Contributing Factors Affecting the Length of Hospital Stay among Febrile Patients with Omicron Reported in Suzhou.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Independent and joint trajectories of depression and anxiety symptoms among Chinese male sailors throughout a prolonged non-24-h rotating shift schedule at sea: a parallel-process growth mixture modeling approach.

BACKGROUND: The predictive and protective effect of hardiness on mental health remains unclear among shift workers on non-24-h working schedules. The present study aimed to investigate the independent and joint trajectories of depression and anxiety symptoms and the role of hardiness during a prolonged period of non-24-h shift working schedule. METHODS: Four hundred nine Chinese male sailors (working on 18-h watchstanding schedule) were recruited and completed all 5-wave tests through online questionnaires (at Day 1, 14, 28, 42, 55, respectively) during a 55-day sailing. The questionnaires included sociodemographic variables, hardiness, depression and anxiety symptoms. Independent and joint trajectories of depression and anxiety symptoms were estimated by latent growth mixture models. The effect of hardiness on trajectories was examined by logistic regression models. RESULTS: 2 and 3 latent trajectories were identified for depression and anxiety symptoms, respectively. Based on initial levels and development trends, 3 distinct joint trajectories of depression and anxiety were identifed and named as: "Low-Inverted U" group (73.6%), "Moderate-Deterioration" group (6.9%), and "High-Stable" group (9.5%). Sailors with higher levels of hardiness were more likely to follow the "Low-Inverted U" trajectory of depression and anxiety symptoms (all p < 0.001). CONCLUSIONS: There existed individual differences in the trajectories of depression and anxiety. Hardiness may have a protective effect that can prevent and alleviate depression and anxiety symptoms. Therefore, hardiness-based intervention programs are encouraged among the shift workers on non-24-h working and rest schedules.

Psychometric properties of the Brief Version of Pittsburgh Sleep Quality Index (B-PSQI) among Chinese male sailors on 18-hr rotating shift schedule.

Sleep problems among shift workers have emerged as a public health concern in recent years. However, few validation studies of self-reported sleep quality questionnaires were performed among shift workers. The present study aimed to examine the psychometric properties of the Brief Version of Pittsburgh Sleep Quality Index (B-PSQI) in a shift workers sample. In total, 443 Chinese male sailors were recruited, of whom 46.95% (n = 208) were watchstanding sailors on 18-hr working schedule at sea. All participants completed the B-PSQI, the Insomnia Severity Index (ISI), the Self-Rating Depression Scale, and Self-Rating Anxiety Scale before and after a 30-day saling. Forty watchstanding sailors were selected to wear wrist actigraphy throughout the sailing. The results showed that the B-PSQI had acceptable internal consistency reliability in different sailor groups. Confirmatory factor analysis showed optimal fit of the single-factor model of the B-PSQI in different sailor groups. Furthermore, scalar invariance between watchstanding and day-working sailors was supported, as well as longitudinal scalar invariance across time. In addition, receiver operating characteristic analysis showed that the B-PSQI yields high discrimination power to detect poor sleep quality using ISI ≥ 8 criterion. However, a lack of intermethod agreement across the B-PSQI and actigraphy was found in this study. Moreover, the total scores of B-PSQI were positively related to depression and anxiety symptoms in the present sample. The B-PSQI is a reliable and valid sleep quality measure and a useful screening tool for sleep disorders among Chinese male sailors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Psychometric properties of the 10-item Connor-Davidson Resilience Scale in Chinese military personnel.

