DEC1 is involved in circadian rhythm disruption-exacerbated pulmonary fibrosis.

BACKGROUND: The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS: In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-ß1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS: Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

PM2.5 exposure-induced senescence-associated secretory phenotype in airway smooth muscle cells contributes to airway remodeling.

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling.

(m) RVD-hemopressin (α) Ameliorated Oxidative Stress, Apoptosis and Damage to the BDNF/TrkB/Akt Pathway Induced by Scopolamine in HT22 Cells.

Dysfunction in the cholinergic system and oxidative stress are closely related and play roles in Alzheimer's disease (AD). Scopolamine (Scop), which is commonly used to induce cholinergic system damage in cells and animals, also evokes oxidative stress. Our previous study indicated that the peptide (m) RVD-hemopressin (RVD) reversed the memory-impairing effect of Scop in mice by activating cannabinoid receptor 1 (CBR1), but the mechanism was unclear. In this study, we found that RVD inhibited the oxidative stress, apoptosis, decreased cell viability and downregulation of synapse-associated proteins induced by Scop in HT22 cells. The effect was associated with the BDNF/TrkB/Akt pathway, and the effects of RVD outlined above could be blocked by an antagonist of CBR1. These results suggest that RVD may be a potential drug candidate for disorders associated with damage to the cholinergic system and oxidative stress, such as AD.

Lutein inhibits tumor progression through the ATR/Chk1/p53 signaling pathway in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment.

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Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is highly contagious and can cause death in severe cases. As reported by the World Health Organization (WHO), as of 6:36 pm Central European Summer Time (CEST), 12 August 2022, there had been 585 950 285 confirmed cases of COVID-19, including 6 425 422 deaths (WHO, 2022).

BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma.

BACKGROUND: Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. RESULTS: In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. CONCLUSIONS: Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Video Abstract.

Application and prospect of organic acid pretreatment in lignocellulosic biomass separation: A review.

As a clean and efficient method of lignocellulosic biomass separation, organic acid pretreatment has attracted extensive research. Hemicellulose or lignin is selectively isolated and the cellulose structure is preserved. Effective fractionation of lignocellulosic biomass is achieved. The separation characteristics of hemicellulose or lignin by different organic acids were summarized. The organic acids of hemicellulose were separated into hydrogen ionized, autocatalytic and α-hydroxy acids according to the separation mechanism. The separation of lignin depends on the dissolution mechanism and spatial effect of organic acids. In addition, the challenges and prospects of organic acid pretreatment were analyzed. The separation of hemicellulose and enzymatic hydrolysis of cellulose were significantly affected by the polycondensation of lignin, which is effectively inhibited by the addition of green additives such as ketones or alcohols. Lignin separation was improved by developing a deep eutectic solvent treatment based on organic acid pretreatment. This work provides support for efficient cleaning of carbohydrate polymers and lignin to promote global carbon neutrality.

Electromagnetic absorption enhancing mechanisms by modified biochar derived from Enteromorpha prolifera: a combined experimental and simulation study.

Although the rapid advances of wireless technologies and electronic devices largely improve the quality of life, electromagnetic (EM) pollution increases the risk of exposure to EM radiation. Developing high-efficiency absorbers with a rational structure and wideband characteristics is of great significance to eliminate radiation pollution. Herein, Enteromorpha prolifera derived biochar which would provide a suitable surface and multiple polarizations has been prepared as the supporter to anchor nanoparticles. In addition, theoretical simulation results further confirm that radar wave scattering could be largely inhibited after coating with absorbing materials. As a result, the hybrid absorbers achieve remarkable EM absorption properties attributed to the synergistic magnetic-dielectric loss. Elaborate compositional and structural characterization studies indicate that the absorber has a large specific area and numerous polarization centers, which would make full use of waste biomass as light weight and broadband high-performance EM absorption materials.

A New Predictive Model for the Prognosis of MDA5+ DM-ILD.

