This study aimed to develop a predictive model for secondary infections in patients with severe or critical COVID-19 by analyzing clinical characteristics and laboratory indicators.

A total of 307 patients with severe or critical COVID-19 admitted to Peking University Third Hospital from December 2022 to February 2023 were retrospectively analyzed, including 156 patients with secondary infection and 151 patients without secondary infection. The Boruta algorithm identified significant variables, and eight machine learning models were evaluated based on area under the curve (AUC) performance. The optimal model selected was further assessed, with model interpretability provided using SHapley Additive exPlanations (SHAP).

Nine predictive factors were identified: Mechanical Ventilation, Procalcitonin (PCT), Interleukin-8 (IL-8), Interleukin-6 (IL-6), Blood Urea Nitrogen, Glucose, Creatine Kinase, Lactate Dehydrogenase, and Mean Platelet Volume (MPV). The random forest model demonstrated the best performance, with further evaluation showing an average AUC of 0.981 (CI 0.965-0.998) on the training set and 0.836 (CI 0.761-0.912) on the test set. SHAP analysis identified MPV, PCT, and IL-8 as the strongest predictors of secondary infections.

We developed an effective predictive model for secondary infection risk in severe COVID-19 patients using readily available clinical parameters, enabling early clinical intervention. This machine learning approach demonstrates potential for improving patient management.

This study does not involve clinical trial interventions. Therefore, clinical trial registration was not applicable.

Chromatin remodeling factors are involved in the inflammatory responses, contributing to tissue damage and multi-organ dysfunction in COVID-19 patients. However, the underlying mechanisms remain unclear. In this study, high-dimensional analyses of single-cell RNA sequencing and single-cell ATAC sequencing data revealed increased chromatin accessibility at the promoters or enhancers of the pro-inflammatory cytokine tissue inhibitor of metalloproteinase-1 (TIMP1), as well as altered gene transcription profiles in monocytes from COVID-19 patients. Motif enrichment and positive regulators analyses identified SMARCC1, the core subunit of the chromatin remodeling complex, and the transcription factor JUND as positive regulators to co-modulate TIMP1 expression. In-vitro experiments, co-immunoprecipitation and chromatin immunoprecipitation (ChIP)-qPCR, and others, demonstrated the collaboration of SMARCC1 and JUND. Increased 7α,25-dihydroxycholesterol (7α,25-OHC) enhanced SMARCC1-JUND interactions to co-regulate TIMP1 expression. Further investigation indicated that 7α,25-OHC promoted the expression of SMARCC1 and its co-localization with H3K27ac, which involved in the expression of TIMP1 and inflammatory responses. Our study highlights the critical roles of SMARCC1 and JUND in COVID-19 inflammation, and offers the potential targets for the prevention and treatment of COVID-19.

Severe respiratory viral infections can lead to viral sepsis (VS), a life-threatening condition characterized by lung and extrapulmonary organ dysfunction. However, the pathology of VS is not clear. Specifically, it is unknown how the cytokine storm and direct virus infection contribute to the damage of extrapulmonary organs.

In this study, we established survival and lethal mouse models of VS by intranasally administering different doses of PR8/H1N1 influenza virus in C57BL/6J male mice, as well as model of bacterial sepsis (BS) caused by Streptococcus pneumoniae as references. Viraemia and extrapulmonary dissemination and infection of the virus were examined. Single-cell sequencing of the lungs and livers was performed at different days post-infection (dpi) in three groups.

While bacteria can spread and colonize extensively in extrapulmonary organs, causing multiple organ injuries, IAVs mainly replicate and cause damage in pulmonary cells. Live virus can be isolated in the blood and extrapulmonary organs. Disseminating via the bloodstream, IAVs transiently infect the liver and spleen, causing liver dysfunction and spleen atrophy, without affecting kidney function, despite systematically elevated cytokine levels. Compared to BS, a more significant decrease in the proportion of alveolar macrophages, epithelial cells, endothelial cells, and fibroblasts in the lungs, as well as endothelial cells and Kupffer cells in the liver, was observed in VS. This was accompanied by a longer activated PANoptosis pathway and downregulated genes responsible for barrier function and antigen presentation in the epithelial and endothelial cells.

Our study suggests that H1N1 influenza virus disseminates through the bloodstream and infects extrapulmonary organs to varying extents, which may lead to differential cell death, organ dysfunction, and trigger VS.

This research was supported by the National Natural Science Foundation of China (82241056, 82170015, 82030002, 82470007, 824B2001), the National Key R&D Program of China (2023YFC2306300), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-048), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208), New Cornerstone Science Foundation, National High Level Hospital Clinical Research Funding (2024-NHLHCRF-LX-01-0101, 2024-NHLHCRF-LX-01-0102), Beijing Research Ward Excellence Program (BRWEP2024W114060103), Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0506200, 2023ZD0506203) and Special Research Fund for Central Universities, Peking Union Medical College (3332024193).

Molecular hydrogen is gaining increasing attention as an antioxidant, anti-inflammatory, and antiapoptotic agent. Once considered an inert gas, it reveals current therapeutic potential among others in inflammatory diseases, cancer, and sports medicine, among others. The present review aims to provide a consistent summary of the findings of the last twenty years on the use of molecular hydrogen in major respiratory diseases, including allergies, asthma, COPD, pulmonary fibrosis, lung injury of various origins, as well as cancer and infections of the respiratory tract. In addition, the basic mechanisms through which molecular hydrogen exercises its biological activity on the respiratory system are described.

