Immunomodulatory effects of complex probiotics on the immuno-suppressed mice induced by cyclophosphamide.

Introduction: Previous studies have reported the beneficial effects of Bifidobacterium animalis subsp. lactis XLTG11, Lacticaseibacillus casei Zhang, and Lactiplantibacillus plantarum P8, respectively. However, studies on the immunomodulatory enhancing effects of three complex probiotics have not been conducted. The aim of our study is to investigate the immunomodulatory effects of complex probiotics effect on the immunosuppressed mice induced by cyclophosphamide (CTX). Methods: An immunocompromised mouse model was established by intraperitoneal injection of cyclophosphamide, which was gavage of different doses of complex probiotics and levamisole hydrochloride. The splenic and thymic indices, intestinal barrier, leukocyte and lymphocyte counts, percentage of splenic lymphocyte subpopulations, cytokine levels, and gut microbiota were determined. Results: Results showed that the complex probiotics significantly elevated the spleen and thymus indices, increased the villi and crypt depth and the goblet cells. The leukocyte and lymphocyte counts and the percentage of splenic lymphocyte subpopulations in the CTX-treated mice were significantly elevated by the complex probiotics. In addition, the cytokines (IL-6, IL-10, IL-1ß, and IFN-γ) were significantly increased after complex probiotic treatment. The complex probiotics restored the gut microbiota structure to the pattern of the control group by reducing the ratio of Firmicutes/Bacteroidetes and enhancing the relative abundances of specific microbiota that produced short-chain fatty acids. Discussion: This study provides theoretical support for the immunity-enhancing function of the complex probiotics as well as a pharmacological basis for its further development and utilization.

The role of IL-6 in coronavirus, especially in COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects both people and animals and may cause significant respiratory problems, including lung illness: Corona Virus Disease 2019 (COVID-19). Swabs taken from the throat and nose of people who have the illness or are suspected of having it have shown this pathogenic virus. When SARS-CoV-2 infects the upper and lower respiratory tracts, it may induce moderate to severe respiratory symptoms, as well as the release of pro-inflammatory cytokines including interleukin 6 (IL-6). COVID-19-induced reduction of IL-6 in an inflammatory state may have a hitherto undiscovered therapeutic impact. Many inflammatory disorders, including viral infections, has been found to be regulated by IL-6. In individuals with COVID-19, one of the primary inflammatory agents that causes inflammatory storm is IL-6. It promotes the inflammatory response of virus infection, including the virus infection caused by SARS-CoV-2, and provides a new diagnostic and therapeutic strategy. In this review article, we highlighted the functions of IL-6 in the coronavirus, especially in COVID-19, showing that IL-6 activation plays an important function in the progression of coronavirus and is a rational therapeutic goal for inflammation aimed at coronavirus.

The role of IL-6 in coronavirus, especially in COVID-19

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects both people and animals and may cause significant respiratory problems, including lung illness: Corona Virus Disease 2019 (COVID-19). Swabs taken from the throat and nose of people who have the illness or are suspected of having it have shown this pathogenic virus. When SARS-CoV-2 infects the upper and lower respiratory tracts, it may induce moderate to severe respiratory symptoms, as well as the release of pro-inflammatory cytokines including interleukin 6 (IL-6). COVID-19-induced reduction of IL-6 in an inflammatory state may have a hitherto undiscovered therapeutic impact. Many inflammatory disorders, including viral infections, has been found to be regulated by IL-6. In individuals with COVID-19, one of the primary inflammatory agents that causes inflammatory storm is IL-6. It promotes the inflammatory response of virus infection, including the virus infection caused by SARS-CoV-2, and provides a new diagnostic and therapeutic strategy. In this review article, we highlighted the functions of IL-6 in the coronavirus, especially in COVID-19, showing that IL-6 activation plays an important function in the progression of coronavirus and is a rational therapeutic goal for inflammation aimed at coronavirus.

Age and Comorbidities Predict COVID-19 Outcome, Regardless of Innate Immune Response Severity: A Single Institutional Cohort Study

