RAPID IDENTIFICATION OF ETIOLOGICAL AGENTS OF RESPIRATORY TRACT INFECTIONS DURING THE COVID-19 PANDEMIC USING THE MULTIPLEX-PCR METHOD.

Objective. Most respiratory infections have similar symptoms, so it is clinically difficult to determine their etiology. This study aimed to show the importance of molecular diagnostics in identifying the etiological agent of respiratory infections, especially during the coronavirus disease 2019 (COVID-19) pandemic. Methods. A total of 849 samples from patients hospitalized at the University Clinical Center Kragujevac (from January 1 to August 1, 2022) were examined using automated multiplex-polymerase chain reaction (PCR) tests. The BioFire-FilmArray-Respiratory Panel 2.1 test was used for 742 nasopharyngeal swabs [identification of 19 viruses (including SARS-CoV-2) and four bacteria], while the BioFire-FilmArray-Pneumonia Panel was used [identification of 18 bacteria and nine viruses] (BioMerieux, Marcy l'Etoile, France) for 107 tracheal aspirates. The tests were performed according to the manufacturer's instructions, and the results were available within an hour. Results. In 582 (78.4%) samples, the BioFire-FilmArray-Respiratory Panel 2.1 plus test identified at least one pathogen. The rhinovirus (20.6%), SARS-CoV-2 (17.7%), influenza A (17.5%), respiratory syncytial virus (12.4%), and parainfluenza 3 (10.1%) were the most common. Other viruses were found less frequently, and Bordetella parapertussis was detected in one sample. In 85 (79.4%) samples, the BioFire-FilmArray-Pneumonia Panel test identified at least one bacterium or virus. The most prevalent bacteria were Staphylococcus aureus (42.4%), Haemophilus influenzae (41.2%), Streptococcus pneumoniae (36.5%), Moraxella catarrhalis (22.3%), and Legionella pneumophila (2.4%). Among viruses, rhinovirus (36.5%), adenovirus (23.5%), influenza A (11.8%), and the genus Coronavirus (4.7%), were detected. Conclusion. Multiplex-PCR tests improved the implementation of therapeutic and epidemiological measures, preventing the spread of the COVID-19 infection and Legionnaires' disease.Copyright © 2022, Serbian Medical Society. All rights reserved.

Immunopathological mechanisms in sepsis of viral etiology in COVID-19.

The article provides information on immunopathology in sepsis and the commonality between immunopathogenetic processes of sepsis and the new coronavirus infection (COVID-19). As a result of the inability of the immune system to cope with aggression of the pathogen, inadequate immune activity occurs manifested by the systemic inflammatory response syndrome, resulting in damage to tissues of the host organism. In response, compensatory anti-inflammatory response syndrome is activated, which is manifested by inhibition of the immune response. One of its main mechanisms is signals produced by membrane receptors and their ligands. Against the background of inability of the host organism to neutralise the pathogen, numerous pathological phenomena and complications occur leading to damage to human tissues.Copyright © 2021, Krasnoyarsk State Medical University. All rights reserved.

Features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2.