With the concurrent circulations of SARS-CoV-2 omicron and influenza A viruses in the community, there is evidence showing co-infection with both viruses. However, disease severity may vary due to the complex immunity landscape of the patients and the neutralizing antibody waning status. The intrinsic dynamic relationship and pathological significance for such co-infections remain largely unknown. The replication kinetics and innate immune responses from the co-infections of SARS-CoV-2 (Omicron BA.1 and D614G variant) and influenza A viruses (pandemic H1N1, seasonal H3N2 and highly pathogenic avian H5N1) were characterized in human respiratory tissue explants, human airway, and alveolar epithelial cells. SARS-CoV-2 reduced the replication of influenza A viruses, but not vice versa, during co-infections in human bronchial tissues and airway epithelial cells. In lung tissues, the co-infections showed minimal effects on each other, but the viral replications of the two viruses were mutually reduced except for H1N1pdm in the alveolar epithelial cells irrespective of the enhancement of the ACE2 receptor. Notably, the co-infections showed a significant upregulation of the innate immune responses of SARS-CoV-2 in comparison to single infections in both respiratory epithelial cells, suggesting that co-infections of influenza A viruses potentially lead to more severe damage to the host than SARS-CoV-2 single infections.

Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states.

This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff.

This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection.

NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; Epub ahead of print.

The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents.

We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells.

Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

Monocytes represent a vital cellular subpopulation in the peripheral blood, crucial in the progression of sepsis. Nonetheless, the prognostic role and precise function of monocytes in sepsis are still inadequately understood.

Single-cell transcriptomic sequencing and bioinformatics analysis were performed on peripheral blood samples from septic patients to identify key molecules in cell subsets. Subsequently, the expression pattern of this molecule was validated through diverse biological experiments, encompassing quantitative RT-PCR, western blotting, and immunofluorescence. Finally, the functionality of this molecule was evaluated using its specific agonist.

A total of 22 monocytes-related biomarkers were identified from single-cell and bulk RNA-seq analyses. Initially, LASSO analysis was performed to derive a prognostic signature composed of 4 key genes, including CD14, CTSS, CXCL8 and THBS1. Subsequently, mendelian randomization and survival analysis demonstrated that only CTSS showed crucially protective role in sepsis development and prognosis. Next, CTSS was confirmed to be lower expressed in peripheral monocytes of septic patients. Inflammatory markers (p < 0.05) and migration ability of LPS-activated monocytes were significantly reduced after CTSS agonist. In addition, CTSS agonist decreased the pulmonary tissue monocyte/macrophages infiltration in septic mice.

Monocyte marker CTSS represent a promising target for the diagnosis and prognosis evaluation of sepsis and plays a critical role in monocytes activation, tissue inflammatory response and macrophages infiltration. Thus, CTSS agonist probably serves as new drug for clinical protection against sepsis.

Sepsis, a critical condition caused by a dysregulated host response to infection, has high morbidity and mortality rates. Timely diagnosis and treatment are vital for improving patient outcomes. This study explores the potential role of CXCL5 in the diagnosis, severity assessment, and prognosis of sepsis.

We included 147 sepsis patients, 50 patients with systemic inflammatory response syndrome (SIRS) and 120 healthy controls. Serum CXCL5 levels, inflammation scores (APACHE II, SOFA), and other laboratory indicators were recorded. Univariate and multivariate logistic regression analyses were conducted to assess the relationship between CXCL5 and sepsis diagnosis, severity, and prognosis. A prognostic nomogram was constructed and evaluated using receiver operator characteristic curves, calibration curves, and clinical decision curves.

Serum CXCL5 levels in sepsis patients were significantly higher than those in patients with SIRS and healthy controls. CXCL5 was identified as a risk factor for sepsis diagnosis. CXCL5 levels were significantly elevated in patients with septic shock (P = 0.04) and in deceased patients compared to survivors (P < 0.001). The prognostic model, incorporating CXCL5, lactate, APACHE II scores, C-reactive protein levels, and respiratory rate, demonstrated high predictive accuracy with an area under the curve of 0.873. Calibration and decision curve analyses demonstrated the model's good predictive performance and potential clinical value.

Serum CXCL5 concentration is a promising biomarker for enhancing the diagnostic accuracy and prognostic evaluation of sepsis. The constructed multivariate prediction model offers new insights into sepsis prognosis, but its direct application in clinical practice requires further validation.

COVID-19 exhibits complex pathophysiological manifestations, characterized by significant clinical and biological heterogeneity. Identifying phenotypes may enhance our understanding of the disease's diverse trajectories, benefiting clinical practice and trials.

This study included adult patients with COVID-19 from Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, between December 15, 2022, and February 15, 2023. The k-prototypes clustering method was employed using 50 clinical variables to identify phenotypes. Machine learning algorithms were then applied to select key classifier variables for phenotype recognition.

A total of 1376 patients met the inclusion criteria. K-prototypes clustering revealed two distinct subphenotypes: Hypo-inflammatory subphenotype (824 [59.9%]) and Hyper-inflammatory subphenotype (552 [40.1%]). Patients in Hypo-inflammatory subphenotype were younger, predominantly female, with low mortality and shorter hospital stays. In contrast, Hyper-inflammatory subphenotype patients were older, predominantly male, exhibiting a hyperinflammatory state with higher mortality and rates of organ dysfunction. The AdaBoost model performed best for subphenotype prediction (Accuracy: 0.975, Precision: 0.968, Recall: 0.976, F1: 0.972, AUROC: 0.975). "CRP", "IL-2R", "D-dimer", "ST2", "BUN", "NT-proBNP", "neutrophil percentage", and "lymphocyte count" were identified as the top-ranked variables in the AdaBoost model.

