptor was studied in pSS patients. In addition, its potential roles on salivary gland epithelium and macrophages were tested by exogenous administration to corresponding cell lines, followed by the evaluation of apoptosis using flow cytometry or cytokine expression using quantitative real-time polymerase chain reaction. RESULTS: Our data revealed a significant elevation of DCN in the salivary glands of the ESS mice model and pSS patients. In addition, the bioinformatics analysis of DCN in the GSE40611 (RNA-seq, parotid glands) dataset displayed an elevation of the DCN level in the parotid glands of pSS patients that positively correlated with several chemokines (CXCL13, CXCL9, and CCL20), Interleukin -1 ß (IL1 -ß), and caspase3 but negatively correlated with the proliferation relative gene MKI67. The stimulatory effects of DCN on the salivary gland epithelial cells (A253 cell line) and macrophages have been determined as they are considered active participants in the progression of SS. The data showed that DCN induced the apoptosis of A253 cells and polarization of macrophages towards the M1 phenotype, characterized by the expression of pro-inflammatory cytokines. CONCLUSIONS: Our study provided preliminary evidence to understand the clinical significance of DCN in pSS and broadened our horizons in understanding the mechanism of pSS.

The landscape of T and B lymphocytes interaction and synergistic effects of Th1 and Th2 type response in the involved tissue of IgG4-RD revealed by single cell transcriptome analysis.

OBJECTIVES: To investigate the landscape of T-B cell interaction, immune receptor profiles and effects of different types of immune responses in the involved tissues of IgG4-RD. METHODS: Single cell RNA sequencing, bulk sample RNA sequencing, immune receptor repertoire analysis (both BCR and TCR), multi-color flow cytometry, and in-vitro assays with model cells (e.g. EBV-immortalized B cells from IgG4-RD patient) and histologic methods were applied to investigate the immunopathological features of IgG4-RD from multiple aspects. RESULTS: Ectopic germinal center formation was observed in IgG4-RD patients at advanced disease stage, and a large part of B cells in involved tissue were germinal center B cell-like. Germinal center reaction in IgG4-RD led to the irregularities of both TCR and BCR clones in the involved tissues, and limited clonal overlaps among different samples. Enhanced Th1- and Th2-type responses were observed in involved tissues of IgG4-RD and patients with both increased Th1- and Th2-type response related cell subsets possessed more severe inflammatory indices. Analyses to the origin of IGHG4 transcripts in IgG4-RD indicated that IgG4 could be switched from IgM directly, or from other IgG subclasses. In vitro assays with EBV-immortalized B cells, fibroblasts and epithelial cells revealed the effects of Th1-type and Th2-type responses on germinal center reaction, ectopic expression of MHC-II molecules, and formation of tertiary lymphoid structures. CONCLUSIONS: Synergistic effects of Th1- and Th2-type responses were involved in the pathogenesis of IgG4-RD via their influences on both acute inflammatory processes and the chronicity and complexity of IgG4-RD.

IL-33/ST2 axis contributes to the dermal fibrosis of systemic sclerosis via promoting fibroblasts activation.

BACKGROUND: Systemic sclerosis (SSc) is a chronic immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs. Interleukin-33 (IL-33) has been recently implicated in several autoimmune diseases through its receptor ST2. OBJECTIVE: The aim of this study was to investigate the role and underlying mechanism of IL-33/ST2 axis in the fibrotic disorder of SSc. METHODS: The bleomycin (BLM)-induced fibrotic skin and skin biopsies of SSc patients were used to detect the expression of IL-33 and ST2. Human dermal fibroblasts were stimulated with recombinant IL-33(rIL-33) protein and their activation, proliferation and migration were assessed. The role of IL-33/ST2 axis was investigated in mouse fibrosis model via histologically assessing skin fibrosis after IL-33 gene knockout. ST2 neutralizing antibody treatment was also obtained to estimate the possible effect. RESULTS: The number IL-33+ cells and ST2+ cells were increased in the lesion skin of SSc patients and BLM-induced mouse. Human skin fibroblasts highly expressed ST2 protein, and the proliferation, migration, and collagen expression were significantly elevated after rIL-33 stimulation, accompanied by the activation of MAPKs and NF-kB pathways. The severity of skin fibrosis was significantly reduced in il33-/- mice compared with WT mice. Blockade of IL-33 receptor using an anti-ST2 neutralizing antibody effectively ameliorated the skin fibrosis. CONCLUSION: These data indicate that IL-33/ST2 axis contributes to the fibrotic skin injury of SSc via promoting fibroblasts activation, and IL-33/ST2 blockade might serve as a novel strategy to inhibit the fibrosis progression in patients of SSc.