Purpose: The purpose of this study is to analyze clinical information and combine significant parameters to generate a predictive model and achieve a better prognosis prediction of dermatomyositis-associated interstitial lung disease with positive melanoma differentiation-associated gene 5 antibody (MDA5+ DM-ILD) and stratify patients according to prognostic risk factors appropriately. Methods: We retrospectively reviewed 63 patients MDA5+ DM-ILD who were treated in our hospital from January 2018 to January 2021. Our study incorporated most clinical characteristics in clinical practice to explore the associations and predictive functions of clinical characteristics and prognosis. Student's t-test, Mann-Whitney U-test, chi-squared test, Pearson correlation analysis, Cox regression analysis, R, receiver operating characteristic curves (ROC curves), and Kaplan-Meier survival curves were performed to identify independent predictors for the prognosis of MDA5+DM-ILD. Results: In all the 63 patients with MDA5+DM-ILD, 44 improved but 19 did not. Poor prognosis was found more frequently in patients who were older, clinically amyopathic variant of dermatomyositis (CADM), and/or with short duration, short interval of DM and ILD, long length of stay, fever, dyspnea, non-arthralgia, pulmonary infection, pleural effusion (PE), high total computed tomography scores (TCTs), ground-glass opacity (GGO), consolidation score, reticular score and fibrosis score, decreased forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), albumin, A/G, glomerular filtration rate (GFR) and tumor necrosis factor α (TNFα), high titer of anti-MDA5, proteinuria, high levels of monocyte, lactate dehydrogenase (LDH), ferritin (FER), neuron specific enolase (NSE) and glucocorticoid, antibiotic, antiviral, and non-invasive positive pressure ventilation (NPPV). The multivariate Cox regression analysis demonstrated that duration, fever, PE, TCTs and aspartate transaminase (AST) were independent predictors of poor prognosis in patients with MDA5+DM-ILD. The nomogram model quantified the risk of 400-day death as: duration ≤ 4 months (5 points), fever (88 points), PE (21 points), TCTs ≥10 points (22 points), and AST ≥200 U/L (100 points) with high predictive accuracy and convenience. The ROC curves possessed good discriminative ability for combination of fever, PE, TCTs, and AST, as reflected by the area under curve (AUC) being.954, 95% CI 0.902-1.000, and sensitivity and specificity being 84.2 and 94.6%, respectively. Conclusion: We demonstrated that duration, fever, PE, TCTs, and AST could be integrated together to be independent predictors of poor prognosis in MDA5+ DM-ILD with highly predictive accuracy.

Pleural mesothelial cell migration into lung parenchyma by calpain contributes to idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia. It is unknown why fibrosis in IPF distributes in the peripheral or named sub-pleural area. Migration of pleural mesothelial cells (PMC) should contribute to sub-pleural fibrosis. Calpain is known to be involved in cell migration, but the role of calpain in PMC migration has not been investigated. In this study, we found that PMCs migrated into lung parenchyma in patients with IPF. Then using Wt1tm1(EGFP/Cre)Wtp /J knock-in mice, we observed PMC migration into lung parenchyma in bleomycin-induced pleural fibrosis models, and calpain inhibitor attenuated pulmonary fibrosis with prevention of PMC migration. In vitro studies revealed that bleomycin and transforming growth factor-ß1 increased calpain activity in PMCs, and activated calpain-mediated focal adhesion (FA) turnover as well as cell migration, cell proliferation, and collagen-I synthesis. Furthermore, we determined that calpain cleaved FA kinase in both C-terminal and N-terminal regions, which mediated FA turnover. Lastly, the data revealed that activated calpain was also involved in phosphorylation of cofilin-1, and p-cofilin-1 induced PMC migration. Taken together, this study provides evidence that calpain mediates PMC migration into lung parenchyma to promote sub-pleural fibrosis in IPF.

Long-Term Effects of COVID-19 on Health Care Workers 1-Year Post-Discharge in Wuhan.

