Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

Heterologous chimpanzee adenovirus vector immunizations for SARS-CoV-2 spike and nucleocapsid protect hamsters against COVID-19.

Available COVID-19 vaccine only provide protection for a limited time due in part to the rapid emergence of viral variants with spike protein mutations, necessitating the generation of new vaccines to combat SARS-CoV-2. Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing early SARS-CoV-2 isolate spike (S) or nucleocapsid (N) proteins, the latter expressed as a fusion protein within herpes simplex virus glycoprotein D (gD), were tested individually or as a mixture in a hamster COVID-19 SARS-CoV-2 challenge model. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gD N fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable than the S protein may potentiate and prolong protection achieved by the currently used S protein based genetic COVID-19 vaccines.

Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications.

The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the 'gut-lung axis'. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.

Influence of empathy on work alienation among Chinese nurses during the COVID-19 pandemic: The mediating effect of ego depletion.

Background: Nurses' work alienation has become increasingly serious due to the increase in workload and risk during the coronavirus disease 2019 (COVID-19). However, no studies have investigated the link between empathy, ego depletion, and work alienation among Chinese nurses. The present study aimed to evaluate Chinese nurses' empathy, ego depletion, and work alienation and to examine whether nurses' ego depletion mediates the relationship between empathy and work alienation. Methods: This was a descriptive, cross-sectional study involving 353 nurses from Shaanxi. The Jefferson Scale of Empathy-Health Professionals, Self-Regulating Fatigue Scale and Work Alienation Questionnaire were used to collect data through an online survey. Structural equation modeling was conducted to analyze the mediating model. Results: Work alienation was negatively correlated with empathy (r = -0.305, p < 0.01) and positively correlated with ego depletion (r = 0.652, p < 0.01). Empathy was negatively correlated with ego depletion (r = -0.325, p < 0.01). Empathy can directly predict work alienation (ß = -0.263, p < 0.01), while ego depletion has a mediating effect between empathy and work alienation (ß = -0.309, p < 0.01), and the mediating effect accounts for 54.02% of the total effect. Conclusion: Nurses' work alienation was at a moderate-to-high level. Improving empathy can reduce work alienation through less ego depletion. Nursing managers should discover nurses' work alienation as soon as possible. Interventions to improve empathy can help replenish nurses' psychological resources, thereby reducing ego depletion and work alienation.

Epidemiological and clinical characteristics of respiratory syncytial virus and influenza infections in hospitalized children before and during the COVID-19 pandemic in Central China.

Background: Globally, the epidemiology of non-SARS-CoV-2 respiratory viruses like respiratory syncytial virus (RSV) and influenza virus was remarkably influenced by the implementation of non-pharmacological interventions (NPIs) during the COVID-19 pandemic. Our study explored the epidemiological and clinical characteristics of pediatric patients hospitalized with RSV or influenza infection before and during the pandemic after relaxation of NPIs in central China. Methods: This hospital-based prospective case-series study screened pediatric inpatients (age ≤ 14 years) enrolled with acute respiratory infections (ARI) for RSV or influenza infection from 2018 to 2021. The changes in positivity rates of viral detection, epidemiological, and clinical characteristics were analyzed and compared. Results: Median ages of all eligible ARI patients from 2018-2019 were younger than those from 2020-2021, so were ages of cases infected with RSV or influenza (RSV: 4.2 months vs. 7.2 months; influenza: 27.3 months vs. 37.0 months). Where the positivity rate for influenza was considerably decreased in 2020-2021 (1.4%, 27/1964) as compared with 2018-2019 (2.9%, 94/3275, P < 0.05), it was increased for RSV (11.4% [372/3275] vs. 13.3% [262/1964], P < 0.05) in the same period. The number of severe cases for both RSV and influenza infection were also decreased in 2020-2021 compared with 2018-2019. Conclusions: The implemented NPIs have had varied impacts on common respiratory viruses. A more effective prevention strategy for RSV infections in childhood is needed.