Objective To summarize and analyze the features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). Methods In this study,an analysis was performed for the liver function test results of the locally transmitted or imported pediatric patients with SARS - CoV - 2 infection during isolation who were admitted to Guangzhou Eighth People's Hospital,Guangzhou Medical University,since May 21,2021,and the clinical data and the constituent ratio of liver injury were compared between the pediatric patients infected with Delta variant and those infected with Omicron variant. The independent samples t - test or the Mann - Whitney U test was used for comparison of continuous data between two groups,and the chi - square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results A total of 85 pediatric patients infected with SARS - CoV - 2 were enrolled,among whom there were 32 (37. 6%)pediatric patients infected with Delta variant and 53 (62. 4%)pediatric patients infected with Omicron variant,and there were no significant differences between the two groups in age,sex, body height,body weight,and comorbidities (all P > 0. 05). There were no significant differences between the two groups in alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma - glutamyl transpeptidase,total bilirubin,albumin,and cholinesterase (all P > 0. 05),and the pediatric patients infected with Omicron variant had a significantly higher level of total bile acid (TBA)than those infected with Delta variant (Z = - 2. 336,P = 0. 020). However,the median values of TBA were within the normal range and the ratios of abnormal TBA were no significant difference between the two groups (P > 0. 05). Among the 85 pediatric patients,10 (11. 8%)had a mild increase in liver function parameters,among whom 7 had an increase in TBA,1 had an increase in ALT, 1 had increases in ALT and AST,and 1 had an increase in ALP. The analysis of liver injury in the pediatric patients infected with Delta variant or Omicron variant showed that there was no significant difference in the constituent ratio of liver injury caused by the two variants (6. 3% vs 15. 1%,chi2 = 0. 691,P = 0. 406). Conclusion Mild liver injury is observed in pediatric patients infected with Delta and Omicron variants of SARS - CoV - 2,but further studies are needed to evaluate the long - term influence of such infection on liver function.Copyright © 2022 Editorial Board of Jilin University

A Dynamic-Static Dual Input Deep Neural Network Algorithm for Diagnosing COVID-19 by Cough

The COVID-19 (corona virus disease 2019) has caused serious impacts worldwide. Many scholars have done a lot of research on the prevention and control of the epidemic. The diagnosis of COVID-19 by cough is non-contact, low-cost, and easy-access, however, such research is still relatively scarce in China. Mel frequency cepstral coefficients (MFCC) feature can only represent the static sound feature, while the first-order differential MFCC feature can also reflect the dynamic feature of sound. In order to better prevent and treat COVID-19, the paper proposes a dynamic-static dual input deep neural network algorithm for diagnosing COVID-19 by cough. Based on Coswara dataset, cough audio is clipped, MFCC and first-order differential MFCC features are extracted, and a dynamic and static feature dual-input neural network model is trained. The model adopts a statistic pooling layer so that different length of MFCC features can be input. The experiment results show the proposed algorithm can significantly improve the recognition accuracy, recall rate, specificity, and F1-score compared with the existing models. © 2023 Chinese Institute of Electronics. All rights reserved.

Traditional Chinese Medicine Syndrome Differentiation of Delta and Omicron Variants of SARS-CoV-2 Carriers in Changsha,Hunan.

Objective: To summarize and compare the main traditional Chinese medicineTCMsyndromes of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2SARS-CoV-2 carriers to provide references for the syndrome evolution and syndrome differentiation of SARS-CoV-2 infection. Method(s):The TCM medical records of imported and local cases of infection with Delta and Omicron variants of SARS-CoV-2 in Changsha since September 23,2021 to March 27,2022 were collected,including 18 Delta variant cases and 36 Omicron variant cases. Their TCM diagnosis information and TCM pathogenesis were analyzed and compared. Result(s): The common manifestations in Delta variant cases were cough,fever,chest distress/shortness of breath,sore muscles,nausea,dry mouth,dry or sore throat,thick and greasy tongue coating,and rapid and slippery pulse. The predominant pathogenesis was dampness-heat in the upper-energizer and heat stagnation in the lesser Yang combined with dampness. The occurrence of chest distress/shortness of breath,greasy tongue coating,slippery pulse,and the proportion of dampness-heat in the upper-energizer syndrome were higher in Delta variant cases than in Omicron variant cases P<0.05. The common manifestations in Omicron variant cases were itchy and sore throat,nasal congestion,running nose,fever,mild aversion to cold,dry mouth,dizziness,slightly reddish tongue with thin white coating,and rapid or wiry pulse. The predominant pathogenesis was wind-dryness invading defensive exterior,and heat stagnation in the lesser Yang. The occurrence of white-coated tongue and the proportion of wind-dryness invading defensive exterior syndrome were higher in Omicron variant cases than in Delta variant casesP<0.05. Conclusion(s): There are certain differences in TCM syndromes and the corresponding pathogenesis between Delta variant and Omicron variant cases in Changsha,Hunan. The Delta variant of SARS-COV-2 tends to induce dampness-heat syndrome, whereas Omicron variant infection tends to elicit wind-dampness syndrome,which is expected to provide a reference for the pathogenesis evolution of SARS-COV-2 infection.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Analysis of pathogen detection results of upper respiratory tract specimens from fever clinic patients