INTRODUCTION: To assess the long-term consequences of coronavirus disease (COVID-19) among health care workers (HCWs) in China (hereafter surviving HCWs). METHODS: A total of 303 surviving HCWs were included. Lung (pulmonary function test, 6-min walk test [6MWT], chest CT), physical (St. George's Respiratory Questionnaire [SGRQ], Modified Medical Research Council dyspnea scale [mMRC], and Borg scale), and psychiatric functions (Essen Trauma Inventory) were evaluated during the 1-year follow-up. RESULTS: Surviving HCWs had an abnormal diffusion capacity 1 year post-discharge. Participants with a reduced carbon monoxide diffusing capacity (DLCO) comprised 43.48%. The proportion of HCWs with a median 6MWT distance below the lower limit of the normal was 19.4%. An abnormal CT pattern was observed in 37.5% of the HCWs. The SGRQ, mMRC, and Borg scores of surviving HCWs, especially those with critical/severe disease, were significantly higher than those in the normal population. Probable post-traumatic stress disorder (PTSD) was reported in 21.9% of the surviving HCWs. Diffusion capacity impairment was associated with women. Critical/severe illness and nurses were associated with impaired physical function. CONCLUSIONS: Most surviving HCWs, especially female HCWs, still had an abnormal diffusion capacity at 1 year. The physical and psychiatric functions of surviving HCWs were significantly worse than those of the healthy population. Long-term follow-up of pulmonary, physical, and psychiatric functions for surviving HCWs is required.

Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment and Consulting Doctor Later: A Retrospective Cohort Study.

OBJECTIVE: To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding. METHODS: Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis. RESULTS: Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8-30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P<0.001), CRP (P=0.005) and more lobes lung lesion (P=0.014) on admission, as well as older age (P=0.017) and more patients with hypertension (P=0.044) than in those the virus shedding less than 23 days. Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol >8 days after symptom onset [OR: 2.447, 95% CI (1.351-4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035-3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474-7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191-0.690)]. CONCLUSION: Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study.

BACKGROUND: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China. METHODS: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ2, and Fisher's exact test were used to assess the variance between two or more groups where appropriate. RESULTS: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3+ T cells and CD4+ T cells. CONCLUSION: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.

Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever.

BACKGROUND: Most COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear. METHODS: We compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation. RESULTS: Among 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus, were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis. CONCLUSION: Gut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.

Splicing factor SRSF6 mediates pleural fibrosis.

Pleural fibrosis is defined as an excessive deposition of extracellular matrix that results in destruction of the normal pleural tissue architecture and compromised function. Tuberculous pleurisy, asbestos injury, and rheumatoid pleurisy are main causes of pleural fibrosis. Pleural mesothelial cells (PMCs) play a key role in pleural fibrosis. However, detailed mechanisms are poorly understood. Serine/arginine-rich protein SRSF6 belongs to a family of highly conserved RNA-binding splicing-factor proteins. Based on its known functions, SRSF6 should be expected to play a role in fibrotic diseases. However, the role of SRSF6 in pleural fibrosis remains unknown. In this study, SRSF6 protein was found to be increased in cells of tuberculous pleural effusions (TBPE) from patients, and decellularized TBPE, bleomycin, and TGF-ß1 were confirmed to increase SRSF6 levels in PMCs. In vitro, SRSF6 mediated PMC proliferation and synthesis of the main fibrotic protein COL1A2. In vivo, SRSF6 inhibition prevented mouse experimental pleural fibrosis. Finally, activated SMAD2/3, increased SOX4, and depressed miRNA-506-3p were associated with SRSF6 upregulation in PMCs. These observations support a model in which SRSF6 induces pleural fibrosis through a cluster pathway, including SRSF6/WNT5A and SRSF6/SMAD1/5/9 signaling. In conclusion, we propose inhibition of the splicing factor SRSF6 as a strategy for treatment of pleural fibrosis.

VEGF/Src signaling mediated pleural barrier damage and increased permeability contributes to subpleural pulmonary fibrosis.

