In comparison to mature platelets, reticulated platelets (RPs) are newly released from the bone marrow and exhibit a larger size, higher reactivity, and a greater quantity of RNA, and can be an agile indicator of platelet turnover. The transcriptome associated with platelet function is significantly upregulated in RPs, which is a possible explanation for RPs intrinsic hyper-reactivity. We presented a comprehensive overview of the detection techniques for RPs. Current methods to quantify RPs in clinical routine are flow cytometry and fully automated hematology analyzers (Sysmex-XE/XN, Abbott, ADVIA, Mindray), which make the detection of RPs simpler, faster and more affordable. The proportion of RPs increased in the circulation has potential diagnostic and prognostic values in multiple clinical settings (risk stratification in cardiovascular diseases, the effect on antiplatelet drugs, differential diagnosis of thrombocytopenia, monitor platelet recovery after bone marrow or stem cell transplantation, and other diseases). There have been several studies focusing on RPs in recent years, particularly in cardiovascular disease and thrombocytopenia. In this review we summarizes the current study with regard to RPs and discuss their likely contribution in clinical routine.

The elderly population, who have increased susceptibility to severe outcomes, have been particularly impacted by the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to a global health crisis. However, definitive parameters or mechanisms underlying the severity of COVID-19 in elderly people remain unclear. Thus, this study seeks to elucidate the mechanism behind the increased vulnerability of elderly individuals to severe COVID-19. We employed an aged mouse model with a mouse-adapted SARS-CoV-2 strain to mimic the severe symptoms observed in elderly patients with COVID-19. Comprehensive analyses of the whole lung were performed using transcriptome and proteome sequencing, comparing data from aged and young mice. For transcriptome analysis, bulk RNA sequencing was conducted using an Illumina sequencing platform. Proteomic analysis was performed using mass spectrometry following protein extraction, digestion, and peptide labelling. We analysed the transcriptome and proteome profiles of young and aged mice and discovered that aged mice exhibited elevated baseline levels of inflammation and tissue damage repair. After SARS-CoV-2 infection, aged mice showed increased antiviral and inflammatory responses; however, these responses were weaker than those in young mice, with significant complement and coagulation cascade responses. In summary, our study demonstrates that the increased vulnerability of the elderly to severe COVID-19 may be attributed to an attenuated antiviral response and the overactivation of complement and coagulation cascades. Future research on antiviral and inflammatory responses is likely to yield treatments that reduce the severity of viral respiratory diseases in the elderly.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, leading to an Omicron outbreak in Shanghai in mid-December after adjustments to the Coronavirus Disease 2019 (COVID-19) control strategy. To investigate the impact of COVID-19 infection among hypothyroid patients, we gathered data on the hypothyroid outpatients with COVID-19 infection during this time at the Thyroid Disease Center (TDC) of Shanghai Central Hospital. Patients were divided into two groups based on whether their hypothyroidism was caused by Hashimoto's Thyroiditis (HT): the HT and the non-HT group. We assessed the differences between pre-infection and clinical follow-up at one month (day (D) 30) and three months (D90) after COVID-19 infection. In HT group, thyroid-stimulating hormone (TSH) levels decreased significantly compared to pre-infection levels (p = 0.013), while free triiodothyronine (FT3) levels increased at D90 compared to both D30 post-infection and pre-infection levels (p < 0.001 and p = 0.005). Hemoglobin levels also increased after COVID-19 infection (p = 0.033). For non-HT patients, FT3 levels increased at D30 compared to pre-infection levels (p = 0.017). Moreover, inactivated SARS-CoV-2 vaccination can preserve thyroid function stability in patients with hypothyroidism.

Programmed cell death (PCD) plays a key role in the progression of coronavirus disease 2019 (COVID-19). However, PCD-relevant biomarkers have not been fully discovered. The aim of this study was to explore the PCD-relevant biomarkers for the treatment and prevention of COVID-19.

Bioinformatic analyses were performed to explore the clinical relevant PCD genes with differential expression (DE) in COVID-19 compared with matched controls. PPI network was used for hub genes screening and machine learning methods were employed for filtering feature genes. The biomarker genes were screened by Venn diagram. The correlations between biomarkers with clinical features and immune microenvironment were further explored. Biomarker validation was performed in clinical samples by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR).