This analysis identified two phenotypes based on COVID-19 symptoms and comorbidities. These phenotypes can be accurately recognized using machine learning models, with the AdaBoost model being optimal for predicting in-hospital mortality. The variables "CRP", "IL-2R", "D-dimer", "ST2", "BUN", "NT-proBNP", "neutrophil percentage", and "lymphocyte count" play a significant role in the prediction of subphenotypes. Use the identified subphenotypes for risk stratification in clinical practice. Hyper-inflammatory subphenotypes can be closely monitored, and preventive measures such as early admission to the intensive care unit or prophylactic anticoagulation can be taken.

The clinical manifestations of the cytokine storm (CS) associated with COVID-19 resemble the acute phase of sepsis. Metabolomics may contribute to understanding the specific pathobiology of these two syndromes. The aim of this study was to compare serum metabolomic profiles in CS associated with COVID-19 vs. septic surgery patients. In a retrospective cross-sectional study, serum samples from patients with CS associated with COVID-19, with and without comorbidity, as well as serum samples from patients with surgical sepsis were investigated. Targeted metabolomic analysis was performed on all samples using LC-MS/MS. Analysis revealed that similar alterations in the serum metabolome of patients with COVID-19 and surgical septic patients were associated with amino acid metabolism, nitrogen metabolism, inflammatory status, methionine cycle and glycolysis. The most significant difference was found for serum levels of metabolites of kynurenine synthesis, tricarboxylic acid cycle, gamma-aminobutyric acid and niacinamide. The metabolic pathway of cysteine and methionine metabolism was significantly disturbed in COVID-19 and surgical septic patients. For the first time, the similarities and differences between the serum metabolomic profiles of patients with CS associated with COVID-19 and patients with surgical sepsis were investigated for patients from the Northwest of the Russian Federation.

The intricacies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing acute lung injury (ALI) and modulating inflammatory factor dynamics in vivo remain poorly elucidated. The present study endeavors to explore the impact of the recombinant SARS-CoV-2 spike protein S1 subunit (S1SP) on ALI and inflammatory factor profiles in mice, aiming to uncover potential therapeutic targets and intervention strategies for the prevention and management of Coronavirus Disease 2019 (COVID-19).

To mimic COVID-19 infection, K18-hACE2 transgenic mice were intratracheally instilled with S1SP, while C57BL/6 mice were administered LPS to form a positive control group. This setup facilitated the examination of lung injury severity, inflammatory factor levels, and alterations in signaling pathways in mice mimicking COVID-19 infection. Histopathological assessment through HE staining, along with analysis of lung wet/dry ratio and ultrasound imaging, revealed severe lung injury.

After molding, K18-hACE2 mice exhibited a pronounced reduction in body weight and showed more significant lung injury (P < 0.05). Notably, there was a significant elevation in vascular permeability, total protein, and total white blood cells in bronchoalveolar lavage fluid (BALF) (P < 0.05), indicative of tissue damage. Additionally, the tight junction of lung tissue was compromised (P < 0.05), accompanied by intense oxidative stress marked by decreased SOD activity and elevated MDA content (P < 0.05). Cytokine levels, including IL-6, IL-1β, TNF-α, and MIG, were significantly upregulated in both BALF and serum of S1SP + K18 mice (P < 0.05). Furthermore, S1SP prominently augmented the expression of p-p65/P65 and attenuated IκBα expression in the NF-κB signaling pathway of humanized mice (P < 0.05), corroborating a heightened inflammatory response at the tissue level (P < 0.05).

The administration of S1SP to K18-hACE2 mice resulted in severe lung injury, enhanced vascular permeability, and compromised epithelial barrier function in vivo. This was accompanied by disruption of lung tight junctions, the manifestation of severe oxidative stress and a cytokine storm, as well as the activation of the NF-κB signaling pathway, highlighting key pathological processes underlying COVID-19-induced lung injury.

Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs. To test this hypothesis, we developed AdV.C3-Tat/HIV-Box A, an inflammation-inducible cassette that remains innocuous in the absence of inflammation but releases HMGB1 Box A, an antagonist of high mobility group box 1 (HMGB1), in response to inflammatory stimuli such as lipopolysaccharide (LPS) or influenza virus infection. We report here that this novel inflammation-inducible HMGB1 Box A construct in a non-replicative adenovirus (AdV) vector mitigates lung and systemic inflammation therapeutically in response to influenza infection. We anticipate that this strategy will apply to the treatment of multiple diseases in which HMGB1-mediated signaling is a central driver of inflammation.IMPORTANCEMany inflammatory diseases are mediated by the action of a host-derived protein, HMGB1, on Toll-like receptor 4 (TLR4) to elicit an inflammatory response. We have engineered a non-replicative AdV vector that produces HMGB1 Box A, an antagonist of HMGB1-induced inflammation, under the control of an endogenous complement component C3 (C3) promoter sequence, that is inducible by LPS and influenza in vitro and ex vivo in macrophages (Mϕ) and protects mice and cotton rats therapeutically against infection with mouse-adapted and human non-adapted influenza strains, respectively, in vivo. We anticipate that this novel strategy will apply to the treatment of multiple infectious and non-infectious diseases in which HMGB1-mediated TLR4 signaling is a central driver of inflammation.

