Extrafollicular IgD-CD27-CXCR5-CD11c- DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19.

Although therapeutic B cell depletion dramatically resolves inflammation in many diseases in which antibodies appear not to play a central role, distinct extrafollicular pathogenic B cell subsets that accumulate in disease lesions have hitherto not been identified. The circulating immunoglobulin D (IgD)-CD27-CXCR5-CD11c+ DN2 B cell subset has been previously studied in some autoimmune diseases. A distinct IgD-CD27-CXCR5-CD11c- DN3 B cell subset accumulates in the blood both in IgG4-related disease, an autoimmune disease in which inflammation and fibrosis can be reversed by B cell depletion, and in severe COVID-19. These DN3 B cells prominently accumulate in the end organs of IgG4-related disease and in lung lesions in COVID-19, and double-negative B cells prominently cluster with CD4+ T cells in these lesions. Extrafollicular DN3 B cells may participate in tissue inflammation and fibrosis in autoimmune fibrotic diseases, as well as in COVID-19.

The Impact of mNGS Technology in the Etiological Diagnosis of Severe Pneumonia in Children During the Epidemic of COVID-19.

Purpose: Metagenomic next-generation sequencing (mNGS) is an emerging technique for pathogen detection. However, most literature on the clinical application of pediatrics generally comprises case reports or small-scale cohort studies. Patients and Methods: A total of 101 children with community-acquired severe pneumonia admitted to Tianjin Children's Hospital from November 2021 to February 2022 were included. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS. The performances of mNGS and conventional tests on pulmonary infection diagnosis and pathogen identification were compared. Results: According to our data, mNGS had a broader spectrum for pathogen detection. The mNGS results of BALF showed that the number of children with severe pneumonia hospitalized for mycoplasma pneumoniae infection was more than that for other bacterial infections during the COVID-19 epidemic. In addition, 43 cases (42.6%) had been identified with mixed infection, including 36 cases (35.6%) of Mycoplasma pneumoniae mixed with other pathogenic bacteria. Analytically, the mNGS exhibited significantly enhanced detection in the BALF as compared with the conventional laboratory pathogenic detection approaches (P < 0.05). The Pearson correlation analysis revealed positive correlation between the time of fever during hospitalization and the number of mycoplasma sequences (P < 0.05). Conclusion: Compared with traditional methods, mNGS has a higher etiological detection rate and can comprehensively detect various pathogens of severe pneumonia. Therefore, mNGS of bronchoalveolar lavage fluid should be performed in children with severe pneumonia, which is of great significance for guiding treatment.

Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model.

BACKGROUND: Porcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days. RESULTS: The synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. CONCLUSIONS: The synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

[Analysis of age-based stratified renal involvement in Tianjin first batch of 430 patients with Omicron variant of novel coronavirus infection].

OBJECTIVE: To investigate the incidence and clinical characteristics of renal involvement with Omicron coronavirus infection in age-based stratified patients. METHODS: The first batch of 430 convalescent patients with Omicron coronavirus treated in Tianjin First Central Hospital from January 21, 2022 to March 7, 2022 were enrolled in this study. The baseline information, vaccination status and laboratory examination information of patients were extracted in order to analyze the incidence of renal involvement in age-based stratified patients. Multivariate Logistic regression analysis was conducted to determine the risk factors of renal involvement in different age groups. RESULTS: Excluding those younger than 1 year old and those with a history of chronic kidney disease, a total of 421 patients were included. There were 184 males and 237 females with an average age of (36.65±21.28) years. The types of renal involvement included pathological tubular urine (28.9%), proteinuria (16.9%), renal hematuria (14.7%), a slight decrease of estimated glomerular filtration rate (eGFR, 9.3%), renal glycosuria (0.5%). According to their age, all patients were divided into three groups: 113 cases of ≤ 18 years old, 244 cases of 19-59 years old and 64 cases of ≥ 60 years old. Significant difference was founded in the incidence of renal involvement among the three groups. The incidence of proteinuria, pathological tubular urine and slight decline of eGFR in the ≥ 60 years old group were significantly higher than those in the ≤ 18 years old group [28.1% (18/64) vs. 8.0% (9/112), 42.2% (27/64) vs. 19.6% (22/112), 34.9% (22/63) vs. 6.2% (7/113), respectively, all P < 0.01]. The incidence of slight decline of eGFR was significantly higher than that in 19-59 years old group [34.9% (22/63) vs. 4.1% (10/243), P < 0.01]. Multivariate Logistic regression analysis showed that age was significantly correlated with renal involvement after adjusting for the baseline situation, serological indexes and Omicron infection related indexes [odds ratio (OR) = 1.059, 95% confidence interval (95%CI) was 1.021-1.097, P = 0.002]. Compared with the group ≤ 18 years old, the risk of renal involvement in the group ≥ 60 years old was significantly increased (OR = 26.245, 95%CI was 1.357-507.458, P = 0.031). Age ≥ 60 years old was an independent risk factor for renal involvement with Omicron coronavirus infection. CONCLUSIONS: Although a low incidence of severe cases in Tianjin first batch of 430 patients with Omicron coronavirus infection, there is still a high incidence of renal involvement. Advanced age is the risk factor of renal involvement. We should pay more attention to the renal involvement of elderly with Omicron coronavirus infection.