Objective: To explore the pathogen composition and distribution characteristics of pathogens in respiratory samples from patients with fever of unknown origin. Methods: A total of 96 respiratory samples of patients with unknown cause fever with respiratory symptoms were collected from four hospitals above grade II in Shijiazhuang area (Hebei Provincial Hospital of Traditional Chinese Medicine, Luancheng District People's Hospital, Luquan District People's Hospital, Shenze County Hospital) from January to April 2020, and multiplex-fluorescent polymerase chain reaction(PCR)was used to detect influenza A virus, influenza B virus, enterovirus, parainfluenza virus I/II/III/IV, respiratory adenovirus, human metapneumovirus, respiratory syncytial virus, human rhinovirus, human bocavirus, COVID-19, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Streptococcus pneumoniae, Klebsiella pneumoniae, Group A streptococcus, Haemophilus influenzae, Staphylococcus aureus nucleic acid detection, the results were analyzed for chi-square. Results: A total of 8 pathogens were detected in the upper respiratory tract samples of 96 fever patients, including 1 kind of virus, 6 kinds of bacterias, and Mycoplasma pneumoniae. There were 12 viruses including influenza virus and parainfluenza virus, Legionella pneumophila and Chlamydia pneumoniae were not detected. The pathogen detection rates in descending order were Streptococcus pneumoniae (58/96, 60.42%), Haemophilus influenzae(38/96, 39.58%), Klebsiella pneumoniae (14/96, 14.58%), Staphylococcus aureus (10/96, 10.42%), Mycoplasma pneumoniae (8/96, 8.33%), Pseudomonas aeruginosa (6/96, 6.25%), Group A streptococcus (4/96, 4.17%) and human rhinovirus (2/96, 2.08%). The proportions of single-pathogen infection and multi-pathogen mixed infection in fever clinic patients were similar, 41.67% (40/96) and 45.83% (44/96), respectively, and 12.50% (12/96)of the cases had no pathogens detected. The infection rate of Mycoplasma pneumoniae in female patients with fever (21.43%) was higher than that in male patients with fever (2.94%) (P < 0.05). There was no statistical difference between the distribution of of other pathogens and gender and age(P > 0.05). Conclusions: The upper respiratory tract pathogens were mainly bacterial infections, and occasional human rhinovirus and Mycoplasma pneumonia infections. In clinical diagnosis and treatment, comprehensive consideration should be given to the pathogen detection.

A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Repurposing of poly-gamma-glutamic acid, immunotherapeutic drug for cervical intraepithelial neoplasia 1, as covid-19 treatment

Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.

Optimizing mRNA vaccines and virusmediated CAR T-cell therapy for immuno-oncology: Synthetic tools for gene modification

With the success of mRNA vaccines during the COVID-19 pandemic and CAR T-cell therapies in clinical trials, there is growing opportunity for immunotherapies in the treatment of many types of cancers. Lentiviral vectors have proven effective at delivery of genetic material or gene editing technology for ex vivo processing, but the benefits and promise of Adeno-associated virus (AAV) and mRNA tools for in vivo immunotherapy have garnered recent interest. Here we describe complete synthetic solutions for immuno-oncology research programs using either mRNA-vaccines or virus-mediated cell and gene engineering. These solutions optimize workflows to minimize screening time while maximizing successful research results through: (1) Efficiency in lentiviral packaging with versatility in titer options for high-quality particles. (2) A highthroughput viral packaging process to enable rapid downstream screening. (3) Proprietary plasmid synthesis and preparation techniques to maintain ITR integrity through AAV packaging and improve gene delivery. (4) Rapid synthesis, in vitro transcription, and novel sequencing of mRNA constructs for complete characterization of critical components such as the polyA tail. The reported research demonstrates a streamlined approach that improves data quality through innovative synthesis and sequencing methodologies as compared to current standard practices.