OBJECTIVES: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome coronavirus 2–induced hyperinflammation is one of the mechanisms underlying the high mortality, the association between age and innate immune responses in COVID-19 mortality remains unclear. DESIGN: Flow cytometry of fresh blood and multiplexed inflammatory chemokine measurements of sera were performed on samples collected longitudinally from our cohort. Aggregate impact of comorbid conditions was calculated with the Charlson Comorbidity Index, and association between patient factors and outcomes was calculated via Cox proportional hazard analysis and repeated measures analysis of variance. SETTING: A cohort of severely ill COVID-19 patients requiring ICU admission was followed prospectively. PATIENTS: In total, 67 patients (46 male, age 59 ± 14 yr) were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality in our cohort was 41.8%. We identified older age (hazard ratio [HR] 1.09 [95% CI 1.07–1.11];p = 0.001), higher comorbidity index (HR 1.24 [95% CI 1.14–1.35];p = 0.039), and hyponatremia (HR 0.90 [95% CI 0.82–0.99];p = 0.026) to each independently increase risk for death in COVID-19. We also found that neutrophilia (R = 0.2;p = 0.017), chemokine C-C motif ligand (CCL) 2 (R = 0.3;p = 0.043), and C-X-C motif chemokine ligand 9 (CXCL9) (R = 0.3;p = 0.050) were weakly but significantly correlated with mortality. Older age was associated with lower monocyte (R = –0.2;p = 0.006) and cluster of differentiation (CD) 16+ cell counts (R = –0.2;p = 0.002) and increased CCL11 concentration (R = 0.3;p = 0.050). Similarly, younger patients (< 65 yr) demonstrated a rise in CD4 (b-coefficient = 0.02;p = 0.036) and CD8 (0.01;p = 0.001) counts, as well as CCL20 (b-coefficient = 6.8;p = 0.036) during their ICU stay. This CD8 count rise was also associated with survival (b-coefficient = 0.01;p = 0.023). CONCLUSIONS: Age, comorbidities, and hyponatremia independently predict mortality in severe COVID-19. Neutrophilia and higher CCL2 and CXCL9 levels are also associated with higher mortality, while independent of age.

Psychotherapy and Follow-Up in Health Care Workers After the COVID-19 Epidemic: A Single Center's Experience.

Objective: The present study aims to analysis the mental health of high-risk health care workers (HHCWs) and low-risk HCWs (LHCWs) who were respectively exposed to COVID-19 wards and non-COVID-19 wards by following up on mental disorders in HCWs in China for 6 months. Methods: A multi-psychological assessment questionnaire was used to follow up on the psychological status of HCWs in the Affiliated Hospital of Xuzhou Medical University in Xuzhou City (a non-core epidemic area) at 6 months after the first evaluation conducted during the COVID-19 epidemic. Based on the risk of exposure to COVID-19 patients, the HCWs were divided into two groups: high-risk HCWs, who worked in COVID-19 wards, and low-risk HCWs, who worked in non-COVID-19 wards. Results: A total of 198 HCWs participated in the study, and 168 questionnaires were selected for evaluation. Among them, 93 (55.4%) were in the HHCW group and 75 (44.5%) were in the LHCW group. Significant differences were observed in salary, profession, and altruistic behavior between the two groups (P < 0.05). There were no significant differences in the anxiety, depression, insomnia, or posttraumatic stress disorder (PTSD) scores between the two groups. Logistic regression revealed that work stress was a major joint risk factor for mental disorders in HCWs. Among all the HCWs, a total of 58 voluntarily participated in psychotherapy; the analysis showed a significant decrease in anxiety, depression, PTSD, work stress, and work risk after attending psychotherapy. There were also significant differences in positive and negative coping styles before and after psychotherapy. Conclusion: In the present follow-up, work stress was the major contributing factor to mental disorders in HCWs. Psychotherapy is helpful in terms of stress management and should be provided to first-line COVID-19 HCWs.

Developing an AI-Based Learning System for L2 Learners' Authentic and Ubiquitous Learning in English Language

Motivated by the rapid development and application of artificial intelligence (AI) technologies in education and the needs of language learners during the COVID-19 pandemic, an AI-enabled English language learning (AIELL) system featuring authentic and ubiquitous learning for the acquisition of vocabulary and grammar in English as a second language (L2) was developed. The aim of this study was to present the developmental process and methods used to design, develop, evaluate, and validate the AIELL system and to distil key design features for English learning in authentic contexts. There were 20 participants in the tests, with three interviewees in the study. Mixed research methods were employed to analyse the data, including a demonstration test, a usability test, and an interview. The quantitative and qualitative data collected and analysed affirmed the validity and usability of the design and helped identify areas for further improvements to the desired features. This study informs the integration of AI into facilitating language teaching and learning guided by the mobile learning principle.

Analysis of Common Respiratory Infected Pathogens in 3100 Children after the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: To investigate the epidemiological features in children after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This study collected throat swabs and serum samples from hospitalized pediatric patients of Renmin Hospital of Wuhan University, Wuhan, Hubei province, China before and after the COVID-19 pandemic. Respiratory infected pathogens [adenovirus (ADV), influenza virus A/B (Flu A/B), parainfluenza virus 1/2/3 (PIV1/2/3), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and Chlamydia pneumoniae (CP)] were detected. The pathogens, age, and gender were used to analyze the epidemiological features in children after the COVID-19 pandemic. RESULTS: The pathogen detection rate was significantly higher in females than in males (P<0.05), and the infection of PIV1 and MP was mainly manifested. After the COVID-19 pandemic, PIV1, PIV3, RSV, and MP had statistically different detection rates among the age groups (P<0.05), and was mainly detected in patients aged 0-6 years, 0-3 years, 0-3 years, and 1-6 years, respectively. When comparing before the COVID-19 pandemic, the total detection rate of common respiratory pathogens was lower (P<0.05). Except for the increase in the detection rate of PIV1 and CP, the infection rate of other pathogens had almost decreased. CONCLUSION: The prevention and control measures for the COVID-19 pandemic effectively changed the epidemiological features of common respiratory tract infectious diseases in pediatric children.

