The colonic interleukin-19 aggravates the dextran sodium sulfate/stress-induced comorbidities due to colitis and anxiety

Comorbidities due to inflammatory bowel disease (IBD) and anxiety are commonly acknowledged;however, their underlying basis is unclear. In the current study, we first conducted a clinical retrospective analysis to identify the enhancive incidence rate of IBD before or after the epidemic of Corona Virus Disease 2019 (COVID-19), with higher Generalized Anxiety Disorder-7 (GAD-7), as well as poorer Gastrointestinal Quality of Life Index (GIQLI). Then, the dextran sodium sulfate (DSS) and chronic unpredictable stress (CUS)-induced IBD and anxiety comorbid models were established with the correlational relations between symptoms of IBD and anxiety-related behaviors. We found dysfunctional up-regulation of a new inflammatory factor interleukin (IL)-19 in the colon of DSS/CUS treated mice. Overexpression of IL-19 in colon induced anxious phenotypes, and accelerated the anxious condition and symptoms of colitis in the DSS/CUS model by promoting the expression of inducible nitric oxide synthase (iNOS), IL-1β, and IL-6 pro-inflammatory factors, and activating signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon. Furthermore, overexpression of IL-19 in the colon also reduced the expression levels of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), and cAMP-response element binding protein (CREB) signaling pathways activity in the hippocampus. These results suggest that IL-19 was a pivotal player in DSS/CUS-induced comorbidities of colitis and anxiety with different signaling pathways for the colon and hippocampus, which provides a candidate gene to explore the pathophysiology of comorbidities due to colitis and anxiety.

Comparative Pharmacological Efficacy of COVID-19 Vaccines against the Variants of Concerns (VOCs) of SARS-CoV-2: Recent Clinical Studies on Booster Dose.

Sera obtained from convalescent individuals, and vaccinated individuals can induce low neutralizing efficacy against variants of concerns (VOCs) of SARS-CoV-2. In addition, the majority of COVID-19 vaccines are less efficacious against VOCs when compared to their efficacy against the original virus. Immune escape is one of the significant mechanisms observed during SARS-CoV-2 infection due to the substantial mutational capacity of VOCs such as B.1.1.7, P.1, B.1.351, B.1.617.2, C.37, and B.1.621. Omicron, a novel strain of SARS-CoV-2, also referred to as B.1.1.529, was identified in South Africa. This variant is a potential new VOC by the World Health Organization (WHO), and confirmed cases have been arising across several nations due to its rapid spreading ability. Omicron variant can acquire substantial immune escape following Delta, Beta/Gamma D614G VOCs and subsequently facilitating potential infectivity due to its enhanced ACE2 binding ability. The Omicron variant is a highly mutated variant accompanied by higher transmissibility and immune evasion. This mini review describes the ability of VOCs to acquire immune escape and also describes the comparative neutralization efficacy of several vaccines, including Booster doses against SARS-CoV-2.

Psychological symptoms and correlates of Chinese healthcare professionals in the intensive care unit before and after the COVID-19 outbreak: A comparison of two cross-sectional studies.

BACKGROUND: The outbreak of COVID-19 disarranged lives across mainland China. No study has examined changes in psychological symptoms of healthcare professionals in the intensive care unit (ICU) before and after the outbreak of COVID-19. The aim of this study was to estimate changes in psychological symptoms of ICU healthcare professionals before and after the COVID-19 outbreak, and to analyze factors related to psychological symptoms. METHODS: Two waves' administrations were implemented between December 13 and December 14, 2018, and between April 5 and April 7, 2020, respectively. The symptom checklist-90 (SCL-90) were used to evaluate psychological symptoms. Multiple logistical regression was used to reveal the risk of psychological symptoms. RESULTS: A total of 3902 and 3908 ICU healthcare professionals took part in the first and second surveys. The mean total score of the SCL-90 was 179.27 (70.02) at wave 1 and 147.75 (58.40) at wave 2, respectively. The proportion of psychological symptoms was 55.6 % (95%CI = 54.0-57.1) at wave 1. But rates of psychological symptoms decreased to 36.6 % (95%CI = 35.1-38.2) at wave 2. ICU healthcare professionals with western economic belt and 6-10 years of work were more likely to develop psychological symptoms, while ICU healthcare professionals with the later survey and doctoral degree were less likely to develop psychological symptoms. CONCLUSION: Although COVID-19 period benefited psychological symptoms of ICU healthcare professionals, psychological symptoms still had a related high prevalence. Regular screening and appropriate interventions should still be implemented to decrease the risk for psychological symptoms among Chinese ICU healthcare professionals.