The IL-33/ST2 Axis Promotes Primary Sjögren's Syndrome by Enhancing Salivary Epithelial Cell Activation and Type 1 Immune Response.

The molecular mechanisms of primary Sjögren's syndrome (pSS) are poorly understood. In this study, we explored the role of the IL-33/ST2 axis in the development of pSS. In the mouse model of experimental Sjögren's syndrome, we found that the saliva flow rate at weeks 4 and 30 was preserved in IL-33-/- and ST2-/- mice, compared with that of wild-type mice. At week 30 of experimental Sjögren's syndrome induction, the histological score, anti-nuclear Ab levels, and numbers of Th1 and B cells in draining lymph nodes of the salivary gland were lower in the IL-33-/- and ST2-/- mice, whereas Th17 cells and regulatory T cells were not changed. Primary salivary gland epithelial cells expressed the IL-33 receptor ST2. After stimulation with rIL-33, salivary gland epithelial cells increased the transcriptional levels of CD86 and CCL2, accompanied by the activation of the NF-κB inflammatory pathway. There was a synergistic effect between rIL-33 and rIL-12 in augmenting the production of IFN-γ in CD4+ T cells. In the pSS patients, the expression of IL-33 was elevated in the labial salivary gland, with the number of IL-33+ cells positively correlated with the score of the EULAR (European Alliance of Associations for Rheumatology) Sjögren's syndrome disease activity index (ESSDAI). ST2 was highly expressed in the cytoplasm of ductal epithelial cells, with low levels of expression in lymphatic infiltration sites. Our data suggest that the IL-33/ST2 axis may promote the development of pSS by enhancing salivary epithelial cell activation and the type 1 immune response.

Validity and Longitudinal Invariance of the 10-Item Connor-Davidson Resilience Scale (CD-RISC-10) in Chinese Left-Behind and Non-Left-Behind Children.

The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is a self-report instrument widely used to assess resilience in particular demographics. This study aimed to evaluate the validity and measurement invariance (MI) of the CD-RISC-10 in Chinese left-behind children. A total of 968 children from three middle schools in Guizhou Province participated in this study, with the CD-RISC-10 used twice, at the base line time point and again after six months. The Ego-resilience Scale (ERS), and General Self-efficiency Scale (GSES-10) were also used as criteria-related validity instruments. Confirmatory factor analysis (CFA) was carried out to examine the one-factor model and the MI with regards to gender and left-behind status, as well as the longitudinal measurement invariance (LMI). The study proved satisfactory reliability and validity of the CD-RISC-10, with good criterion validity with the ERS and GSES-10. CFA results showed that the satisfactory model fit for the one-factor structure was supported in all groups (e.g., CFI = .942, TLI = .925, RMSEA = .057). The strict MI was evident across genders, as well as both the left-behind and non-left-behind groups. Additionally, the LMI of the CD-RISC-10 was also adequately supported. Generally speaking, these findings demonstrate that the CD-RISC-10 can effectively measure the resilience level of left-behind children - boys as well as girls - in China.

A Generalizability Analysis of the Meaning in Life Questionnaire for Chinese Adolescents.

The level of meaning in life not only affects the physical health of individuals, but also is closely related to their mental health. At present, many self-reported questionnaires are being used to measure the meaning in life of Chinese adolescents. Using the multivariate generalizability theory, this study investigated the psychometric properties and the internal structure of the Meaning in Life Questionnaires (MLQs), the most widely used questionnaire for assessing the level of meaning in life of Chinese adolescents. The data were sample of 1,951 junior high school students from Guizhou, China. Multivariate random measurement mode p × i° is the primary analytic approach. Results showed that the generalizability coefficient and dependability index of the scale were 0.86 and 0.85, respectively. The generalizability coefficients of presence of meaning and search for meaning were 0.76 and 0.85, respectively, and the dependability indexes were 0.75 and 0.85 for MLQ-P and MLQ-S, respectively. The design of each factor for MLQ is reasonable in terms of score ratio and the number of projects. In brief, the reliability and factor structure of the scale are satisfactory.

Factor Structure and Psychometric Properties for the PTSD Checklist of Chinese Adolescents in the Closed Period after the COVID-19 Outbreak.