To evaluate the all-cause mortality rate and renal outcomes in patients with diabetes and chronic kidney disease (CKD) following hospital discharge for COVID-19.

This single-center prospective observational study included 187 discharged COVID-19 patients with diabetes and CKD, admitted between December 2022 and January 2023 at West China Hospital, Sichuan University. Cox regression analysis was used to assess mortality risk, and logistic regression was applied to identify risk factors for rapid CKD progression after discharge.

During the one-year follow-up, the all-cause mortality rate was 26.7%, with a COVID-19-related acute kidney injury (AKI) incidence of 35.3%, and 35.8% of patients experienced rapid CKD progression after discharge. Cox proportional hazards regression indicated that sepsis and mechanical ventilation were major risk factors for post-discharge all-cause mortality. Logistic regression identified baseline eGFR < 60 mL/min/1.73 m² as an independent risk factor for rapid CKD progression.

During the one-year follow-up period, we observed that patients with diabetes and CKD exhibited higher all-cause mortality and experienced rapid deterioration of kidney function after acute infection with COVID-19. This underscores the importance of ongoing longitudinal follow-up to more accurately track the long-term health effects of COVID-19 on patients with diabetes and CKD.

The risk of thrombosis increases after SARS-CoV-2 infection. This study aimed to assess associations between pre-infection anticoagulant exposure and SARS-CoV-2 infection-related outcomes in a population-based cohort.

Members of the "Meuhedet" health maintenance organization aged >45 years who tested positive for SARS-CoV-2 infection (03/2020-04/2022) were followed. Pre-infection anticoagulant exposure (PAE) was defined as any anticoagulant therapy prescribed ≥1 month prior to SARS-CoV-2 testing. Univariate analyses, multivariable models adjusting for confounders, propensity-score matching, and an age-stratified analysis were performed to assess associations between PAE and hospitalization, intensive care unit (ICU) admission, 30-day and one-year mortality.

Of the 127,801 patients included, 2951(2.3 %) had PAE. Comorbidities including ischemic heart disease, diabetes mellitus, hypertension, heart failure, and atrial fibrillation were more common among anticoagulant-exposed than unexposed individuals (p < 0.001). Patients with PAE experienced higher hospitalization (22.7 % vs 5.6 %), ICU admissions (1.9 % vs 0.5 %), 30-day and 1-year mortality rates (4.8 % vs. 0.6, and 8.8 % vs. 1.1 %, respectively), than unexposed individuals, but similar lengths-of-stay. In the multivariable analysis, PAE was independently associated only with hospitalizations (adjusted odds ratio (aOR) = 1.29 [95 % confidence interval (CI): 1.13-1.47]), whereas in the propensity-matched analysis, none of the outcomes differed significantly between the groups. However, in the stratum aged >75 years, 30-day and one-year mortality were significantly reduced in those with PAE (aOR = 0.68 [CI:0.48-0.97], and aOR = 0.73 [CI:0.55-0.97], respectively).

SARS-CoV-2-infected individuals with prior exposure to anticoagulants have more comorbidities and experienced a higher incidence of hospitalization but not mortality compared to unexposed patients. Paradoxically, mortality risks decreased in the oldest stratum of anticoagulant-exposed individuals. Further research is required to assess mechanisms for this apparent protective effect.

There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival.

We used biomaterial from 81 prospectively recruited patients from the multicentric CovidDataNet.NRW-study cohort (German clinical trial registry: DRKS00026184) with their collected medical history, vital signs, laboratory parameters, microbiological findings and patient outcome. ERK activity was measured by evaluating ERK phosphorylation using a Proximity Ligation Assay.

An increased ERK activity at 4 days after diagnosis of COVID-19-induced sepsis was associated with a more than threefold increased chance of survival in an adjusted Cox regression model. ERK activity was independent of other confounders such as Charlson Comorbidity Index or SOFA score (HR 0.28, 95% CI 0.10-0.84, p = 0.02).

High activity of the RAF/MEK/ERK network during the course of COVID-19 sepsis is a protective factor and may indicate recovery of the immune system. Further studies are needed to confirm these results.

The relationships between pectoralis muscle parameters and outcomes in patients with coronavirus disease 2019 (COVID-19) remain uncertain.

We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from 1 January 2019 to 1 May 2024 to identify non-overlapping studies evaluating pectoralis muscle-associated index on chest CT scan with clinical outcome in COVID-19 patients. Random-effects and fixed-effects meta-analyses were performed, and heterogeneity between studies was quantified using the I2 statistic. The risk of study bias was assessed using the Newcastle-Ottawa scale. Funnel plots for detecting small-study effects.

A total of 9 studies with 4109 COVID-19 patients were included. The meta-analysis findings revealed a correlation between pectoralis muscle parameters and COVID-19 prognosis. Specifically, patients with higher pectoralis muscle density (PMD) exhibited a lower mortality risk, with an odds ratio (OR) of 0.95 (95% CI: 0.92-0.99). The rate of intubation was lower in COVID-19 patients with a high pectoralis muscle index (PMI) (OR =  0.96, 95% CI: 0.92-1.00).

In summary, a low PMD is associated with a marginally elevated risk of mortality, whereas a decreased PMI represents a risk factor for intubation in COVID-19 patients. These findings suggest that pectoralis muscle parameters on chest CT may be a useful prognostic tool for COVID-19 patients.

Viremia has been detected in a significant proportion of patients with acute respiratory viral infection, yet its clinical value remains underappreciated.