In total, 118 clinically relevant and PCD associated differential expressed genes (DEGs) were screened, which were mainly related with apoptosis related pathways, among which six biomarkers (Cyclin B1 (CCNB1), cyclin-dependent kinase 1 (CDK1), interferon regulatory factor 4 (IRF4), lipoteichoic acid (LTA), matrix metallopeptidase 9 (MMP9) and Oncostatin M (OSM)) were identified. The excellent or good diagnostic performance of biomarkers was determined by receiver operating characteristic (ROC) curve analysis. The biomarkers showed diverse correlations with clinical indicators, such as age, sex and Intensive Care Unit (ICU) admission. Total 14 types of immune cells exerted differential infiltration between COVID-19 and controls. Biomarkers were correlated with immune cells at varying levels. COVID-19 was classified in three clusters, which showed differential expression of biomarker genes and significant associations with clinical information, such as sex, age and ICU admission. The DEGs of biomarkers were determined in COVID-19 patients relative to controls.

The six biomarkers (CCNB1, CDK1, IRF4, LTA, MMP9 and OSM) can be served as the biomarkers for the treatment and prevention of COVID-19.

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone significant genomic mutations, contributing to resistance against existing 2019 coronavirus disease (COVID-19) treatments. In a previous study, we identified N-0385, a potent host-directed inhibitor of transmembrane serine protease 2 (TMPRSS2), which has therapeutic efficacy towards SARS-CoV-2 infection. However, in further evaluation of its preclinical druggability, N-0385 displayed unfavorable pharmacokinetic properties, including high bioavailability (99 %) following intranasal (IN) administration. This can lead to substantial systemic exposure and potential adverse effects due to off-target interactions. Here, we designed a library of peptidomimetic compounds with P3 site modifications on an optimized scaffold. We sought to maintain sub-nanomolar potency against TMPRSS2 (Kis < 2 nM), reduce pseudovirus infection, while addressing the lack of selectivity and excessive lung uptake. Notably, inhibitor 9, which contains Asp at the P3 position, achieved a two-fold increase in TMPRSS2 inhibitory potency (Ki = 0.13 ± 0.03 nM), a >700-fold selectivity over Factor Xa (FXa), and showed superior selectivity against other proteases (matriptase, transmembrane serine protease 6 (TMPRSS6), thrombin, furin, and tPA). Despite concerns about the role of FXa in the coagulation cascade, compound 9 had no impact on coagulation or thrombolysis 2 h after in vitro treatment. In the air-liquid interface (ALI) model of the lung epithelium, compound 9 displayed a 1.5-fold decrease in permeability compared to N-0385 and demonstrated sustained stability in lungs (11 h) and plasma (13 h). Taken together, our data demonstrate that continued optimization of this type of inhibitors will lead to improved therapeutics for the treatment of SARS-CoV-2 infection by IN administration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can have a serious course with many complications, especially in immunocompromised individuals. In such persons, other latent virus infections may contribute to disease pathology, in particular viruses which infect immune cells such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV).

In this study, serology-based assays were conducted to analyse antibody responses to SARS-CoV-2 spike protein (SP), EBV Epstein-Barr nuclear antigen (EBNA)-1 and CMV phosphoprotein (pp)52 in naturally SARS-CoV-2-infected individuals, non-infected healthy controls (HCs) and vaccinated healthy controls (VHCs) to identify an association between SARS-CoV-2 antibodies and EBV and CMV antibodies in order to determine whether latent EBV and CMV infected individuals are more prone to become infected with SARS-CoV-2. Moreover, SARS-CoV-2, EBV, and CMV antibody responses were characterized in serum from patients with relapsing-remitting multiple sclerosis (RRMS), a chronic inflammatory disease strongly associated with EBV infections, to determine whether the serologic virus antibody profile varies in immunocompromised RRMS individuals upon SARS-CoV-2 vaccinations compared to VHCs.

Significantly elevated SP IgG, IgM and IgA levels were identified in SARS-CoV-2-infected immunocompetent individuals when compared to non-infected HCs. However, no correlation was found to serum antibodies between SARS-CoV-2, EBV, and CMV in individuals infected with SARS-CoV-2 and in VHCs, suggesting that latent infections with neither EBV nor CMV associates to SARS-CoV-2 infection. Moreover, no significant difference in SP IgG, IgA and IgM levels was observed between vaccinated RRMS patients and VHCs, indicating that the immune system of immune deficient RRMS patients and VHCs respond identical to SARS-CoV-2 vaccinations.