Epidemiological and clinical characteristics of respiratory syncytial virus and influenza infections in hospitalized children before and during the COVID‐19 pandemic in Central China

Background Globally, the epidemiology of non‐SARS‐CoV‐2 respiratory viruses like respiratory syncytial virus (RSV) and influenza virus was remarkably influenced by the implementation of non‐pharmacological interventions (NPIs) during the COVID‐19 pandemic. Our study explored the epidemiological and clinical characteristics of pediatric patients hospitalized with RSV or influenza infection before and during the pandemic after relaxation of NPIs in central China. Methods This hospital‐based prospective case‐series study screened pediatric inpatients (age ≤ 14 years) enrolled with acute respiratory infections (ARI) for RSV or influenza infection from 2018 to 2021. The changes in positivity rates of viral detection, epidemiological, and clinical characteristics were analyzed and compared. Results Median ages of all eligible ARI patients from 2018–2019 were younger than those from 2020–2021, so were ages of cases infected with RSV or influenza (RSV: 4.2 months vs. 7.2 months;influenza: 27.3 months vs. 37.0 months). Where the positivity rate for influenza was considerably decreased in 2020–2021 (1.4%, 27/1964) as compared with 2018–2019 (2.9%, 94/3275, P < 0.05), it was increased for RSV (11.4% [372/3275] vs. 13.3% [262/1964], P < 0.05) in the same period. The number of severe cases for both RSV and influenza infection were also decreased in 2020–2021 compared with 2018–2019. Conclusions The implemented NPIs have had varied impacts on common respiratory viruses. A more effective prevention strategy for RSV infections in childhood is needed.

Bibliometric and visualization analysis of research trend in mental health problems of children and adolescents during the COVID-19 pandemic.

Objectives: To analyze the evolution of research on children and adolescents mental health issues during COVID-19 pandemic and discuss research hotspots and cutting-edge developments. Methods: The literature obtained from the web of science core collection as of June 28, 2022, was analyzed using Citespace, VOSviewer bibliometric visualization mapping software. Results: A total of 6,039 relevant papers were found, of which 5,594 were included in the study. The number of literatures is growing since 2020; and the country, institution, and journal publications were analyzed. The co-citation analysis shows that there are more research articles among the highly cited articles and a lack of systematic reviews that use critical thinking for review. In the cluster analysis, mental health and life change were the most representative. The timeline view of the keywords shows that Online learning (#0), Public health (#1), and Mental health (#2) are the three largest clusters and shows the change over time. Conclusion: This study helped analyze the mental health of children and adolescents during the COVID-19 pandemic and identified hot trends and shortcomings, which are important references for the theoretical basis of future research and decision making and technical guidance for systematic reviews.

Multi-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome.

Our knowledge of the role of the gut microbiome in acute coronavirus disease 2019 (COVID-19) and post-acute COVID-19 is rapidly increasing, whereas little is known regarding the contribution of multi-kingdom microbiota and host-microbial interactions to COVID-19 severity and consequences. Herein, we perform an integrated analysis using 296 fecal metagenomes, 79 fecal metabolomics, viral load in 1378 respiratory tract samples, and clinical features of 133 COVID-19 patients prospectively followed for up to 6 months. Metagenomic-based clustering identifies two robust ecological clusters (hereafter referred to as Clusters 1 and 2), of which Cluster 1 is significantly associated with severe COVID-19 and the development of post-acute COVID-19 syndrome. Significant differences between clusters could be explained by both multi-kingdom ecological drivers (bacteria, fungi, and viruses) and host factors with a good predictive value and an area under the curve (AUC) of 0.98. A model combining host and microbial factors could predict the duration of respiratory viral shedding with 82.1% accuracy (error ± 3 days). These results highlight the potential utility of host phenotype and multi-kingdom microbiota profiling as a prognostic tool for patients with COVID-19.

Faecal microbiome-based machine learning for multi-class disease diagnosis.

Systemic characterisation of the human faecal microbiome provides the opportunity to develop non-invasive approaches in the diagnosis of a major human disease. However, shared microbial signatures across different diseases make accurate diagnosis challenging in single-disease models. Herein, we present a machine-learning multi-class model using faecal metagenomic dataset of 2,320 individuals with nine well-characterised phenotypes, including colorectal cancer, colorectal adenomas, Crohn's disease, ulcerative colitis, irritable bowel syndrome, obesity, cardiovascular disease, post-acute COVID-19 syndrome and healthy individuals. Our processed data covers 325 microbial species derived from 14.3 terabytes of sequence. The trained model achieves an area under the receiver operating characteristic curve (AUROC) of 0.90 to 0.99 (Interquartile range, IQR, 0.91-0.94) in predicting different diseases in the independent test set, with a sensitivity of 0.81 to 0.95 (IQR, 0.87-0.93) at a specificity of 0.76 to 0.98 (IQR 0.83-0.95). Metagenomic analysis from public datasets of 1,597 samples across different populations observes comparable predictions with AUROC of 0.69 to 0.91 (IQR 0.79-0.87). Correlation of the top 50 microbial species with disease phenotypes identifies 363 significant associations (FDR < 0.05). This microbiome-based multi-disease model has potential clinical application in disease diagnostics and treatment response monitoring and warrants further exploration.