Clinical Characteristics of Patients with Sars-Cov-2 Omicron Variant and COVID-19 Vaccination with Clinical Outcome Findings in Shanghai, China: A Single Center, Retrospective, Observational Study

Objectives: This study aimed to determine disease severity, clinical features, clinical outcome in hospitalized patients with the Omicron variant and evaluate the effectiveness of one-dose, two-dose, and three-dose inactivated vaccines in reducing viral loads, disease course, ICU admissions and severe diseases. Method(s): Retrospective cohort analysis was performed on 5,170 adult patients (>=18 years) identified as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction admitted at Shanghai Medical Center for Gerontology between March 2022 and June 2022. COVID-19 vaccination effectiveness was assessed using logistic regression models evaluating the association between the risk of vaccination and clinical outcomes, adjusting for confounders. Result(s): Among 5,170 enrolled patients, the median age was 53 years, and 2,861 (55.3%) were male. 71.0% were mild COVID-19 cases, and cough (1,137 [22.0%]), fever (592 [11.5%]), sore throat (510 [9.9%]), and fatigue (334 [6.5%]) were the most common symptoms on the patient's first admission. Ct values increased generally over time and 27.1% patients experienced a high viral load (Ct value< 20) during their stay. 105(2.0%) of these patients were transferred to the intensive care unit after admission. 97.1% patients were cured or showed an improvement in symptoms and 0.9% died in hospital. The median length of hospital stay was 8.7+/-4.5 days. In multivariate logistic analysis, booster vaccination can significantly reduce ICU admissions and decrease the severity of COVID-19 outcome when compared with less doses of vaccine (OR=0.75, 95%CI, 0.62-0.91, P<=0.005;OR=0.99, 95%CI, 0.99-1.00, p<0.001). Conclusion(s): In summary, the most of patients who contracted SARSCoV-2 omicron variant had mild clinical features and patients with vaccination took less time to lower viral loads. As the COVID-19 pandemic progressed, an older and less vaccinated population was associated with higher risk for ICU admission and severe disease.Copyright © 2023

Analysis of avian disease transmission risk and prevention measures in China

Many zoonotic diseases are found in wild animals and present a serious risk to human health, in particularly the virus carried by birds flying freely around the world is hard to control. There are three main bird migration routes which cover the most areas of China. It is important to investigate and fully understand the types of avian transmitted diseases in key areas on the bird migration routines and its impacts on both birds and human health. However, no literature is available in how about the risk of virus carried by migrating birds, and how to predict and reduce this risk of virus spreading to human being so far. In this paper, we first reviewed the main pathogen types carried by birds, including coronaviruses, influenza viruses, parasites, Newcastle disease virus (NDV), etc., and then discussed the spread risk of avian viruses to human being and animals in key areas of biosafety prevention. We also analyzed and discussed the risk of cross-spread of diseases among different bird species in nature reserves located on bird migration routes which provide sufficient food sources for migratory birds and attract numerous birds. Diseases transmitted by wild birds pose a serious threat to poultry farms, where high density of poultry may become avian influenza virus (AIV) reservoirs, cause a risk of avian influenza outbreaks. Airports are mostly built in suburban areas or remote areas with good ecological environment. There are important transit places for bird migration and densely populated areas, which have serious risk of disease transmission. Finally, this paper puts forward the following prevention suggestions from three aspects. First, establish and improve the monitoring and prediction mechanism of migratory birds, and use laser technology to prevent contact between wild birds and poultry. Second, examine and identify virus types carried by birds in their habitats and carry out vaccination. Third, protect the ecological environment of bird habitat, and keep wild birds in their natural habitat, so as to reduce the contact between wild birds and human and poultry, and thus reduce the risk of virus transmission.