This study synthesized available evidence to comprehensively assess the prevalence of viremia and its impact on clinical outcomes.

Data sources: Data were retrieved from Medline (via Ovid), Embase, and the WHO COVID-19 database.

This review included original clinical studies analysing the prevalence of viremia in patients with acute respiratory viral infection or its association with clinical outcomes, while excluding non-original research, insufficiently detailed studies, inconsistent pathogen observations, or those with inadequate sample sizes.

Patients with acute respiratory viral infection.

Newcastle-Ottawa scale and an adapted version were used.

Respiratory viral infection-related viremia.

Data synthesis utilized random-effects models to pool prevalence and hazard ratio (HR), OR, and adjusted HR/OR for clinical outcomes.

In the comprehensive analysis of viremia prevalence, data were pooled from 101 studies, which included a total of 16,388 non-overlapping patients. Viremia was present in 34% (95% CI, 28-41%) of patients with acute respiratory viral infection. A total of 45 studies provided information on the clinical outcomes of 2002 patients with viremia and 3907 patients without viremia. Viremia was associated with increased risks of mortality (OR, 6.83; 95% CI, 4.92-9.48; adjusted HR, 2.91; 95% CI, 1.87-4.53; adjusted OR, 3.68; 95% CI, 2.37-5.71), intensive care unit admission (OR, 4.74; 95% CI, 2.66-8.46; adjusted OR, 4.89; 95% CI, 1.61-14.91), mechanical ventilation (OR, 4.12; 95% CI, 2.25-7.52), and hepatic complications (OR, 3.10; 95% CI, 1.30-7.40).

Viremia is prevalent in patients with respiratory viral infection and is associated with elevated risks of adverse clinical outcomes.

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple organ dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, and intestinal systems. It is well-established that pathogen infections lead to immune dysregulation, which subsequently contributes to MODS in sepsis. However, recent evidence suggests that sepsis-related opportunistic pathogens can directly induce organ failure by promoting PCD in parenchymal cells of each affected organ. This study provides an overview of PCD in damaged organ and the induction of PCD in host parenchymal cells by opportunistic pathogens, proposing innovative strategies for preventing organ failure in sepsis.

Little was known about the characteristics of low respiratory tract (LRT) microbiota of refractory M. pneumoniae pneumonia (RMPP) in children before and after the COVID-19 pandemic.

Forty-two children diagnosed with RMPP in 2019 (Y2019 group) and 33 children diagnosed with RMPP in 2023 (Y2023 group), entered into the study. The characteristics of the clinical findings were examined, and the LRT microbiota was analyzed by metagenomic next generation sequencing.

The ratio of consolidate, atelectasis, lung necrosis, and erythema multiforme in Y2023 group was significantly higher than that in Y2019 (P<0.05). Mycoplasmoides pneumoniae was the top species of the LRT microbiota in both groups. The rate of macrolide resistance MP in Y2023 was significantly higher than that in Y2019 (P<0.05), and the mutant site was all 23S rRNA A2063G. There were no significant differences in α-diversity and β-diversity of LRT microbiota between Y2019 and Y2023 group. Trichoderma citrinoviride, Canine mastadenovirus A, Ralstonia pickettii, Lactococcus lactis, Pseudomonas aeruginosa were the biomarkers of LRT microbiota in children with RMPP of Y2023. The abundance of Mycoplasmoides pneumoniae positively correlated with the levels of D-dimer and LDH, negatively correlated with the counts of CD3+ T cells, CD8+ T cells, CD19+ B cells and CD16+CD56+ NK cells.

Our study showed that high abundance of MP was correlated with the severity of RMPP and decrease of immune cells. Trichoderma citrinoviride, Canine mastadenovirus A, Ralstonia pickettii, Lactococcus lactis, Pseudomonas aeruginosa were the biomarkers in microbiota of LRT in children with RMPP post COVID-19 era.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19). While SARS-CoV-2 primarily targets the lungs and airways, it can also infect other organs, including the central nervous system (CNS). The aim of this study was to investigate whether the choroid plexus could serve as a potential entry site for SARS-CoV-2 into the brain. Tissue samples from 24 deceased COVID-19-positive individuals were analyzed. Reverse transcription real-time PCR (RT-qPCR) was performed on selected brain regions, including the choroid plexus, to detect SARS-CoV-2 viral RNA. Additionally, immunofluorescence staining and confocal microscopy were used to detect and localize two characteristic proteins of SARS-CoV-2: the spike protein S1 and the nucleocapsid protein. RT-qPCR analysis confirmed the presence of SARS-CoV-2 viral RNA in the choroid plexus. Immunohistochemical staining revealed viral particles localized in the epithelial cells of the choroid plexus, with the spike protein S1 detected in the late endosomes. Our findings suggest that the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus serves as a route of entry for SARS-CoV-2 into the CNS. This study contributes to the understanding of the mechanisms underlying CNS involvement in COVID-19 and highlights the importance of further research to explore potential therapeutic strategies targeting this entry pathway.