Background: The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is a widely used assessment of resilience. However, psychometric properties of the Chinese version of CD-RISC-10 have not been well investigated in a Chinese military personnel sample. Methods: A total of 3,129 Chinese military personnel completed the CD-RISC-10, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Among them, 528 recruits completed the CD-RISC-10, SAS, and SDS again after 3-month basic military training (BMT). Meanwhile, the commanding officers were asked to rate recruits' training performance on the training performance rating scale for recruits (TPRS). Confirmatory factor analysis (CFA) was implemented to examine the single-factor model of the CD-RISC-10, and multigroup CFA was conducted to test measurement invariance across military rank (officers vs. enlisted), gender (male vs. female), and time (before and after 3-month BMT). Internal consistency was evaluated using Cronbach's α and McDonald's ω, and test-retest reliability was tested using the intra-class correlation coefficient (ICC). The criterion-related validity of CD-RISC was evaluated using Pearson's correlation analysis between the CD-RISC-10 total score and SAS scores, SDS scores, and training performance ratings. Results: The single-factor model of the CD-RISC-10 showed adequate fit (CFI = 0.955-0.970, TLI = 0.943-0.962, RMSEA = 0.059-0.072) in all examined subsamples (male, female, officer, and enlisted), and strict invariance was also supported across military rank, gender, and time (ΔCFI ≤ 0.001, ΔTLI ≤ 0.005, ΔRMSEA ≤ 0.006). The CD-RISC-10 showed good internal consistency in all subsamples (Cronbach's α of > 0.93 and McDonald's ω of > 0.93) and good test-retest reliability (ICC = 0.88). Moreover, concurrent and predictive validity with the SAS and SDS scores were good (r = -0.68 to -0.49, p < 0.001). The resilience level of recruits at the beginning of BMT was significantly associated with training performance rated by supervisors after training (r = 0.29, p < 0.001). Conclusion: The psychometric evidence reported in this study suggests that the CD-RISC-10 is a reliable and valid assessment of resilience and a potential predictor for mental health and military performance in Chinese military personnel.

Risk Factors for Radiological Progression Within Admissive One Week in the Hospitalized COVID-19 Omicron Variant-Infected Patients.

Purpose: Recently, the SARS-CoV-2 Omicron variant was identified as responsible for a novel wave of COVID-19 worldwide. We perform a retrospective study to identify potential risk factors contributing to radiological progression in the COVID-19 patients due to the Omicron variant infection. These findings would provide guiding information for making clinical decisions that could improve the Omicron infection prognosis and reduce disease-related death. Methods: This is a retrospective cohort study from a single center in China. According to the radiological change within admissive one week, enrolled cases were divided into two groups: the progressive (1w-PD) and the stable or improved disease (1w-non-PD). Separate analyses were performed on patients stratified into subgroups using the Mann-Whitney U-test, the Fisher exact test, or the Chi-squared test and a multivariable logistic regression analysis. Results: Both the 1w-non-PD and 1w-PD cohorts displayed comparable asymptomatic infection, have similar underlying disease, impairment in respiratory function, coagulation dysfunction, tissue injury, SARS-CoV-2 viral load, and disease severity. However, the 1w-PD cohort was more inclined to cluster in populations presented with age between 41 and 65, higher CURB-65 scores, undetectable SARS-CoV-2 IgG, and lung affection. Based on the multiple logistic regression analysis, complicated bilateral and ground-glass opacities (GGOs) like pneumonia at admission were independent risk factors to radiological progression within admissive one week. Conclusion: This study provided preliminary data regarding disease progression in Omicron-infected patients that indicated the development of pneumonia in the context of Omicron infection was worthy of potential risk factors.

[Retracted] Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice.

[This retracts the article DOI: 10.3892/etm.2016.3236.].

Potentially traumatic events and post-traumatic growth among Chinese peacekeepers: A moderated mediation model.