Collectively, SARS-CoV-2 SP antibody levels reflect the vaccination and infection history and do not associate with EBV and CMV serostatus.

Vitamin D receptor (VDR), influenced by gene polymorphisms like FokI, may affect susceptibility to infections, including coronavirus disease 2019 (COVID-19). Since studies in children are limited, we aimed to analyze the correlation between the VDR FokI variant and both the incidence and severity of COVID-19 in Egyptian children.

Seventy-seven COVID-19-positive and 107 COVID-19-negative pediatric patients were included. Participants' serum 25(OH)D levels, inflammatory biomarkers, and demographics were evaluated. Real-time polymerase chain reaction (PCR) was used for genotyping the VDR FokI (rs2228570) polymorphism.

Absolute lymphocyte count (ALC) was significantly lower in COVID-19 patients than in controls, while interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and D-dimer were significantly higher (all p < 0.001). Vitamin D insufficiency was significantly more common in COVID-19 cases (18.2 % versus 3.7 %, p = 0.002). Male sex, increased tumor necrosis factor-alpha (TNF-α), and CRP were significantly associated with severe COVID-19 (p = 0.032, 0.029, < 0.001, respectively). The FokI TT genotype in codominant and recessive models and the T allele in the multiplicative model were significantly correlated with 2.4, 3.0, and 1.8 folds increased COVID-19 risk (p = 0.043, < 0.001, and 0.004, respectively). However, VDR FokI variants did not significantly associate with severe COVID-19.

The T allele and TT genotype of the FokI variant in the VDR gene increase susceptibility to COVID-19 but not its severity in Egyptian children. Additional research is required to validate the potential role of vitamin D and its receptor polymorphism in COVID-19.

SARS-CoV-2, the third major coronavirus of the 21st century, causing COVID-19 disease, profoundly impacts public health and workforces worldwide. Identifying individuals at heightened risk of SARS-CoV-2 infection is crucial for targeted interventions and preparedness. This study investigated 35 SNVs within viral infection-associated genes in SARS-CoV-2 patients and uninfected controls from the Basque Country (March 2020-July 2021). Its primary aim was to uncover genetic markers indicative of SARS-CoV-2 susceptibility and explore genetic predispositions to infection. Association analyses revealed previously unreported associations between SNVs and susceptibility. Haplotype analyses uncovered novel links between haplotypes and susceptibility, surpassing individual SNV associations. Descriptive modelling identified key susceptibility factors, with rs11246068-CC (IFITM3), rs5742933-GG (ORMDL1), rs35337543-CG (IFIH1), and GGGCT (rs2070788, rs2298659, rs17854725, rs12329760, rs3787950) variation in TMPRSS2 emerging as main infection-susceptibility indicators for a COVID-19 pandemic situation. These findings underscore the importance of integrated SNV and haplotype analyses in delineating susceptibility to SARS-CoV-2 and informing proactive prevention strategies. The genetic markers profiled in this study offer valuable insights for future pandemic preparedness.

COVID-19 patients face an increased risk of thromboembolic complications, yet the exact pathophysiological role of platelets in the disease remains unclear. Considering the multifaceted nature of COVID-19 symptoms, including platelet hyperactivation and inflammation, the development of compounds that simultaneously target both represents a promising therapeutic strategy. The monoterpene 1.8-cineole (CNL-1976) is known for its anti-inflammatory and anti-aggregatory effects. Thus, understanding the mechanism behind platelet hyperactivation and the effect of 1.8-cineole during COVID-19 is crucial when aiming for a reduction of disease severity. In this study, we investigated the mechanism of platelet activation triggered by the SARS-CoV-2 S1 spike protein (S1). Utilizing S1-coupled beads, we discovered that platelet activation and aggregation were dependent on plasma components, particularly S1-specific IgG antibodies. The formation of immune complexes through IgG binding to S1 facilitated the crosslinking of the platelet expressed FcγRIIa receptor, initiating platelet activation and aggregation, as well as formation of platelet-leukocyte aggregates (PLAs). Importantly, treatment with 1.8-cineole significantly inhibited S1-bead-induced platelet activity and PLA formation. These findings strongly suggest that antibody-mediated platelet activation via FcγRIIa directly contributes to the well-recognized prothrombotic environment during COVID-19. Moreover, our data indicate that 1.8-cineole can serve as a potential therapeutic compound, alleviating platelet-driven thromboinflammatory complications associated with COVID-19 and post-acute sequelae of SARS-CoV-2 (PASC).