Toll-like receptors (TLRs) of human are considered as the most critical immunological mediators of inflammatory pathogenesis of COVID-19. These immunoregulatory glycoproteins are located on the surface and/or intracellular compartment act as innate immune sensors. Upon binding with distinct SARS-CoV-2 ligand(s), TLRs signal activation of different transcription factors that induce expression of the proinflammatory mediators that collectively induce 'cytokine storm'. Similarly, TLR activation is also pivotal in conferring protection to infection and invasion as well as upregulating the tissue repair pathways. This dual role of the human TLRs in deciding the fate of SARS-CoV-2 has made these receptor proteins as the critical mediators of immunoprotective and immunopathogenic consequences associated with COVID-19. Herein, pathbreaking discoveries exploring the immunobiological importance of the TLRs in COVID-19 and developing TLR-directed therapeutic intervention have been reviewed by accessing the up-to-date literatures available in the public domain/databases. In accordance with our knowledge in association with the importance of TLRs' role against viruses and identification of viral particles, they have been recognized as suitable candidates with high potential as vaccine adjuvants. In this regard, the agonists of TLR4 and TLR9 have effective potential in vaccine technology while the others need further investigations. This comprehensive review suggests that basal level expression of TLRs can act as friends to keep our body safe from strangers but act as a foe via overexpression. Therefore, selective inhibition of the overexpressed TLRs appears to be a solution to counteract the cytokine storm while TLR-agonists as vaccine adjuvants could lessen the risk of infection in the naïve population.

Myasthenia gravis (MG) is characterized by fluctuating muscle weakness due to immune-mediated damage to acetylcholine receptors. Viral infections can exacerbate symptoms of muscle weakness, and the clinical status of patients with MG may influence the outcomes of such infections. Here, we identified factors of symptom exacerbation, severe SARS-CoV-2 infection, and pneumonia in patients with MG who are infected with SARS-CoV-2.

The clinical characteristics and outcomes of 341 MG patients infected with SARS-CoV-2 across multiple regions in China were determined.

The median age of the patients was 49 years (range: 35-60 years) and the median disease duration was 4 years (range: 2-8 years). Among the patients, 67 (49.0%) were male and 174 (51.0%) were female. Multivariate analysis indicated that thymectomy [OR, 1.654 (95% CI, 1.036-2.643); p = 0.035], severe SARS-CoV-2 infection [OR, 4.275 (95% CI, 2.206-8.286); p < 0.001], and pyridostigmine bromide [OR, 1.955 (95% CI, 1.192-3.206); p = 0.008] were associated with exacerbation of MG symptoms in patients infected with SARS-CoV-2. Age was significantly associated with severe SARS-CoV-2 infection [OR, 1.023 (95% CI, 1.001-1.046); p = 0.008], while patients with cardiac/vascular comorbidities exhibited an increased likelihood of severe SARS-CoV-2 infection [OR, 3.276 (95% CI, 1.027-10.449); p = 0.045]. Likewise, steroid treatment [OR, 6.140 (95% CI, 2.335-16.140); p < 0.001] was associated with a significantly increased likelihood of severe SARS-CoV-2 infection compared with symptomatic treatment. Additionally, gender [OR, 0.323 (95% CI, 0.120-0.868); p = 0.025] and SARS-CoV-2 severity [OR, 6.067 (95% CI, 1.953-18.850); p = 0.002] were associated with the occurrence of pneumonia.

We identified factors that were associated with the exacerbation of MG symptoms in patients infected with SARS-CoV-2, including thymectomy, severe SARS-CoV-2 infection, and the use of pyridostigmine bromide. Due to the retrospective nature of the study, these findings should be interpreted as associations rather than predictive factors. However, the results confirm the established relationships between severe SARS-CoV-2 infection and age, cardiovascular comorbidities, and the use of steroid treatment, suggesting that these factors should be considered when managing MG patients during SARS-CoV-2 infection.

Cardiovascular disease (CVD) is the leading cause of death in the United States, and sepsis significantly contributes to hospitalization and mortality. This study aims to assess the trends of sepsis-associated CVD mortality rates and variations in mortality based on demographics and regions in the US.

The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database was used to identify CVD and sepsis-related deaths from 1999 to 2022. Data on gender, race and ethnicity, age groups, region, and state classification were statistically analyzed to obtain crude and age-adjusted mortality rates (AAMR). The Joinpoint Regression Program was used to determine trends in mortality within the study period.

During the study period, there were a total of 1,842,641 deaths with both CVD and sepsis listed as a cause of death. Sepsis-associated CVD mortality decreased between 1999 and 2013, from AAMR of 65.7 in 1999 to 58.8 in 2013 (APC -1.06*%, 95% CI: -2.12% to -0.26%), then rose to 74.3 in 2022 (APC 3.23*%, 95% CI: 2.18%-5.40%). Throughout the study period, mortality rates were highest in men, NH Black adults, and elderly adults (65+ years old). The Northeast region, which had the highest mortality rate in the initial part of the study period, was the only region to see a decline in mortality, while the Northwest, Midwest, and Southern regions experienced significant increases in mortality rates.

Sepsis-associated CVD mortality has increased in the US over the past decade, and both this general trend and the demographic disparities have worsened since the onset of the COVID-19 pandemic.

Transmission of COVID-19 is now normalized. There is an association between it and increased incidence of febrile seizures in children. Exploring whether COVID-19 has a specific effect on the clinical and biochemical features of febrile seizures is critical for the development of clinical treatment and prevention strategies. This study is to compare the differences in clinical features, hematological features, and cerebrospinal fluid characteristics between COVID-19 and non-COVID-19 children with febrile seizures and to provide a new perspective for further exploring the impact of COVID-19 on the nervous system of children.

This was a retrospective case-control study. The cases included children with COVID-19 and non-COVID-19 febrile seizures admitted to Xiamen Children's Hospital from December 2022 to December 2023. The age, gender, length of hospital stay, peak body temperature, presence or absence of other viral infections, hematological characteristics, and cerebrospinal fluid characteristics were compared between children with COVID-19 febrile seizures and non-COVID-19 febrile seizures.