After COVID-19 appeared in China in December 2019, the mental health of adolescents, as a vulnerable group in public health emergencies, was negatively affected by the epidemic and the unprecedented prevention and control measures. The purpose of this study was to investigate the factor structure and psychometric properties of the Posttraumatic Stress Disorder (PTSD) Checklist (PCL) among Chinese adolescents. A total of 915 participants completed the PTSD. Confirmatory factor analyses (CFAs) and multi-group CFAs were used to test the factor structure and psychometric properties of PTSD. The CFA results showed that five-factor PCL was the optimal fitting model with satisfactory reliability and validity; moreover, it was suggested that the properties of PCL were invariant across gender, PTSD and asymptomatic groups, early and late adolescents, as well as over time. In summary, PCL is applicable among Chinese adolescents and can be used for effective measurement of PTSD caused by epidemics and to conduct cross-group studies.

The Factor Structure and Rasch Analysis of the Fear of COVID-19 Scale (FCV-19S) Among Chinese Students.

The Fear of COVID-19 Scale (FCV-19S) is a new one-dimensional scale used to measure fear of an individual about the COVID-19. Given the seriousness of the COVID-19 situation in China when our study was taking place, our aim was to translate and examine the applicability of the FCV-19S in Chinese students. The sample used for validation comprised 2,445 Chinese students. The psychometrical characteristics of the Chinese FCV-19S (FCV-19S-C) were tested using Rasch analysis. Principal component analysis (PCA) proved the unidimensional structure of the model. Both infit and outfit mean square (MNSQ) values (0.69-1.31) and point-measure correlations (0.82-0.86) indicated a good model fit. Person-item separation and reliability values indicated good reliability of the scale. The person-item map revealed an acceptable level of match between the persons and the items. Differential item functioning of the FCV-19S-C showed no differences with respect to age or gender. FCV-19S-C scores were significantly associated with anxiety, stress, depression, ego-resilience, and general health. The FCV-19S-C was proven to be effective in measuring fear of Chinese students about the COVID-19.

The factor structure and psychometric properties of the Chinese version of the Positive and Negative Suicide Ideation Inventory (PANSI-C) in a non-clinical sample of Chinese adolescents.

BACKGROUNDS: The Positive and Negative Suicide Ideation (PANSI) Inventory is a widely used self-report questionnaire which is designed to comprehensively evaluate the protective factors and negative risk factors associated with suicidal behaviors among adolescents. The present study aimed to evaluate the psychometric properties and measurement invariance of the Chinese version of the PANSI in a non-clinical sample of Chinese adolescents. METHODS: Participants (N = 1198) were Chinese middle school students aged 11-17 years (44.8% boys and 51.9% girls, 3.3% missing values) in Guizhou Province. All participants completed the Chinese version of the Positive and Negative Suicide Ideation Inventory (PANSI-C), the Rosenberg self-esteem scale (RSE), and the suicide probability scale (SPS). Cronbach's alpha coefficients, confirmatory factor analysis, Pearson's correlations, and multigroup confirmatory factor analysis tests were conducted thereafter. RESULTS: The results showed that the Cronbach's alpha coefficients for the two subscales of the PANSI-positive suicide ideation and the PANSI-negative suicide ideation were .696 and .915, respectively. The confirmatory factor analysis supported the fit of the two-factor model as the best fitting model [Chi-square goodness of fit = 703.859, p < .001, degrees of freedom = 76, comparative fit index = .919, Tucker-Lewis index = .903, standardized root mean square residual = .047, root mean square error of approximation (90% CI) = .083 (.077, .089)]. Positive suicide ideation had negative correlations with the SPS and positive correlations with the RSE, whereas the negative suicide ideation had positive correlations with the SPS and negative correlations with the RSE. All correlations were statistically significant (p < .001), demonstrating the criterion validity of the PANSI-C. Moreover, the strict measurement invariance of the PANSI-C was supported across gender, single-parent and non-single-parent households groups, and the strong measurement invariance was supported across age. LIMITATIONS: The feasibility of this study is limited to Chinese normal adolescents and lack of clinical samples. CONCLUSION: Empirical support for the reliability and validity of the PANSI-C was found. The PANSI-C instrument is found to be useful in assessing positive and negative suicide ideation in Chinese normal adolescents.

Downregulation of hsa_circ_0074854 Suppresses the Migration and Invasion in Hepatocellular Carcinoma via Interacting with HuR and via Suppressing Exosomes-Mediated Macrophage M2 Polarization.