Inborn errors of immunity (IEI) are congenital disorders of the immune system. Due to impaired immune system, they are at a higher risk to develop a more severe COVID-19 course compared to general population.

Herein, we aimed to systematically review various aspects of IEI patients infected with SARS-CoV-2. Moreover, we performed a meta-analysis to determine the frequency of COVID-19 in patients with different IEI.

Embase, Web of Science, PubMed, and Scopus were searched introducing terms related to IEI and COVID-19.

3646 IEI cases with a history of COVID-19 infection were enrolled. The majority of patients had critical infections (1013 cases, 27.8%). The highest frequency of critical and severe cases was observed in phenocopies of IEI (95.2%), defects in intrinsic and innate immunity (69.4%) and immune dysregulation (23.9%). 446 cases (12.2%) succumbed to the disease and the highest mortality was observed in IEI phenocopies (34.6%). COVID-19 frequency in immunodeficient patients was 11.9% (95% CI: 8.3 to 15.5%) with innate immunodeficiency having the highest COVID-19 frequency [34.1% (12.1 to 56.0%)]. COVID-19 case fatality rate among IEI patients was estimated as 5.4% (95% CI: 3.5-8.3%, n = 8 studies, I2 = 17.5%).

IEI with underlying defects in specific branches of the immune system responding to RNA virus infection experience a higher frequency and mortality of COVID-19 infection. Increasing awareness about these entities and underlying genetic defects, adherence to prophylactic strategies and allocating more clinical attention to these patients could lead to a decrease in COVID-19 frequency and mortality in these patients.

Probiotics and prebiotics have been suggested as natural agents against viral infections and dysbiosis and may encourage clinical applications. This review aims to analyze the main and recent advances related to viral infections such as Covid-19 and its gastrointestinal complications, antiviral immunity generated and possible preventive role that probiotics and/or prebiotics can play in controlling and promoting antiviral immunity. The literature search was performed through a critical analysis of relevant publications reported in PubMed and Scopus databases on clinical trials and assays conducted in vitro on colon cells and in vivo on mice. Some studies using probiotics and prebiotics for the prevention of viral infection in different age groups are discussed. Covid-19 patients have been shown to suffer from gastrointestinal complications in addition to respiratory symptoms due to interactions between the respiratory system and the gastrointestinal tract infected with SARS-CoV-2. Unfortunately, therapies used to prevent (or treat) symptoms of Covid-19 have proven to be of limited effectiveness. In addition, the lack of access to coronavirus vaccines around the world and vaccine hesitancy continue to hamper control of Covid-19. It is therefore crucial to find alternative methods that can prevent disease symptoms. Evidence-based efficacy of certain probiotics (Lactobacillus and Bifidobacterium) that may be useful in viral infections was shown with immunomodulatory properties (pro-inflammatory mediators reduction), promoting antiviral immunity (antibodies production, virus titers) and controlling inflammation (anti-inflammatory effect), as well as viral clearance and antimicrobial potential against opportunistic bacteria (anti-dysbiosis effect). But, available data about clinical application of probiotics in Covid-19 context remain limited and relevant scientific investigation is still in its early stages. Also, evidence for prebiotics potential in this field is limited, since the exact mechanism involved in systemic immune modulation by these compounds is till now unknown. Thus, further research is necessary to explore in the viral infection context the mechanism by which gut and lung interact in the presence of probiotics and prebiotics through more animal and clinical experiments.