A total of 50 COVID-19 children with febrile seizures and 192 non-COVID-19 children with febrile seizures were enrolled in this study. Multivariate analysis showed that age (OR = 0.715, P = 0.031), blood urea nitrogen (OR = 0.454, P = 0.029), platelet count (OR = 0.987, P = 0.009) and magnesium ion concentration (OR = 0.109, P < 0.001) were negatively correlated with COVID-19 febrile seizures. Albumin (OR = 1.840, P < 0.001) was positively correlated. The concentration of potassium ion in cerebrospinal fluid (OR = 0.334, P = 0.012) was negatively correlated with COVID-19 febrile seizures, and the concentration of sodium ion (OR = 4.383, P = 0.022) was positively correlated with COVID-19 febrile seizures.

There were differences in age, blood urea nitrogen, platelet count, magnesium ion concentration, albumin, potassium ion concentration in cerebrospinal fluid, and sodium ion concentration in the cerebrospinal fluid between children with COVID-19 febrile seizures and non-COVID-19 febrile seizures. This study may provide valuable insights into the potential mechanisms of COVID-19 damage to the nervous system in children, and the long-term neurological prognosis of these children requires long-term follow-up.

HAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown a significant increase in serum levels of vascular permeability factor (VPF/VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to the pulmonary vascular endothelium. Further research is necessary to elucidate the underlying mechanism.

The human lung microvascular endothelial cell line-5a and human CD46 mice were used for in vitro and in vivo experiments, respectively. RNA-seq was employed for correlative omics analysis. Viral infection and copy status were examined using transmission electron microscopy to observe virus particles, immunofluorescence to detect the viral protein Hexon, and qPCR to assess HAdV-7 fiber gene copies. Various methods, including ELISAs for VEGF and other injury markers, the CCK8 assay for cell viability, and flow cytometry for endothelium numbers, were employed to evaluate endothelial damage. Acute lung injury severity was evaluated by scoring pathological inflammation and measuring pulmonary vascular permeability. Autophagy activation was assessed by observing autophagosomes and validating marker proteins.

GSEA analysis showed significant enrichment of gene sets related to endothelial functions (barrier, defense, and regeneration) and ALI in the HAdV-7-infected group. GO analysis indicated an enrichment of autophagy-related pathways linked to cell death. Subsequently, successful signs of HAdV-7 infection and replication were observed in the endothelium, including cytopathic effects, intracellular virions, and increased HAdV-7 fiber gene copies. Endothelial injury, including mitochondrial damage, decreased endothelium, and elevated levels of endothelial injury markers such as VEGF, sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, and IL1β were observed after HAdV-7 infection. Additionally, evidence of leaky lung blood vessels and ALI was observed, including progressive weight loss, elevated pulmonary vascular permeability, and severe lung consolidation. Furthermore, HAdV-7 infection induced autophagosome formation in the endothelium and triggered complete cell autophagy. Importantly, inhibiting autophagic flux reduced VEGF levels and other endothelial injury markers, decreased viral load, improved cell survival rate, alleviated pulmonary vessel leakage, and mitigated lung inflammation.

HAdV-7 successfully infects pulmonary vascular endothelium and replicates effectively, causing injury to the endothelium, high VEGF expression and viral load in the serum, as well as ALI/ARDS. Autophagy inhibitors can alleviate endothelial injury, inhibit viral replication, relieve leakage from the vasculature, and reduce lung inflammation.

Patients with cirrhosis are known to be prone to infections. Infections can trigger organ failures and decompensations in cirrhosis. Septic shock can increase mortality by fourfold and cause hemodynamic imbalances, adding to the already hyperdynamic circulation. Management of septic shock in cirrhosis can be tricky due to this complex interplay of altered hemodynamics, immune function, and coagulation.

In this review, we explore the pathophysiological basis, screening, monitoring and management of septic shock in cirrhosis. We also explore novel biomarkers, the growing challenge of multidrug-resistant pathogens and novel and adjunctive therapies. Finally, we propose an algorithm for the management of septic shock in cirrhosis. We conducted a comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library using the keywords and MeSH terms like 'septic shock,' 'cirrhosis,' 'liver disease,' 'sepsis' among others. The search was restricted to peer-reviewed articles in English.

The difficulties in managing septic shock in cirrhosis are discussed, emphasizing personalized approaches over protocol-driven care. Fluid and vasopressor management, antibiotic timing and selection, the role of adjunctive therapies, the importance of lactate clearance, gut failure, and the need for further research in this population are highlighted.

IL-1α/β and TNF are closely linked to the pathology of severe COVID-19 and sepsis. The soluble forms of their receptors, functioning as decoy receptors, exhibit inhibitory effects. However, little is known about their regulation in severe bacterial and viral infections, which we aimed to investigate in this study.

The circulating soluble receptors of TNF (sTNFR1 and sTNFR2) and IL-1α/β (sIL-1R1, sIL-1R2) were evaluated in the plasma of patients with COVID-19, severe bacterial infections, and sepsis and compared with healthy controls. Additionally, IL1R1, IL1R2, TNFRSF1A, and TNFRSF1B expression was evaluated at the single cell level in PBMCs derived from COVID-19 or sepsis patients.