The colonic interleukin-19 aggravates the dextran sodium sulfate/stress-induced comorbidities due to colitis and anxiety.

Comorbidities due to inflammatory bowel disease (IBD) and anxiety are commonly acknowledged; however, their underlying basis is unclear. In the current study, we first conducted a clinical retrospective analysis to identify the enhancive incidence rate of IBD before or after the epidemic of Corona Virus Disease 2019 (COVID-19), with higher Generalized Anxiety Disorder-7 (GAD-7), as well as poorer Gastrointestinal Quality of Life Index (GIQLI). Then, the dextran sodium sulfate (DSS) and chronic unpredictable stress (CUS)-induced IBD and anxiety comorbid models were established with the correlational relations between symptoms of IBD and anxiety-related behaviors. We found dysfunctional up-regulation of a new inflammatory factor interleukin (IL)-19 in the colon of DSS/CUS treated mice. Overexpression of IL-19 in colon induced anxious phenotypes, and accelerated the anxious condition and symptoms of colitis in the DSS/CUS model by promoting the expression of inducible nitric oxide synthase (iNOS), IL-1ß, and IL-6 pro-inflammatory factors, and activating signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon. Furthermore, overexpression of IL-19 in the colon also reduced the expression levels of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase (ERK), and cAMP-response element binding protein (CREB) signaling pathways activity in the hippocampus. These results suggest that IL-19 was a pivotal player in DSS/CUS-induced comorbidities of colitis and anxiety with different signaling pathways for the colon and hippocampus, which provides a candidate gene to explore the pathophysiology of comorbidities due to colitis and anxiety.

Nervous system manifestations related to COVID-19 and their possible mechanisms.

In December 2019, the novel coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection broke. With the gradual deepening understanding of SARS-CoV-2 and COVID-19, researchers and clinicians noticed that this disease is closely related to the nervous system and has complex effects on the central nervous system (CNS) and peripheral nervous system (PNS). In this review, we summarize the effects and mechanisms of SARS-CoV-2 on the nervous system, including the pathways of invasion, direct and indirect effects, and associated neuropsychiatric diseases, to deepen our knowledge and understanding of the relationship between COVID-19 and the nervous system.

Multifaceted Effects and Mechanisms of N-Acetylcysteine on Intestinal Injury in a Porcine Epidemic Diarrhea Virus-Infected Porcine Model.

SCOPE: This study investigates the potential effects of N-acetylcysteine (NAC) on intestinal injury in a porcine epidemic diarrhea virus (PEDV)-infected porcine model. METHODS AND RESULTS: Thirty-two piglets are randomly assigned to one of four groups: the control, PEDV, NAC, and NAC+PEDV. Piglets in the NAC+PEDV group are orally administrated with NAC (100 mg (kg·BW)-1  day-1 ) for 4 consecutive days after 2 days of PEDV infection. The results show that NAC administration decreases the diarrhea rate and improves intestinal morphology. The concentration of diamine oxidase and intestinal fatty-acid binding protein, as well as IL-1ß, IL-8, and TNF-α in the plasma, is decreased by NAC. Intriguingly, NAC administration significantly increases the viral load in the jejunum and ileum and down-regulates the expression of interferon-related genes. Microarray and proteomic analyses show that the differentially expressed genes/proteins between NAC+PEDV and PEDV groups are highly enriched in substance transport. Furthermore, aquaporin 8/10 expression is significantly increased by NAC upon PEDV infection. CONCLUSION: NAC administration alleviates PEDV-induced intestinal injury by inhibiting inflammatory responses and improving substance transport, but promotes viral replication by inhibiting interferon signaling. These results suggest NAC exhibits multifaceted effects upon PEDV infection, and thus caution is required when using NAC as a dietary supplement to prevent viral infection.

Trait Anxiety Mediates Impulsivity and Suicidal Ideation in Depression During COVID-19 Pandemic.