The COVID-19 disease has spread rapidly across the world within just six months, affecting 169 million people and causing 3.5 million deaths globally (2021). The most affected countries include the USA, Brazil, India, and several European countries such as the UK and Russia. Healthcare professionals face new challenges in finding better ways to manage patients and save lives. In this regard, more comprehensive research is needed, including genomic and proteomic studies, personalized medicines and the design of suitable treatments. However, finding novel molecular entities (NME) using a standard or de novo strategy to drug development is a time-consuming and costly process. Another alternate strategy is discovering new therapeutic uses for old/existing/available medications, known as drug repurposing. There are a variety of computational repurposing methodologies, and some of them have been used to counter the coronavirus disease pandemic of 2019 (COVID-19). This review article compiles recently published data on the origin, transmission, pathogenesis, diagnosis, and management of the coronavirus by drug repurposing and vaccine development approach. We have attempted to screen probable drugs in clinical trials by using literature survey. This systematic review aims to create priorities for future research of drugs repurposed and vaccine development for COVID-19.

The aim of this study was to evaluate the incidence, severity, duration of oral manifestations in individuals with Coronavirus Disease 2019 (COVID-19) and the association of these manifestations with the severity of COVID-19 and the patient's oral hygiene.

This study included 820 patients with confirmed COVID-19. A questionnaire form including oral hygiene habits, the severity of Covid-19, the presence, severity and durations of oral manifestations was prepared, and a web-based survey was performed using Google-forms. Obtained data was analysed with Pearson chi-square and Fisher's exact tests with statistical significance set at P < 0.05.

The most commonly reported manifestations were taste dysfunction (63.4%), xerostomia (59.9%), halitosis (31.1%), dysphagia (27.8%), hypersensitive teeth (27.2%) and gingival bleeding (14.3%). The incidence of the oral manifestations was found significantly associated with severity of COVID-19 (P = 0.000 V = 0.151), presence of systemic diseases (P = 0.034, V = 0.074) and age (P = 0.023, V = 0.099). Tooth brushing decreased the incidence of aphthous like lesions of tongue during Covid-19 (p < 0.05).

Maintenance of oral hygiene was associated with a reduced incidence of aphthous-like lesions, underscoring the protective role of routine oral care. These findings highlight the need to integrate oral health assessment and hygiene education into COVID-19 management protocols, which may also be important for potential future pandemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced impaired antiviral immunity and excessive inflammatory responses cause lethal pneumonia. However, the in vivo roles of key pattern recognition receptors that elicit protective antiviral and fatal inflammatory responses, specifically in the lungs, are not well described. Coronaviruses possess single-stranded RNA genome that activates TLR7/8 to induce an antiviral interferon (IFN) and robust inflammatory cytokine response. Here, using wild-type and TLR7-deficient (TLR7-/-) mice infected with mouse-adapted SARS-CoV-2 (MA-CoV-2), we examined the role of TLR7 in the lung antiviral and inflammatory response and severe pneumonia. We showed that TLR7 deficiency significantly increased lung virus loads and morbidity/mortality, which correlated with reduced levels of type I IFNs (Ifna/b), type III IFNs (Ifnl), and IFN-stimulated genes (ISGs) in the lungs. A detailed evaluation of MA-CoV-2-infected lungs revealed increased neutrophil accumulation and lung pathology in TLR7-/- mice. We further showed that blocking type I IFN receptor (IFNAR) signaling enhanced SARS-CoV-2 replication in the lungs and caused severe lung pathology, leading to 100% mortality compared to infected control mice. Moreover, immunohistochemical assessment of the lungs revealed increased numbers of SARS-CoV-2 antigen-positive macrophages, pneumocytes, and bronchial epithelial cells in TLR7-/- and IFNAR-deficient mice compared to control mice. In summary, we conclusively demonstrated that despite TLR7-induced robust lung inflammation, TLR7-induced IFN/ISG responses suppress lung virus replication and pathology and provide protection against SARS-CoV-2-induced fatal pneumonia. Additionally, given the similar disease outcomes in control, TLR7-/-, and IFNAR-deficient MA-CoV-2-infected mice and coronavirus disease 2019 (COVID-19) patients, we propose that MA-CoV-2-infected mice constitute an excellent model for studying COVID-19.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is caused by a delicate balance between a strong antiviral and an exuberant inflammatory response. A robust antiviral immunity and regulated inflammation are protective, while a weak antiviral response and excessive inflammation are detrimental. However, the key host immune sensors that elicit protective antiviral and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge are poorly defined. Here, we examined the role of viral RNA-mediated TLR7 activation in the lung antiviral and inflammatory responses in SARS-CoV-2-infected mice. We demonstrate that TLR7 deficiency led to a high rate of morbidity and mortality, which correlated with an impaired antiviral interferon (IFN)-I/III response, enhanced lung virus replication, and severe lung pathology. Furthermore, we show that blocking IFN-I signaling using anti-IFN receptor antibody promoted SARS-CoV-2 replication in the lungs and caused severe disease. These results provide conclusive evidence that TLR7 and IFN-I receptor deficiencies lead to severe disease in mice, replicating clinical features observed in COVID-19 patients.