BACKGROUND: Circular RNAs (circRNAs) have been identified as key factors in the development of hepatocellular carcinoma (HCC). However, the role and potential molecular mechanism of circRNAs in HCC remain largely unclear. In addition, exosomes are known as important messengers of the cross-talk between tumor cells and immune cells, while the role of extracellular circRNAs in the cell-to-cell communication of tumor cells and immune cells remains not unclear. METHODS: The level of hsa_circ_0074854 in HCC cell lines and HCC cell-derived exosomes was assessed using RT-qPCR assay. In addition, CCK-8 and transwell assays were used to determine the viability, migration and invasion of HCC cells. RESULTS: Hsa_circ_0074854 expression was upregulated in HCC tissues and HCC cell lines. Additionally, hsa_circ_0074854 knockdown was found to inhibit HCC growth in vitro and in vivo. Mechanistically, hsa_circ_0074854 knockdown inhibited the migration and invasion of HCC cells via interacting with human antigen R (HuR) to reduce its stability. Furthermore, hsa_circ_0074854 can be transferred from HCC cells to macrophages via exosomes. Exosomes with downregulated hsa_circ_0074854 suppressed macrophage M2 polarization, which in turn suppressing migration and invasion of HCC cells both in vitro and in vivo. CONCLUSION: Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Collectively, these findings may help to understand the diagnosis and treatment of HCC.

Elevated α-hydroxybutyrate dehydrogenase as an independent prognostic factor for mortality in hospitalized patients with COVID-19.

AIMS: Many studies have explored the clinical characteristics of patients with coronavirus disease (COVID-19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α-hydroxybutyrate dehydrogenase (α-HBDH) levels on disease progression and prognosis of patients with COVID-19. METHODS AND RESULTS: One thousand seven hundred and fifty-one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α-HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in-hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α-HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID-19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α-HBDH group and 66 years in elevated α-HBDH group (P < 0.001). The mortality during hospitalization was 0.26% (4 of 1559) for patients with normal α-HBDH levels and 5.73% (11 of 192) for those with elevated α-HBDH levels (P < 0.001). Multivariate Cox analysis confirmed an association between elevated α-HBDH levels and higher risk of in-hospital mortality [hazard ratio: 4.411, 95% confidence interval (95% CI), 1.127-17.260; P = 0.033]. Multivariate logistic regression for disease severity and α-HBDH levels showed significant difference between both groups (odds ratio = 3.759; 95% CI, 1.895-7.455; P < 0.001). Kaplan-Meier curves also illustrated the survival difference between normal and elevated α-HBDH patients (P < 0.001). CONCLUSIONS: Our study found that serum α-HBDH is an independent risk factor for in-hospital mortality and disease severity among COVID-19 patients. α-HBDH assessment may aid clinicians in identifying high-risk individuals among COVID-19 patients.

Bilirubin Levels as Potential Indicators of Disease Severity in Coronavirus Disease Patients: A Retrospective Cohort Study.

Objectives: The coronavirus disease (COVID-19) pandemic has caused a large number of deaths. Some patients with severe or critical COVID-19 have been observed to have elevated bilirubin levels. Studies on the association of bilirubin level and mortality in patients with COVID-19 are limited. This study aimed to examine the role of bilirubin levels in COVID-19 severity and mortality. Methods: A retrospective cohort study was conducted in patients hospitalized with COVID-19 in Leishenshan Hospital in Wuhan, China. Cox regression analyses and logistic regression analyses were conducted to investigate the risks for mortality and disease severity, respectively. Kaplan-Meier analyses with log-rank tests were performed to assess the association between bilirubin level and survival. Results: In total, 1,788 patients with COVID-19 were included in the analysis. 5.8% (4/69) of patients in the elevated serum total bilirubin (STB) group died, compared to 0.6% (11/1,719) of patients in the non-elevated STB group. The median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the elevated STB group were 29 U/L [interquartile range (IQR): 16-45 U/L] and 22 U/L (IQR: 13-37 U /L), respectively, which were significantly higher than the median ALT (median: 23, IQR: 15-37) and AST (median: 20, IQR: 16-26) activities in the non-elevated STB group (both p < 0.05). Patients with an elevated STB level showed increased mortality [hazard ratio (HR): 9.45, P = 0.002], elevated conjugated bilirubin (CB) levels (HR: 4.38, P = 0.03), and an elevated ratio of CB to unconjugated bilirubin (UCB, CB/UCB) (HR: 2.49, P = 0.01). CB/UCB was positively correlated with disease severity (odds ratio: 2.21, P = 0.01). Conclusions: COVID-19 patients with elevated STB and CB levels had a higher mortality, and CB/UCB was predictive of disease severity and mortality. Thus, it is necessary to pay special attention to COVID-19 patients with elevated bilirubin levels in clinical management.