Suicidality in patients with major depressive disorder (MDD) has been an urgent affair during the COVID-19 pandemic. It is well-established that impulsivity and trait anxiety are two risk factors for suicidal ideation. However, literature is still insufficient on the relationships among impulsivity, (state/trait) anxiety and suicidal ideation in individuals with MDD. The present study aims to explore the relationships of these three variables in MDD patients during the COVID-19 pandemic through three scales, including Barrett Impulsivity Scale (BIS), State-Trait Anxiety Scale (STAI) and Self-rating Idea of Suicide Scale (SIOSS). Sixty-three MDD patients (low SIOSS group and high SIOSS group, which were split by the mean score of SIOSS) and twenty-seven well-matched healthy controls were analyzed. Our results showed that the high SIOSS group had higher trait anxiety (p < 0.001, 95% CI = [-19.29, -5.02]) but there was no difference in state anxiety (p = 0.171, 95% CI = [-10.60, 1.25]), compared with the low SIOSS group. And the correlation between impulsivity and suicidal ideation was significant in MDD patients (r = 0.389, p = 0.002), yet it was not significant in healthy controls (r = 0.285, p = 0.167). Further, mediation analysis showed that trait anxiety significantly mediate impulsivity and suicidal ideation in patients with depression (total effect: ß = 0.304, p = 0.002, 95% CI = [0.120, 0.489]; direct effect: ß = 0.154, p = 0.076, 95% CI = [-0.169, 0.325]), indicating impulsivity influenced suicidal ideation through trait anxiety in MDD patients. In conclusion, our results suggested that trait anxiety might mediate the association of impulsivity and suicidal ideation in MDD patients. Clinicians may use symptoms of trait anxiety and impulsivity for screening when actively evaluating suicidal ideation in MDD patients, especially in the setting of COVID-19 pandemic.

Investigation on the Mental Health Status of ICU Practitioners and Analysis of Influencing Factors During the Stable Stage of COVID-19 Epidemic in China.

Objective: To understand the impact of COVID-19 epidemic on the mental health status of intensive care unit (ICU) practitioners in China, and to explore the relevant factors that may affect the mental health status of front-line medical workers so as to adopt efficient and comprehensive measures in a timely manner to protect the mental health of medical staff. Methods: The study covered most of the provinces in China, and a questionnaire survey was conducted based on the WeChat platform and the Wenjuanxing online survey tool. With the method of anonymous investigation, we chose ICU practitioners to participate in the investigation from April 5, 2020 to April 7, 2020. The respondents were divided into two groups according to strict criteria of inclusion and exclusion, those who participated in the rescue work of COVID-19 (COVID-19 group) and those who did not (non-COVID-19 group). The SCL-90 self-evaluation scale was used for the evaluation of mental health status of the subjects. Results: A total of 3,851 respondents completed the questionnaire. First, the overall mental health status of the targeted population, compared with the Chinese norm (n = 1,388), was reflected in nine related factor groups of the SCL-90 scale, and significant differences were found in every factor in both men and women, except for the interpersonal sensitivity in men. Second, the overall mental health of the non-COVID-19 group was worse than that of the COVID-19 group by the SCL-90 scale (OR = 1.98, 95% CI, 1.682-2.331). Third, we have revealed several influencing factors for their mental health in the COVID-19 group, current working status (P < 0.001), satisfaction of diet and accommodation (P < 0.05), occupational exposure (P = 0.005), views on the risk of infection (P = 0.034), and support of training (P = 0.01). Conclusion: The mental health status of the ICU practitioners in the COVID-19 group is better than that of the non-COVID-19 group, which could be attributed to a strengthened mentality and awareness of risks related to occupational exposure and enforced education on preventive measures for infectious diseases, before being on duty.

A deep-learning-based framework for severity assessment of COVID-19 with CT images.