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson's and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.

Corticosteroids Treatment of Patients with Coronavirus Disease 2019: A Propensity Score Matching Study.

The role of corticosteroids in the treatment of Coronavirus disease 2019 (COVID-19) is controversial. In the present study, we evaluated the effects of adjuvant corticosteroids treatment on the outcome of patients with COVID-19 (n=966), using Propensity Score Matching to adjust for potential differences between the corticosteroids group (n=289) and the non-corticosteroids group (n=677). Analysis of data without adjusting differences in baseline characteristics indicated that the proportion of mechanical ventilation and the mortality was higher in the corticosteroids treatment group in total or severe/critical patients. The duration of viral shedding was longer in the non-corticosteroids treatment group in total or general/mild patients. After adjusting the difference between the corticosteroids and non-corticosteroids treatment group, the analysis revealed that the use of corticosteroids had no effect on the duration of viral shedding, in-hospital mortality or 28-day mortality.

Co-infection of SARS-COV-2 and Influenza A Virus: A Case Series and Fast Review.

Coronavirus disease 2019 (COVID-19) occurs in the influenza season and has become a global pandemic. The present study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection with influenza A virus (IAV) in an attempt to provide clues for the antiviral interventions of co-infected patients. We described two patients who were co-infected with SARS-CoV-2 and IAV treated at Wuhan Union Hospital, China. In addition, we performed a review in PubMed, Web of Science and CNKI (from January 1 up to November 1, 2020) with combinations of the following key words: "COVID-19, SARS-COV-2, influenza A and co-infection". A total of 28 co-infected patients were enrolled in the analysis. Of the 28 patients, the median age was 54.5 years (IQR, 34.25-67.5) and 14 cases (50.0%) were classified as severe types. The most common symptoms were fever (85.71%), cough (82.14%) and dyspnea (60.71%). Sixteen patients had lymphocytopenia on admission and 23 patients exhibited abnormal radiological changes. The median time from symptom onset to hospital admission was 4 days (IQR, 3-6), and the median time of hospital stay was 14 days (IQR, 8.5-16.75). In conclusion, patients with SARS-COV-2 and IAV co-infection were similar to those infected with SARS-COV-2 alone in symptoms and radiological images. SARS-COV-2 co-infection with IAV could lead to more severe clinical condition but did not experience longer hospital stay compared with patients infected with SARS-COV-2 alone.

Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial.

BACKGROUND: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. OBJECTIVE: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. METHODS: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization. RESULTS: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05). CONCLUSIONS: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04273321.

Novel risk scoring system for predicting acute respiratory distress syndrome among hospitalized patients with coronavirus disease 2019 in Wuhan, China.

BACKGROUND: The mortality rate from acute respiratory distress syndrome (ARDS) is high among hospitalized patients with coronavirus disease 2019 (COVID-19). Hence, risk evaluation tools are required to immediately identify high-risk patients upon admission for early intervention. METHODS: A cohort of 220 consecutive patients with COVID-19 were included in this study. To analyze the risk factors of ARDS, data obtained from approximately 70% of the participants were randomly selected and used as training dataset to establish a logistic regression model. Meanwhile, data obtained from the remaining 30% of the participants were used as test dataset to validate the effect of the model. RESULTS: Lactate dehydrogenase, blood urea nitrogen, D-dimer, procalcitonin, and ferritin levels were included in the risk score system and were assigned a score of 25, 15, 34, 20, and 24, respectively. The cutoff value for the total score was > 35, with a sensitivity of 100.00% and specificity of 81.20%. The area under the receiver operating characteristic curve and the Hosmer-Lemeshow test were 0.967 (95% confidence interval [CI]: 0.925-0.989) and 0.437(P Value = 0.437). The model had excellent discrimination and calibration during internal validation. CONCLUSIONS: The novel risk score may be a valuable risk evaluation tool for screening patients with COVID-19 who are at high risk of ARDS.