Peacekeepers are inherently exposed to potentially traumatic events (PTEs) in the line of duty. However, little is known about whether PTEs during peacekeeping missions may foster post-traumatic growth (PTG) among peacekeepers and its mechanisms. This study aimed to investigate the association between PTEs and PTG among Chinese peacekeepers, as well as the mediating role of coping style and the moderating role of resilience. Five hundred ninety-five Chinese peacekeepers completing the United Nations (UN) peacekeeping mission in South Sudan and returning to China were recruited to complete Peacekeeping Traumatic Stress Exposure Scale, Posttraumatic Growth Inventory, Simplified Coping Style Questionnaire and the Chinese version of Connor and Davidson's Resilience Scale. PTEs were positively associated with PTG among Chinese peacekeepers. Coping style partially mediated the association between PTEs and PTG. Resilience moderated the association between coping style and PTG. Specifically, at a lower level of resilience, positive coping style was more effective in predicting PTG. This study contributes to understanding the complex association between PTEs in peacekeeping missions, coping style, resilience and PTG by focusing on the experiences of Chinese peacekeepers and adds value to the current literature on psychological health in peacekeepers.

Autologous Cytokine-Induced Killer Cell Immunotherapy Enhances Chemotherapy Efficacy against Multidrug-Resistant Tuberculosis.

Objective: Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients. Preclinical mouse studies have shown that the adoptive T cell therapy inhibited Mtb infection. However, the efficacy of CIK immunotherapy in the treatment of MDR-TB infection has not been evaluated in clinical trials. Methods: We performed a retrospective study of MDR-TB patients who received CIK immunotherapy in combination with anti-TB chemotherapy and those who had standard chemotherapy. Results: Our results showed that CIK immunotherapy in combination with anti-TB chemotherapy treatment increased the conversion rate of sputum smear and Mtb culture, alleviated symptoms, improved lesion absorption, and increased recovery. The kinetics of serology and immunology index monitoring data showed good safety profiles for the CIK treatment. Conclusion: Our study has provided strong evidence that CIK immunotherapy in combination with anti-TB chemotherapy is beneficial for MDR-TB patients. A multicenter clinical trial is warranted to evaluate CIK as a new immune therapy for MDR-TB.

Epidemiology of concurrent extrapulmonary tuberculosis in inpatients with extrapulmonary tuberculosis lesions in China: a large-scale observational multi-centre investigation.

AIMS: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. METHODS: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. RESULTS: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). CONCLUSIONS: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Driver-passenger communicative stress and psychological distress among Chinese bus drivers: the mediating effect of job burnout.

BACKGROUND: This study aimed to investigate the relationship between driver-passenger communicative stress and psychological distress among bus drivers, as well as whether job burnout mediates the effect of driver-passenger communicative stress on psychological distress. METHODS: A questionnaire consisting of a 12-item version of the General Health Questionnaire (GHQ-12), a one-item driver-passenger communicative stress scale, the Maslach Burnout Inventory-General Survey (MBI-GS), as well as sociodemographic and work factors, was distributed to 310 bus drivers in Shanghai, of which 307 completed it (99.0% response rate). A parallel multiple mediation model with bootstrap approach, was calculated to test the mediating effect. RESULTS: Driver-passenger communicative stress, emotional exhaustion and cynicism were positively associated with psychological distress. Communicative stress was significantly positively linked with two of the three dimensions of burnout (emotional exhaustion and cynicism) and dependent variable. Emotional exhaustion and cynicism were positively associated with the dependent variable. The results indicate that emotional exhaustion and cynicism partially mediated the effect of communicative stress on psychological health, and that 60.0% of this effect can be explained by mediating effects, in which emotional exhaustion and cynicism weighed 63.2% and 36.8%, respectively. CONCLUSIONS: Communicative stress had effects on psychological distress among Chinese bus drivers, and job burnout was a mediator in this relationship.

Factors associated with delayed viral shedding in COVID-19 infected patients: A retrospective small-scale study.