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2.

There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study's aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.

Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates.

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.

Appetite loss, death anxiety and medical coping modes in COVID-19 patients: a cross-sectional study.

AIM: This study aims to explore the current level and associated factors of appetite and death anxiety amongst COVID-19 patients and also to identify correlation between the two variables. DESIGN: A cross-sectional study. METHODS: Demographic and characteristic questionnaires, templer death anxiety scale, council on nutrition of appetite questionnaire and medical coping modes questionnaire were utilized. RESULTS: The average scores of appetite and death anxiety were 19.46 (4.09) and 6.58, (3.21) respectively. 76 patients (100%) suffered from appetite loss, whilst 27 (35.50%) patients suffered from severe death anxiety. Marital status, COVID-19 disease condition ranks, educational level and death anxiety were explained 55.20% of the total variance in the appetite regression model (F = 31.83, p < .001), whilst the gender, avoidance coping strategy and appetite level were explained 49.80% of the total variance in death anxiety model (F = 17.80, p < .001). A moderate negative correlation between appetite and death anxiety was also confirmed (r=-.55, p < .001).

The effect of estrogen in coronavirus disease 2019.

The outcomes of coronavirus disease 2019 (COVID-19) vary between men and women. Some statistical reports have shown that men have a higher risk of developing COVID-19 and suffer from worse outcomes than females. Although there are many factors that can explain the high prevalence of COVID-19 in men, such as lifestyle habits and the different profile of comorbidities among sexes, the distinctions between male and female immune systems cannot be ignored. It has been sufficiently shown that sex differences have a critical influence on the shaping of immune response, which then leads to different pathogenesis in infectious diseases. Compared with males, females typically have a more effective innate and adaptive immune response to viral infections in COVID-19. What's more, there is a growing body of evidence showing that estrogen exerts an effect on the regulation of immune response. This article examines the effect and mechanism of estrogen on COVID-19.

The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression on the Incidence and Severity of COVID-19 Infection.

The novel coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented threat to the international community and raised major concerns in terms of public health safety. Although our current understanding of the complexity of COVID-19 pathogenesis remains limited, the infection is largely mediated by the interaction of viral spike protein and angiotensin-converting enzyme 2 (ACE2). The functional importance of ACE2 in different demographic and comorbid conditions may explain the significant variation in incidence and mortality of COVID-19 in vulnerable groups, and highlights its candidacy as a potential therapeutic target. We provide evidence supporting the idea that differences in incidence and severity of COVID-19 infection may be related to ACE2. Emerging data based on the prevalence and severity of COVID-19 among those with established high levels of ACE2 expression strongly support our hypothesis. Considering the burden of COVID-19 infection in these vulnerable groups and the impact of the potential therapeutic and preventive measures that would result from adopting ACE2-driven anti-viral strategies, our hypothesis may expedite global efforts to control the current COVID-19 pandemic.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension.

BACKGROUND: Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers (ACEIs/ARBs) had no harmful effects on coronavirus disease 2019 (COVID-19) patients complicated with hypertension. AIM: To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs. METHODS: All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study. Some patients switched from ACEIs/ARBs to calcium channel blocker (CCBs) after admission, while others continued using non-ACEIs/ARBs. We compared characteristics and clinical outcomes between these two groups of patients. RESULTS: A total of 53 patients were enrolled, 27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs. After controlling potential confounding factors using the Cox proportional hazards model, hospital stay was longer in patients who discontinued ACEIs/ARBs, with a hazard ratio of 0.424 (95% confidence interval: 0.187-0.962; P = 0.040), upon discharge than patients using other anti-hypertensive drugs. A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases [hazard ratio = 0.224 (95% confidence interval: 0.005-0.998; P = 0.0497)]. CONCLUSION: Patients in the discontinued ACEIs/ARBs group had longer hospital stays. Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

Decontamination of face masks with steam for mask reuse in fighting the pandemic COVID-19: Experimental supports.

The coronavirus disease 2019 pandemic caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has claimed many lives worldwide. Wearing medical masks (MMs) or N95 masks ([N95Ms] namely N95 respirators) can slow the virus spread and reduce the infection risk. Reuse of these masks can minimize waste, protect the environment, and help solve the current imminent shortage of masks. Disinfection of used masks is needed for their reuse with safety, but improper decontamination can damage the blocking structure of masks. In this study, we demonstrated using the avian coronavirus of infectious bronchitis virus to mimic SARS-CoV-2 that MMs and N95Ms retained their blocking efficacy even after being steamed on boiling water for 2 hours. We also demonstrated that three brands of MMs blocked over 99% viruses in aerosols. The avian coronavirus was completely inactivated after being steamed for 5 minutes. Altogether, this study suggested that MMs are adequate for use on most social occasions and both MMs and N95Ms can be reused for a few days with steam decontamination between use.

Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2.

The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.