Research progress of antiviral material basis and mechanism of Compound Qinlan Oral Liquid.

Compound Qinlan Oral Liquid (,CQOL) is derived from Yinqiao San (), which is composed of Jinyinhua (Lonicerae Japonicae Flos), Huangqin (Scutellariae Radix), Lianqiao (Forsythiae Fructus) and Banlangen (Isatidis Radix). It is a common clinical herbal medicine for clearing heat and detoxification, and has antiviral effects. By reviewing the active ingredients of CQOL and the research progress on its anti-influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy, with view to providing a basis for the clinical use of CQOL in treatment of respiratory diseases caused by SARS-CoV-2.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

The SARS-CoV-2 Antibody and Drug Research Based on the Structure of the Spike Protein and the Mechanism of Cell Entry.

COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV- 2.COVID-19 is now a pandemic, and is not yet fully under control.As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission.The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVII)-19.Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1 ) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2) , the specific receptor of SARS-CoV-2, is introduced in detail.Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV- 2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary.(2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways.With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2) , lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane.(3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type.(4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied.Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment.Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.Copyright © Palaeogeography (Chinese Edition).All right reserved.

Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.

Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO: A retrospective single-center experience

Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.

Anxiety and depression among epilepsy patients in low-risk areas for COVID-19 in the northern part of Guizhou Province, China, during the COVID-19 pandemic

BackgroundThis study was aimed to investigate whether patients with epilepsy (PWE) have higher depression and anxiety levels than the normal population in low-risk areas for coronavirus disease 2019 (COVID-19) in the northern part of Guizhou Province, China, during the COVID-19 epidemic, to evaluate their knowledge on COVID-19, and to analyze related factors for the psychological distress of PWE at this special time.MethodsThe survey was conducted online from February 28, 2020 to March 7, 2020 via a questionnaire. PWE from the outpatient clinic of epilepsy of the Affiliated Hospital of Zunyi Medical University, and healthy people matched for age and sex, participated in this study. Mental health was assessed via a generalized anxiety self-rating scale (GAD-7) and the self-rating depression scale (PHQ-9). The knowledge of COVID-19 in both groups was investigated.ResultsThere were no significant differences in the general demographics between the PWE and healthy control groups. The scores of PHQ-9 (P < 0.01) and GAD-7 (P < 0.001) were higher in the PWE group than in the healthy group. There was a significant difference in the proportions of respondents with different severities of depression and anxiety, between the two groups, which revealed significantly higher degree of depression and anxiety in PWE than in healthy people (P = 0, P = 0). Overwhelming awareness and stressful concerns for the pandemic and female patients with epilepsy were key factors that affect the level of anxiety and depression in PWE. Further, the PWE had less accurate knowledge of COVID-19 than healthy people (P < 0.001). There was no statistically significant difference between the two groups in the knowledge of virus transmission route, incubation period, susceptible population, transmission speed, clinical characteristics, and isolation measures on COVID-19 (P > 0.05). PWE knew less about some of the prevention and control measures of COVID-19 than healthy people.ConclusionsDuring the COVID-19 epidemic, excessive attention to the epidemic and the female sex are factors associated with anxiety and depression in PWE, even in low-risk areas.