BACKGROUND: The outbreak of COVID-19 has caused ever-increasing attention and public panic all over the world. Until now, data are limited about the risk factors to virus shedding in COVID-19 infected patients. METHODS: In this retrospective study, data were collected from 87 patients hospitalized with COVID-19 infection in Suzhou. Using Cox proportional hazards regression and Kaplan-Meier survival analysis, the risk factors to COVID-19 RNA shedding was to be established according to demographic information, clinical characteristics, epidemiological history, antiviral medicine and corticosteroid administration. RESULTS: The median duration of COVID-19 RNA shedding from admission was 13.11 ± 0.76 days. There was no significant difference in viral shedding duration in terms of gender, age, history of Hubei province stay, characteristics of chest CT on admission, lymphocytopenia and clinical severity. By Cox proportional hazards model, excessive 200 mg cumulative corticosteroid (HR, 3.425 [95% CI, 1.339-7.143]), time from illness onset to hospitalization (<5 days) (HR, 2.503 [95% CI, 1.433-4.371]) and arbidol-included therapy (HR, 2.073 [95% CI, 1.185-3.626]) were the independent risk factors to delay COVID-19 RNA shedding. Besides of excessive 200 mg of cumulative corticosteroid (HR, 2.825 [95% CI, 1.201-6.649]), admission within 5 days from illness onset (HR, 2.493 [95% CI, 1.393-4.462]) and arbidol-included therapy (HR, 2.102 [95% CI, 1.073-4.120]), lymphocytopenia (HR, 2.153 [95% CI, 1.097-4.225]) was further identified as another unfavorable factor to 10-day viral shedding. CONCLUSIONS: The potential risk factors could help clinicians to identify patients with delayed viral shedding, thereby providing the rational strategy of treatment and optimal anti-viral interventions.

Clinical characteristics and laboratory indicator analysis of 67 COVID-19 pneumonia patients in Suzhou, China.

BACKGROUND: Sudden exacerbations and respiratory failure are major causes of death in patients with severe coronavirus disease 2019(COVID-19) pneumonia, but indicators for the prediction and treatment of severe patients are still lacking. METHODS: A retrospective analysis of 67 collected cases was conducted and included approximately 67 patients with COVID-19 pneumonia who were admitted to the Suzhou Fifth People's Hospital from January 1, 2020 to February 8, 2020. The epidemiological, clinical and imaging characteristics as well as laboratory data of the 67 patients were analyzed. RESULTS: The study found that fibrinogen (FIB) was increased in 45 (65.2%) patients, and when FIB reached a critical value of 4.805 g/L, the sensitivity and specificity、DA, helping to distinguish general and severe cases, were 100 and 14%、92.9%, respectively, which were significantly better than those for lymphocyte count and myoglobin. Chest CT images indicated that the cumulative number of lung lobes with lesions in severe patients was significantly higher than that in general patients (P < 0.05), and the cumulative number of lung lobes with lesions was negatively correlated with lymphocyte count and positively correlated with myoglobin and FIB. Our study also found that there was no obvious effect of hormone therapy in patients with severe COVID-19. CONCLUSIONS: Based on the retrospective analysis, FIB was found to be increased in severe patients and was better than lymphocyte count and myoglobin in distinguishing general and severe patients. The study also suggested that hormone treatment has no significant effect on COVID-19.

No intrauterine vertical transmission in pregnancy with COVID-19: A case report.

The coronavirus disease 2019 (COVID-19) has been a worldwide pandemic diseases, nearly 400,000 people died at now. The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. The SARS-COV-2 nucleic acid test results of these specimens were negative. There is no evidence of intrauterine vertical transmission during delivery in the third trimester, but the data are limited and need to be further explored.

Circulating Receptor-Interacting Protein Kinase 3 Are Increased in HBV Patients With Acute-on-Chronic Liver Failure and Are Associated With Clinical Outcome.