Endothelial FGFR1 (Fibroblast Growth Factor Receptor 1) Deficiency Contributes Differential Fibrogenic Effects in Kidney and Heart of Diabetic Mice.

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to organ fibrogenesis. We have reported that N-acetyl-seryl-aspartyl- lysyl-proline (AcSDKP) restored levels of diabetes mellitus-suppressed FGFR1 (fibroblast growth factor receptor 1), the endothelial receptor essential for combating EndMT. However, the molecular regulation and biological/pathological significance of the AcSDKP-FGFR1 relationship has not been elucidated yet. Here, we demonstrated that endothelial FGFR1 deficiency led to AcSDKP-resistant EndMT and severe fibrosis associated with EndMT-stimulated fibrogenic programming in neighboring cells. Diabetes mellitus induced severe kidney fibrosis in endothelial FGFR1-deficient mice (FGFR1fl/fl; VE-cadherin-Cre: FGFR1EKO) but not in control mice (FGFR1fl/fl); AcSDKP completely or partially suppressed kidney fibrosis in control or FGFR1EKO mice. Severe fibrosis was also induced in hearts of diabetic FGFR1EKO mice; however, AcSDKP had no effect on heart fibrosis in FGFR1EKO mice. AcSDKP also had no effect on EndMT in either kidney or heart but partially suppressed epithelial-to-mesenchymal transition in kidneys of diabetic FGFR1EKO mice. The medium from FGFR1-deficient endothelial cells stimulated TGFß (transforming growth factor ß)/Smad-dependent epithelial-to-mesenchymal transition in cultured human proximal tubule epithelial cell line, AcSDKP inhibited such epithelial-to-mesenchymal transition. These data demonstrated that endothelial FGFR1 is essential as an antifibrotic core molecule as the target of AcSDKP.

Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Dynamic Interleukin-6 Level Changes as a Prognostic Indicator in Patients With COVID-19.

BACKGROUND: Interleukin-6 (IL-6), a proinflammatory cytokine, has been reported to be associated with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19). Yet, dynamic changes in IL-6 levels and their prognostic value as an indicator of lung injury in COVID-19 patients have not been fully elucidated. OBJECTIVE: To validate whether IL-6 levels are associated with disease severity and mortality and to investigate whether dynamic changes in IL-6 levels might be a predictive factor for lung injury in COVID-19 patients. METHODS: This retrospective, single-center study included 728 adult COVID-19 patients and used data extracted from electronic medical records for analyses. RESULTS: The mortality rate was higher in the elevated IL-6 group than in the normal IL-6 group (0.16 vs 5%). Cox proportional hazards and logistic regression analyses for survival (adjusted hazard ratio, 10.39; 95% confidence interval [CI], 1.09-99.23; p = 0.042) and disease severity (adjusted odds ratio, 3.56; 95% CI, 2.06-6.19; p < 0.001) revealed similar trends. Curve-fitting analyses indicated that patient computed tomography (CT) scores peaked on days 22 and 24. An initial decline in IL-6 levels on day 16 was followed by resurgence to a peak, nearly in tandem with the CT scores. CONCLUSION: Increased IL-6 level may be an independent risk factor for disease severity and in-hospital mortality and dynamic IL-6 changes may serve as a potential predictor for lung injury in Chinese COVID-19 patients. These findings may guide future treatment of COVID-19 patients.

Association Between Diabetes and COVID-19: A Retrospective Observational Study With a Large Sample of 1,880 Cases in Leishenshan Hospital, Wuhan.

Aims: This study aimed to investigate the clinical courses and outcomes of diabetes mellitus patients with coronavirus disease 2019 (COVID-19) in Wuhan. Methods: This study enrolled 1,880 consecutive patients with confirmed COVID-19 in Leishenshan Hospital. We collected and analyzed their data, including demographic data, history of comorbidity, clinical symptoms, laboratory tests, chest computed tomography (CT) images, treatment options, and survival. Results: The percentages of patients with diabetes among the severe and critical COVID-19 cases were higher than those among the mild or general cases (89.2%, 10.8 vs. 0%, p = 0.001). However, patients with and without diabetes showed no difference in the follow-up period (p = 0.993). The mortality rate in patients with or without diabetes was 2.9% (n = 4) and 1.1% (n = 9), respectively (p = 0.114). Univariate and multivariate Cox regression analyses and the Kaplan-Meier curves did not show any statistically significant differences between patients with and without diabetes (all p > 0.05). Conclusions: Our study results suggested that diabetes had no effect on the prognosis of COVID-19 patients but had a negative association with their clinical courses. These results may be useful for clinicians in the management of diabetic patients with COVID-19.