Infection by the SARS-CoV-2 virus can cause coronavirus disease 2019 (COVID-19) and can also exacerbate the symptoms of Kawasaki disease (KD), an acute vasculitis that mostly affects children. This study used bioinformatics and machine learning to examine similarities in the molecular pathogenesis of COVID-19 and KD.

We first identified disease-associated modules in KD using weighted gene co-expression network analysis. Then, we determined shared differentially expressed genes (DEGs) in training datasets for KD (GSE100154) and COVID-19 (GSE225220), performed functional annotation of these shared DEGs, and used Cytoscape plug-ins (MCODE and Cytohubba) to characterize the protein-protein interaction (PPI) network and identify the hub genes. We performed Least Absolute Shrinkage and Selection Operator(LASSO) regression and receiver operating characteristic (ROC) curve analysis to identify the most robust markers, validated these results by analysis of two other datasets (GSE73461 and GSE18606), and then calculated the correlations of these key genes with immune cells.

This analysis identified 26 shared DEGs in COVID-19 and KD. The results from functional annotation showed that the shared DEGs primarily functioned in immune responses, the formation of neutrophil extracellular traps, and NOD-like receptor signaling pathways. There were three key genes (PGLYRP1, DEFA4, RETN), and they had positive correlations with monocytes, M0 macrophages, and dendritic cells, which function as immune infiltrating cells in KD.

The potential immune-associated biomarkers (PGLYRP1, DEFA4, RETN) along with their shared pathways, hold promise for advancing investigations into the underlying pathogenesis of KD and COVID-19.

to evaluate the performance of qSOFA in identifying deterioration in patients with COVID-19.

retrospective cohort study conducted between February and August 2020 in the Emergency Department of a private hospital, involving 813 adults. The variables studied included sociodemographic data, clinical characteristics, deterioration, qSOFA on admission and before the event, and outcomes. The performance of qSOFA at both moments was analyzed using the area under the ROC curve.

the average age was 69 years. There was a predominance of men (61.5%), white (97.2%), catholic (73.7%), married (89.6%) and employed (66%). Comorbidities were present in 69.7%, and 58.8% were classified as "urgent" upon admission. The most frequent deterioration was respiratory failure (16.7%), and the outcome was discharge (68%). Patients with positive qSOFA on admission had a higher percentage of respiratory failure, cardiopulmonary arrest, and "very urgent" risk classification, and those with negative qSOFA showed a higher percentage of discharge (p< 0.0001). Upon admission, qSOFA showed 66% sensitivity and 55% specificity, and prior to the event it showed 48% sensitivity and 88% specificity for identifying clinical deterioration. Patients with positive qSOFA on admission were 350 times more likely to experience deterioration.

qSOFA showed low sensitivity for identifying deterioration at both moments and high specificity before the event.

Being widespread across the globe, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps evolving and generating new variants and continuously poses threat to public health, especially to the population with chronic comorbidities. Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019 (COVID-19). Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential. Here, in this study, we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus (db/db), and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters. SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters. Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters, and may induce serious complications such as diabetic kidney disease and cardiac lesions. Our findings demonstrated that despite the decreased respiratory pathogenicity, the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters, suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected. This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes. It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.

It is argued that commensal bacteria in the upper respiratory tract (URT) protect against pathogen colonization and infection, including respiratory viruses. Given that the microbiome can mediate immune modulation, a link between the URT microbiome (URTM) and COVID-19 susceptibility and severity is expected. This 16S metagenomics cross-sectional study assessed URTM composition, metabolic prediction, and association with laboratory biomarkers in non-COVID-19 pneumonia (NO-CoV), moderate (M-CoV), severe (S-CoV) COVID-19 patients, as well as COVID-19-negative, asymptomatic (NC) patients. The S-CoV group exhibited reduced URTM diversity, primarily due to a decreased abundance of eubiotic taxa. Some of these taxa (e.g., Haemophilus sp., Neisseria sp.) were also associated with inflammatory biomarkers. Multiple metabolic pathways (e.g., short-chain fatty acids, vitamin B12) linked to immune response, antiviral activity, and host susceptibility showed decreased abundance in S-CoV. These pathways could suggest potential alternatives for the therapeutic arsenal against COVID-19, providing reassurance about the progress in understanding and treating this disease.