BACKGROUND AND AIMS: Necroptosis is a newly identified type of cell death with programmed pathways. The current study was performed to investigate necroptosis by measuring its key regulators; receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) in patients with Hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF). METHODS: HBV-related ACLF (HBV-ACLF) patients (n = 90), non-ACLF patients without cirrhosis (N = 70), patients with cirrhosis (N = 40), and healthy controls (HCs; n = 70) were enrolled in the study. All patients were subject to serum RIPK3 measurement. Hepatic RIPK3 and MLKL were also determined in the livers of 18 patients and five donors, using immunohistochemistry. RESULTS: Serum RIPK3 was significantly elevated in HBV-ACLF patients compared to that of non-ACLF patients and the HCs. Serum RIPK3 in ACLF patients at recruitment was significantly higher in non-survivors than those in survivors at the 90-day follow-up. The predictive accuracy of serum RIPK3 at the 90-day outcome was relatively good with an area under the receiver operating curve (AUROC) of 0.72 (p < 0.001), similar to that of the model of end-staged liver disease (MELD) score (0.76, p < 0.001). The combined use of RIPK3 and MELD score further increased the AUROC to 0.80. The hepatic RIPK3 and MLKL measured by immunohistochemistry, significantly increased in the patients with HBV-ACLF than in the patients without ACLF and the HCs. CONCLUSION: Circulating RIPK3 was significantly increased in patients with HBV-ACLF and was associated with a clinical outcome. The improved combined objective scores could offer additional prognostic value in ACLF patients, for physicians with more accurate expectations.

A Case of 2019 Novel Coronavirus in a Pregnant Woman With Preterm Delivery.

We present a case of a 30-week pregnant woman with the 2019 novel coronavirus (COVID-19) delivering a healthy infant with no evidence of COVID-19.

Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus.

OBJECTIVES: To evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with avian influenza A (H7N9) virus. DESIGN: Retrospective cohort study. SETTING: A total of 133 hospitals in 17 provinces, autonomous regions, and municipalities of mainland China that admitted influenza A (H7N9) virus-infected patients between January 22, 2015, and June 16, 2017. PATIENTS: A total of 321 patients with influenza A (H7N9) virus infection were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics and clinical characteristics were collected from medical records. Cardiac injury was defined according to cardiac biomarkers, electrocardiography, or echocardiography. Among the 321 patients, 203 (63.2%) showed evidence of cardiac injury. Compared with the uninjured group, the cardiac injury group had lower PaO2/FIO2 (median, 102.0 vs 148.4 mm Hg; p < 0.001), higher Acute Physiology and Chronic Health Evaluation II score (median, 17.0 vs 11.0; p < 0.001), longer stay in the ICU (10.0 vs 9.0 d; p = 0.029), and higher proportion of in-hospital death (64.0% vs 20.3%; p < 0.001). The proportion of virus clearance until discharge or death was lower in the cardiac injury group than in the uninjured group (58.6% vs 86.4%; p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality (hazards ratio, 2.06; 95% CI, 1.31-3.24) during hospitalization. CONCLUSIONS: Cardiac injury is a frequent condition among hospitalized patients infected with influenza A (H7N9) virus, and it is associated with higher risk of mortality.

IL-36ß Promotes CD8+ T Cell Activation and Antitumor Immune Responses by Activating mTORC1.

Cytokine-amplified functional CD8+ T cells ensure effective eradication of tumors. Interleukin 36α (IL-36α), IL-36ß, and IL-36γ share the same receptor complex, composed of the IL-36 receptor (IL-36R), and IL-1RAcP. Recently, we revealed that IL-36γ greatly promoted CD8+ T cell activation, contributing to antitumor immune responses. However, the underlying mechanism of IL-36-mediated CD8+ T cell activation remains understood. In the current study, we proved that IL-36ß had the same effect on CD8+ T cell as IL-36γ, and uncovered that IL-36ß significantly activated mammalian target of rapamycin complex 1 (mTORC1) of CD8+ T cells. When mTORC1 was inhibited by rapamycin, IL-36ß-stimulated CD8+ T cell activation and expansion was drastically downregulated. Further, we elucidated that IL-36ß-mediated mTORC1 activation was dependent on the pathway of phosphatidylinositol 3 kinase (PI3K)/Akt, IκB kinase (IKK) and myeloid differentiation factor 88 (MyD88). Inhibition of PI3K or IKK by inhibitor, or deficiency of MyD88, respectively, suppressed mTORC1 signal, causing arrest of CD8+ T cell activation. Additionally, it was validated that IL-36ß significantly promoted mTORC1 activation and antitumor function of CD8+ tumor-infiltrating lymphocytes (TILs) in vivo, resulting in inhibition of tumor growth and prolongation of survival of tumor-bearing mice. Taken together, we substantiated that IL-36ß could promote CD8+ T cell activation through activating mTORC1 dependent on PI3K/Akt, IKK and MyD88 pathways, leading to enhancement of antitumor immune responses, which laid the foundations for applying IL-36ß into tumor immunotherapy.