Plasma concentrations of sIL-1R1, sTNFR1, and sTNFR2 were significantly higher in COVID-19 patients compared to healthy subjects. Notably, sIL-1R1 levels were particularly elevated in ICU COVID-19 patients, and transcriptome analysis indicated heightened IL1R1 expression in PBMCs from severe COVID-19 patients. In severe bacterial infections, only sTNFR1 and sTNFR2 exhibited increased levels compared to healthy controls. Sepsis patients had decreased sIL-1R1 plasma concentrations but elevated sIL-1R2, sTNFR1, and sTNFR2 levels compared to healthy individuals, reflecting the heightened expression due to the increased numbers of monocytes present in sepsis. Finally, elevated concentrations of sIL-1R2, sTNFR1, and sTNFR2 were moderately associated with reduced 28-day survival in sepsis patients.

Our study reveals distinct regulation of plasma concentrations of soluble IL-1 receptors in COVID-19 and sepsis. Moreover, soluble TNF receptors 1 and 2 consistently rise in all conditions and show a positive correlation with disease severity in sepsis.

BACKGROUND : The efficiency of medical services directly impacts the economic burden of healthcare, making it crucial to analyze the input-output efficiency of various types of medical institutions. However, while hospitals had been extensively analyzed for their efficiency, other types of medical institutions had received limited attention in this regard. METHODS : In this study, we employed data envelopment analysis (DEA) methods based on time series and internal benchmarks to autonomously assess the efficiency of 18 distinct categories of healthcare facilities in China over the past decade. The verification was conducted through the utilization of the critical incident technique (CIT). Additionally, we utilized the Delphi process (AHP) method to evaluate suppliers of medical consumables, implemented a multi-population genetic algorithm for managing these consumethod and analytic hierarchymables efficiently, and applied stakeholder theory to manage medical personnel efficiency.  RESULTS : Our findings indicated that medical institutions capable of providing clinical services exhibited higher levels of efficiency compared to those unable to do so. Multiple indicators suggested redundancy within these institutions. Notably, comprehensive benefit evaluation revealed that clinical laboratory had performed poorly over the past decade. We selected an inefficient medical institution for intervention in reagent management and the work efficiency of medical staff. After implementing the Delphi method and multi-population genetic algorithm for consumable replenishment, the reagent cost was reduced by 40%, 39% and 31% respectively in each of the three experimental groups, compared to the control group. By applying stakeholder theory and process reengineering methods, we were able to shorten quality control management time for medical staff in the experimental group by 41 min per day, reduce clinical service time by 25 min per day, and extend rest time by 70 min per day, while the quality indicators were all meeting the targets. CONCLUSION: By employing various mathematical models as described above, we were able to reduce costs associated with medical consumables and enhance medical personnel work efficiency without compromising quality objectives.

Septic cardiomyopathy (SCM), a complication initiated by sepsis, presents a significant clinical challenge, leading to increased mortality rates. However, the mechanisms of SCM have not been fully uncovered. Our study involved analyzing RNA sequencing (RNA-seq) data from rat heart tissue, along with utilizing molecular docking and molecular dynamics (MD) simulations, to discover key targets and potential pharmacological actions of the calcitonin gene-related peptide (CGRP) against SCM. A lipopolysaccharide-induced SCM model was established in rats (LPS 10 mg/kg, intraperitoneal (i.p.)). Thereafter, the myocardial tissues from the three groups of rats (Ctrl group, LPS group, and CGRP group) (n = 5) were extracted and underwent RNA-seq, followed by bioinformatics analyses. The qPCR-validated hub targets potentially interacting with CGRP were identified. Following this, homology modeling was utilized to obtain the 3D structure of hub targets, and molecular docking was conducted to evaluate the interaction between CGRP and hub targets. MD simulations (300 ns) were performed to confirm the findings further. Our findings demonstrated that CGRP significantly lowered mortality in SCM rats. 633 DEGs were affected by LPS, contrasted with the Ctrl group. 96 DEGs were affected by CGRP compared to the LPS group. In total, ten fully annotated CGRP-triggered hub genes were obtained. The molecular docking and MD simulations indicate that the relationship between CGRP and eight hub genes is extremely strong. This research offers a thorough examination of the possible objectives and fundamental molecular processes of CGRP in combating SCM, laying the groundwork for investigating the potential protective mechanisms of CGRP against SCM.

This study aimed to examine the potential prognostic significance of the D-dimer-albumin ratio (DAR) in critically ill patients with sepsis.

A retrospective cohort study was carried out at the Affiliated Hospital of Jiangsu University, involving 1123 patients diagnosed with sepsis from January 2015 to November 2023. The patients were categorized into four groups (Q1-Q4) based on their DAR levels. The primary outcomes measured were in-hospital mortality and ICU mortality. Survival analysis was conducted using Kaplan-Meier survival curves and the log-rank test. Additionally, Cox proportional hazards regression models were utilized to investigate the relationship between the DAR and all-cause mortality.

The study population had a median age of 75 years (interquartile range: 65-84), and the median DAR was 0.15 (interquartile range: 0.08-0.32). The rates of hospital mortality and ICU mortality were 33.7 % and 31.9 % respectively. There was an observed increase in the cumulative incidence of 30-/60-day mortality with higher DAR levels (log-rank test, P < 0.001). After accounting for other variables, the results from multivariable Cox proportional hazards analyses demonstrated that DAR independently predicted hospital death [HR (95%CI): 1.419 (1.205-1.670); P < 0.001] and ICU death [HR (95%CI): 1.437 (1.219-1.693); P < 0.001].

The DAR was found to be an independent predictor of all-cause mortality in critically ill patients with sepsis.