The efficacy of clinical drugs for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains suboptimal. Phillyrin (PHN), a compound derived from Forsythia, is believed to alleviate sepsis-related ALI/ARDS; however, its mechanisms are not fully elucidated. In this study, we screened 8331 target genes associated with ALI/ARDS from public databases and identified six hub genes relevant to PHN treatment: AKT1, GSK-3β, PPP2CA, PPP2CB, PPP2R1A, and AR. Receiver operating characteristic analysis and single-cell sequencing analysis revealed the expression of AKT1, GSK-3β, PPP2CA, PPP2CB, and PPP2R1A were markedly elevated. Molecular docking and dynamics simulations indicated that PHN forms a structurally stable complex with glycogen synthase kinase-3β (GSK-3β). Mendelian randomization analyses suggested that PHN, as a potent GSK-3β inhibitor, may promote M2 macrophage polarization and reduce neutrophil recruitment. We validated these findings through in vivo and in vitro experiments, demonstrating that PHN lowers iNOS levels and raises MMR levels by downregulating GSK-3β mRNA expression and protein activity during lipopolysaccharide (LPS)-induced macrophage inflammation. Additionally, PHN inhibited GSK-3β mRNA expression and protein activity, reducing NF-κB-p65 nuclear translocation in LPS-induced zebrafish inflammation and mice ALI. This inhibition decreased levels of TNF-α and IL-6, increased IL-10 levels, promoted M2 macrophage polarization, suppressed neutrophil recruitment, and ultimately ameliorated ALI/ARDS. In conclusion, our results indicate that PHN effectively alleviates LPS-induced ALI/ARDS by suppressing GSK-3β signaling.

Despite global efforts to mitigate COVID-19 infection through vaccination and therapeutic interventions, morbidity and mortality rates continued at variable rates. Although mortality risk and clinical features of COVID-19 are well-documented, recovery patterns and prognostic factors post-admission remain inconclusive, particularly in resource-limited settings like Ethiopia. This systematic review and meta-analysis (SRM) aimed to estimate the pooled incidence rate of recovery and predictors among hospitalized COVID-19 patients in Ethiopia.

We searched (N = 1,191) articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline from PubMed/MEDLINE (N = 755), Scopus (N = 137), Web of Science (N = 84), Science Direct (N = 148), Cochran (N = 25), and Google Scholar searching (N = 42) from December 2019 to February 2024. The data were extracted using a Microsoft Excel spreadsheet and exported to Stata TM version 17.0 for further analysis. The Article quality was assessed using the Joanna Briggs Institute checklist. The pooled incidence rate of recovery was estimated using a weighted inverse variance random-effects meta-regression. Heterogeneity among studies was evaluated using the I2 statistic. Subgroup analyses and sensitivity tests were also conducted to explore publication bias. This file is registered in international Prospero with ID (CRD42024518569).