Expression and clinical significance of B and T lymphocyte attenuator on CD4+ and CD8+ T cells from patients with pulmonary tuberculosis.

BACKGROUND: As an immune checkpoint, upregulation of B and T lymphocyte attenuator (BTLA) contributes to T-cell exhaustion in chronic infection. However, the characteristics of BTLA on T cells of patients with pulmonary tuberculosis (PTB) are still uncovered. AIMS: The aim of the study was to elucidate the dynamics and clinical significance of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients. MATERIALS AND METHODS: BTLA expression on T cells from PTB patients with smear positivity (n = 86) and healthy controls (HCs) (n = 40) were determined using flow cytometry. RESULTS: The levels of BTLA expression on circulating CD4+ and CD8+ T cells of PTB patients with smear positivity were both upregulated, compared with HC. At the same time, the levels of BTLA expression on CD4+ and CD8+ T cells of patients with retreatment were both higher than that of those with initial treatment and gradually upregulated along with the increase of the bacillary load in sputum. In addition, the patients with lung cavity were discovered to present higher levels of BTLA expression on CD4+ and CD8+ T cells than those without lung cavity. Whereas we noted that there was no correlation between the levels of BTLA expression and the positivity or negativity of anti-Mycobacterium tuberculosis antibody. CONCLUSIONS: The levels of BTLA expression were upregulated on CD4+ and CD8+ T cells of PTB patients and associated with disease progression. Thereby, BTLA expression on T cells may be considered as a potential clinical indicator and utilized as a therapeutic target for PTB.

Discrepant Clinical Significance of CD28+CD8- and CD4+CD25high Regulatory T Cells During the Progression of Hepatitis B Virus Infection.

Accumulating evidence demonstrates that CD8+CD28- regulatory T cells increase in chronic viral infection as well as tumorigenesis. However, it is still not clear about their characteristics in hepatitis B virus (HBV) infection. In addition, it is not understood whether this regulatory immune subset is distinct from CD4+CD25high regulatory T cells in the aspect of impact on or relationship to the progression of HBV infection. Hence, we investigated their dynamics and compared their correlations with clinical parameters in the chronic and advanced phases of HBV infection. The data showed that compared with healthy controls, the frequencies of CD28+CD8- and CD4+CD25high T cells increased in both chronic and advanced phases, while there is no significant difference between the two case groups. Interestingly, we found that in chronic phase, the frequency of CD8+CD28- subset was negatively correlated with the levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST), respectively, and did not present association with HBV DNA load, whereas that of CD4+CD25high T cells was positively correlated with HBV DNA load and the levels of ALT and AST, respectively. Amazingly, in advanced phase, the frequency of CD4+CD25high T cells was negatively correlated with HBV DNA load and the levels of ALT, respectively, while there is no significant correlation between the frequency of CD8+CD28- subset and those clinical parameters. Thereby, our findings demonstrated that CD28+CD8- and CD4+CD25high regulatory T cells might exert distinct effect on modulating antiviral immune responses and mitigate immunomediated liver damage in different phases of HBV infection, which represent potential prognostic markers and therapeutic targets for HBV-infected patients based on further exploration of detailed mechanism.