Millions of positive COVID-19 patients are suffering from the pandemic around the world, a critical step in the management and treatment is severity assessment, which is quite challenging with the limited medical resources. Currently, several artificial intelligence systems have been developed for the severity assessment. However, imprecise severity assessment and insufficient data are still obstacles. To address these issues, we proposed a novel deep-learning-based framework for the fine-grained severity assessment using 3D CT scans, by jointly performing lung segmentation and lesion segmentation. The main innovations in the proposed framework include: 1) decomposing 3D CT scan into multi-view slices for reducing the complexity of 3D model, 2) integrating prior knowledge (dual-Siamese channels and clinical metadata) into our model for improving the model performance. We evaluated the proposed method on 1301 CT scans of 449 COVID-19 cases collected by us, our method achieved an accuracy of 86.7% for four-way classification, with the sensitivities of 92%, 78%, 95%, 89% for four stages. Moreover, ablation study demonstrated the effectiveness of the major components in our model. This indicates that our method may contribute a potential solution to severity assessment of COVID-19 patients using CT images and clinical metadata.

SCOAT-Net: A novel network for segmenting COVID-19 lung opacification from CT images.

Automatic segmentation of lung opacification from computed tomography (CT) images shows excellent potential for quickly and accurately quantifying the infection of Coronavirus disease 2019 (COVID-19) and judging the disease development and treatment response. However, some challenges still exist, including the complexity and variability features of the opacity regions, the small difference between the infected and healthy tissues, and the noise of CT images. Due to limited medical resources, it is impractical to obtain a large amount of data in a short time, which further hinders the training of deep learning models. To answer these challenges, we proposed a novel spatial- and channel-wise coarse-to-fine attention network (SCOAT-Net), inspired by the biological vision mechanism, for the segmentation of COVID-19 lung opacification from CT images. With the UNet++ as basic structure, our SCOAT-Net introduces the specially designed spatial-wise and channel-wise attention modules, which serve to collaboratively boost the attention learning of the network and extract the efficient features of the infected opacification regions at the pixel and channel levels. Experiments show that our proposed SCOAT-Net achieves better results compared to several state-of-the-art image segmentation networks and has acceptable generalization ability.

Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The nucleotide analogue prodrug remdesivir was among the first antiviral therapies to be tested in randomized controlled trials (RCTs) for COVID-19. We performed a meta-analysis to understand efficacy and safety. METHODS: We searched PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov databases (from January 1, 2020 to November 5, 2020). We included RCTs comparing the efficacy and safety of remdesivir to control/placebo in COVID-19. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. RESULTS: A total of 4 RCTs with 7334 patients with COVID-19 were included. At a follow-up of 28-29 days from randomization, very low certainty evidence showed that use of remdesivir compared with control group (placebo and/or standard of care) was not associated with a significant decrease in time to clinical improvement (standardized mean difference -0.80 day; [CI, -2.12, 0.53]). However, moderate certainty of evidence showed that remdesivir was associated with higher rates of recovered patients (risk difference [RD] 0.07 [0.05, 0.08]) and discharged patients (RD 0.07 [0.03, 0.11]) and lower rates of developing serious adverse events (RD -0.05 [-0.10, -0.01]) compared with control. Moderate and very low certainty of evidence showed there was no significant difference in deaths at 28-29 days follow-up (RD -0.01 [-0.03, 0.01]) and developing any adverse events (RD 0.01 [-0.17, 0.19]) between both groups, respectively. CONCLUSION: Patients given remdesivir are more likely to demonstrate recovery and were associated with higher rates of hospital discharge, but not with significant reduction in mean time to clinical improvement or mortality.

The Relationship of COVID-19 Severity with Cardiovascular Disease and Its Traditional Risk Factors: A Systematic Review and Meta-Analysis.

BACKGROUND: Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. METHODS: We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. RESULTS: Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >~5 in >60-65 versus <50 years. Three studies showed no change in the RR of age after adjusting for covariate(s). In univariate analyses, factors robustly associated with severe COVID-19 were male sex (10 studies; pooled RR = 1.73, [95% CI 1.50-2.01]), hypertension (8 studies; 2.87 [2.09-3.93]), diabetes (9 studies; 3.20 [2.26-4.53]), and CVD (10 studies; 4.97 [3.76-6.58]). RR for male sex was likely to be independent of age. For the other three factors, meta-regression analyses suggested confounding by age. Only four studies reported multivariable analysis, but most of them showed adjusted RR ~2 for hypertension, diabetes, and CVD. No study explored renin-angiotensin system inhibitors as a risk factor for severe COVID-19. CONCLUSIONS: Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be informative for predicting the risk of severe COVID-19.