Epidemiological characteristics of COVID-19 cases in Xianyang, Shaanxi

Objective: To analyze the epidemiological characteristics of COVID-19 cases reported in Xianyang City from January to February 2020.

Adrenal tropism of SARS-CoV-2 and adrenal findings in a post-mortem case series of patients with severe fatal COVID-19.

Progressive respiratory failure and hyperinflammatory response is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. Despite mounting evidence of disruption of the hypothalamus-pituitary-adrenal axis in COVID-19, relatively little is known about the tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to adrenal glands and associated changes. Here we demonstrate adrenal viral tropism and replication in COVID-19 patients. Adrenal glands showed inflammation accompanied by inflammatory cell death. Histopathologic analysis revealed widespread microthrombosis and severe adrenal injury. In addition, activation of the glycerophospholipid metabolism and reduction of cortisone intensities were characteristic for COVID-19 specimens. In conclusion, our autopsy series suggests that SARS-CoV-2 facilitates the induction of adrenalitis. Given the central role of adrenal glands in immunoregulation and taking into account the significant adrenal injury observed, monitoring of developing adrenal insufficiency might be essential in acute SARS-CoV-2 infection and during recovery.

Determinants of COVID-19 testing among late middle-aged and older adults: Applying the health belief model.

Objectives: The purpose of this study was to examine correlates of taking a COVID-19 test among late middle-aged and older adults using nationally representative data. Methods: Data were obtained from the 2020 Health and Retirement Study midway release COVID-19 module. Our sample was representative of community residing adults aged 51 and over in the United States (n = 2,870). Measurements: We regressed taking a COVID-19 test on demographic characteristics, medical comorbidities, and measures related to the health belief model (i.e., perceived severity, perceived susceptibility, cues to action, and perceived barriers) using logistic regression, stratifying the model by 10-year age categories. Results: Concern about the pandemic was associated with an increase in the likelihood of taking a test among late middle-aged adults. Knowing someone who was diagnosed with COVID-19 was associated with taking a test in most age categories. Financial barriers and knowing someone who died of COVID-19 were not associated with taking a test. Conclusions: How late middle-aged and older adults perceive the COVID-19 pandemic may significantly influence their likelihood of taking a COVID-19 test.

Review on visualization technology in simulation training system for major natural disasters

Major natural disasters have occurred frequently in the last few years, resulting in increased loss of life and economic damage. Most emergency responders do not have first-hand experience with major natural disasters, and thus, there is an urgent need for pre-disaster training. Due to the scenes unreality of traditional emergency drills, the failure to appeal to the target audience and the novel coronavirus pandemic, people are forced to maintain safe social distancing. Therefore, it is difficult to carry out transregional or transnational emergency drills in many countries under the lockdown. There is an increasing demand for simulation training systems that use virtual reality, augmented reality, and mixed reality visualization technologies to simulate major natural disasters. The simulation training system related to natural disasters provides a new way for popular emergency avoidance science education and emergency rescue personnel to master work responsibilities and improve emergency response capabilities. However, to our knowledge, there is no overview of the simulation training system for major natural disasters. Hence, this paper uncovers the visualization techniques commonly used in simulation training systems, and compares, analyses and summarizes the architecture and functions of the existing simulation training systems for different emergency phases of common natural disasters. In addition, the limitations of the existing simulation training system in practical applications and future development directions are discussed to provide reference for relevant researchers to better understand the modern simulation training system.