Expressions of miR-21 TGF-beta/Smad signaling pathway in peripheral blood of bronchial asthma patients complicated with respiratory virus infection

OBJECTIVE: To investigate the expressions of peripheral blood microRNA-21(miR-21) and transforming growth factor-beta(TNF-beta)/Smad signaling transduction pathway in patients with bronchial asthma complicated with respiratory virus infection. METHODS: Totally 109 patients with asthma complicated with respiratory virus infection(study group) and 104 patients without virus infection(control group) in the Third People's Hospital of Gansu Province between Feb.2019 and Feb.2021 were selected for the cross-sectional study. The basic data of the two groups were collected, and parameters including vital signs, lung function, peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins were measured. According to the guidelines, the patients of the two groups were divided into acute exacerbation phase and stable phase. The examination results of each group were compared and the levels of peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins expression of patients with asthma complicated with respiratory virus infection were analyzed. RESULTS: In study group, the proportion of respiratory virus infection among 109 patients was 33.94% for influenza virus, 23.85% for human rhinovirus, 19.27% for respiratory syncytial virus, 10.09% for parainfluenza virus, 6.42% for adenovirus, 4.59% for human coronavirus and 1.83% for human metapneumovirus respectively. The proportion of patients with acute exacerbation phase in the study group was higher than that in the control group, and the levels of peripheral blood miR-21, TGF-beta1, Smad7, pSmad2 and pSmad3 were higher than those in control group(P<0.05). The levels of miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 in peripheral blood of patients with acute exacerbation phase of asthma were higher than those of patients with stable phase of asthma(P<0.05). There were no statistical differences in peripheral blood miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 levels in asthma patients with different virus infections. CONCLUSION: Early respiratory virus infections might lead to increased expression of peripheral blood miR-21 and increased activation of TGF-beta/Smad signaling pathway in patients with asthma, which played an important role in acute attack of asthma.

Characterization of Adaptive Immune Responses to SARS-CoV-2 Updated Bivalent Booster

Bivalent COVID-19 vaccines that contain two mRNAs encoding Wuhan-1 and Omicron BA.4/5 spike proteins are successful in preventing infection from the original strain and Omicron variants, but the quality of adaptive immune responses is still not well documented. This study aims at characterizing adaptive immune responses to the bivalent booster vaccination in 46 healthy participants. Plasma and PBMC were collected prior and three weeks after bivalent booster. We measured anti-N, anti-S, and RBD IgM, IgA, IgG plasma titers against original, Omicron BA.1, and BA.5 variants (pending) as well as total anti-S IgG titers and surrogate Virus Neutralization capacity against the Alpha, Delta, and BA.1 variant. With spectral flow-cytometry we identified peripheral blood B-cells specific for the RBD of the S-protein of the original and BA.1 variants. T-cell-specific responses were assessed by cytokine release assay after stimulation with SARS-CoV-2 peptides from the original, BA.1, BA.4, and BA.5 variants (pending). Finally, we performed TRB and IGH repertoire studies on sorted CD4+, CD8+, CD19+ lymphocytes, to study breadth of SARS-CoV-2 specific clonotypes (pending). 27/46 participants were analyzed;9 had SARS-CoV-2 infection (COVID+), while 18 are infection naive (COVID-). In both groups, median time since last dose of SARS-CoV-2 vaccine (3rd or 4th) was 11 months. All subjects were positive for anti-S IgG prior to bivalent booster. The COVID + group displayed anti-S IgG pre-booster levels and neutralization against BA.1 higher than the COVID- group. Significant increase post-boost of total anti-S IgG and BA.1 neutralizing activity was detected in the COVID- but not in the COVID+ group;however, no difference in neutralization activity post-boost was detected between the two groups. Furthermore, the COVIDgroup showed significant increase in the frequency of CD19+ and CD27+ switched memory B-cells specific for BA.1 RBD in post-boost compared to pre-boost samples. However, post-boost frequencies of the same B-cells were higher in the COVID+ compared to the COVID- group. These preliminary findings confirm that among individual immunized with the original COVID-19 mRNAvaccine, prior COVID infection provides increased protection against SARS-CoV-2 variants. They also demonstrate that booster immunization with the bivalent vaccine induces robust adaptive immune responses against Omicron variant.[Formula presented][Formula presented]Copyright © 2023 Elsevier Inc.

Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.