Antibiotics and probiotics impact gut antimicrobial resistance gene reservoir in COVID-19 patients.

Dysbiosis of gut microbiota is well-described in patients with coronavirus 2019 (COVID-19), but the dynamics of antimicrobial resistance genes (ARGs) reservoir, known as resistome, is less known. Here, we performed longitudinal fecal metagenomic profiling of 142 patients with COVID-19, characterized the dynamics of resistome from diagnosis to 6 months after viral clearance, and reported the impact of antibiotics or probiotics on the ARGs reservoir. Antibiotic-naive patients with COVID-19 showed increased abundance and types, and higher prevalence of ARGs compared with non-COVID-19 controls at baseline. Expansion in resistome was mainly driven by tetracycline, vancomycin, and multidrug-resistant genes and persisted for at least 6 months after clearance of SARS-CoV-2. Patients with expanded resistome exhibited increased prevalence of Klebsiella sp. and post-acute COVID-19 syndrome. Antibiotic treatment resulted in further increased abundance of ARGs whilst oral probiotics (synbiotic formula, SIM01) significantly reduced the ARGs reservoir in the gut microbiota of COVID-19 patients during the acute infection and recovery phase. Collectively, these findings shed new insights on the dynamic of ARGs reservoir in COVID-19 patients and the potential role of microbiota-directed therapies in reducing the burden of accumulated ARGs.

Compliance with Health Recommendations and Vaccine Hesitancy During the COVID Pandemic in Nine Countries.

Longitudinal data from the Parenting Across Cultures study of children, mothers, and fathers in 12 cultural groups in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the USA; N = 1331 families) were used to understand predictors of compliance with COVID-19 mitigation strategies and vaccine hesitancy. Confidence in government responses to the COVID pandemic was also examined as a potential moderator of links between pre-COVID risk factors and compliance with COVID mitigation strategies and vaccine hesitancy. Greater confidence in government responses to the COVID pandemic was associated with greater compliance with COVID mitigation strategies and less vaccine hesitancy across cultures and reporters. Pre-COVID financial strain and family stress were less consistent predictors of compliance with COVID mitigation strategies and vaccine hesitancy than confidence in government responses to the pandemic. Findings suggest the importance of bolstering confidence in government responses to future human ecosystem disruptions, perhaps through consistent, clear, non-partisan messaging and transparency in acknowledging limitations and admitting mistakes to inspire compliance with government and public health recommendations.

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling.

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as ß-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher ß-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, ß-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.

Adolescent Positivity and Future Orientation, Parental Psychological Control, and Young Adult Internalising Behaviours during COVID-19 in Nine Countries.

The COVID-19 pandemic disrupted many young adults' lives educationally, economically, and personally. This study investigated associations between COVID-19-related disruption and perception of increases in internalising symptoms among young adults and whether these associations were moderated by earlier measures of adolescent positivity and future orientation and parental psychological control. Participants included 1329 adolescents at Time 1, and 810 of those participants as young adults (M age = 20, 50.4% female) at Time 2 from 9 countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). Drawing from a larger longitudinal study of adolescent risk taking and young adult competence, this study controlled for earlier levels of internalising symptoms during adolescence in examining these associations. Higher levels of adolescent positivity and future orientation as well as parent psychological control during late adolescence helped protect young adults from sharper perceived increases in anxiety and depression during the first nine months of widespread pandemic lockdowns in all nine countries. Findings are discussed in terms of how families in the 21st century can foster greater resilience during and after adolescence when faced with community-wide stressors, and the results provide new information about how psychological control may play a protective role during times of significant community-wide threats to personal health and welfare.

USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.

Pre-pandemic psychological and behavioral predictors of responses to the COVID-19 pandemic in nine countries.

Prior to the COVID-19 pandemic, adolescents (N = 1,330; Mages = 15 and 16; 50% female), mothers, and fathers from nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, United States) reported on adolescents' internalizing and externalizing problems, adolescents completed a lab-based task to assess tendency for risk-taking, and adolescents reported on their well-being. During the pandemic, participants (Mage = 20) reported on changes in their internalizing, externalizing, and substance use compared to before the pandemic. Across countries, adolescents' internalizing problems pre-pandemic predicted increased internalizing during the pandemic, and poorer well-being pre-pandemic predicted increased externalizing and substance use during the pandemic. Other relations varied across countries, and some were moderated by confidence in the government's handling of the pandemic, gender, and parents' education.

Corrigendum: Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients.

[This corrects the article DOI: 10.3389/fimmu.2021.686240.].