Sixteen (N = 16) published studies with 7,676 hospitalized COVID-19 patients were included in the final report. The mean age of participants ranged from 29 (± 17) to 57.5 (± 3) years, with male patients constituting the largest proportion of participants, 4,491(58.5%). During recovery screening, 6,304(82.21%) cases were discharged as improved, 159 (2.1%) attriters, and 818 (10.6%) died during inpatient treatment. The pooled incidence of recovery, mortality, and attrition rates were found to be 82.32% (95% CI: 78.81-85.83; I2 = 94.8%), 14.3% (I2 = 98.45%), and 2.7% (I2 = 81.34%), respectively. Incidence of recovery rate varied across regions and epidemic phases, with the highest rate observed in Addis Ababa (89.94%, I2 = 78.33%) and the lowest reported in the Tigray region (59.7%, I2 = 0.0%). Across epidemic phases, the recovery rate was 88.05% (I2 = 29.56%) in Phase II, 84.09% (I2 = 97.57%) in Phase I, and 78.92% (I2 = 96.9%) in Phase III, respectively. Factors included being aged 15-30 years (pooled OR = 2.01), male sex (pooled OR = 1.46), no dyspnea (pooled OR = 2.4; I2 = 79%), and no baseline comorbidities (pooled OR = 1.15; I2 = 89.3%) were predictors for recovery. CONCLUSION AND RECOMMENDATION: In Ethiopia, more than eight out of ten hospitalized COVID-19 patients recovered after inpatient treatment. However, the incidence of recovery rates varied significantly across epidemic phases, study settings, and regions. Factors including younger age, male sex, no dyspnea (shortness of breathing), and no underlying comorbidity heightened recovery. It is highly recommended those inpatients cares should focus on high-risk groups (older adults) and implement standardized treatment protocols in each study setting. Regions with lower recovery rates need aid in logistical support and training for healthcare providers.

Rhabdomyolysis can occur due to many traumatic and nontraumatic causes. Rhabdomyolysis has been reported in new type of coronavirus disease (COVID-19) cases. The aim of our study was to examine the effects of rhabdomyolysis on mortality and renal outcomes in patients hospitalized in our hospital's COVID-19 wards. In our single-center and retrospective study, we included patients who were admitted with a diagnosis of COVID-19 by a thorax-computed tomography finding who were older than 18 years of age and with a measured creatinine kinase (CK) > 1000 U/L on any day of hospitalization. The same number of patients hospitalized in COVID-19 services with CK < 1000 U/L and with similar gender and age were determined as the control group. We analyzed the data of 2065 patients, and compared 154 patients in the rhabdomyolysis group (group 1) and 154 patients in the control group (group 2). Acute kidney injury (AKI) (44.2% vs 21.4%; P < .001), intensive care unit (ICU) admissions (53.2% vs 13.6%; P < .001), intubation (75.6% vs 23.8%; P < .001), mortality (36.4% vs 3.2%; P < .001) and the need for dialysis (3.9% vs 0.6%; P = .005) were seen more in the rhabdomyolysis group. When that group was divided into the early rhabdomyolysis group (group 1a), where the CK value reached its highest value in ≤3 days, and the late rhabdomyolysis group (group 1b), where it was ≥ 4 days, AKI (29.7% vs 65.1%; P < .001), ICU (35.2% vs 79.4%; P < .001), intubation (56.2% vs 88%; P = .001), mortality (18% vs 61.9%; P < .001), and dialysis (1.1% vs 7.9%; P = .031), the results were higher in the group 1b. The available data suggest that rhabdomyolysis seen in COVID-19 patients is not a direct predictor of mortality and poor renal outcomes, but is a secondary outcome to multiple-organ failure caused by worsening clinical status.

Coronavirus disease identified in 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2, had a global impact on human health and the economy. The aim of this study was to quantify cytokines, chemokines, and acute phase proteins in the plasma of patients with COVID-19 to elucidate potential biomarkers to inform prognostic and treatment decisions. Clustering analysis using the K-prototypes method identified underlying biological patterns in patients with COVID-19. The penalized multinomial logistic regression analysis identified two comorbidities (hypertension, congestive heart failure) and thirteen analytes as potential risk factors for COVID-19 progression with 88.2% accuracy. Based on a patient's age, high concentrations of interleukin (IL)-6, monocyte chemoattractant protein-1, and pentraxin 3 were important biomarkers for lethal COVID-19. Decreased concentrations of interferon gamma-induced protein-10, IL-10, and soluble tumor necrosis factor receptor I were found to be associated with mild COVID-19, while increasing concentrations of these analytes could be used to predict COVID-19 severity.

Various comorbidities are known to exacerbate the risk of surgical mortality with COVID-19 infection. The effect of HIV infection on surgical mortality in the context of COVID-19 has also not been investigated. The aim of our study was to investigate the influence of HIV status on mortality in surgical patients admitted during the COVID-19 pandemic in Johannesburg, South Africa.

We reviewed records of patients who were admitted and underwent surgery during the COVID-19 pandemic and died. Data regarding perioperative COVID-19 infection, risk factors, comorbidities, mortality preventability, and contributing factors were extracted. Logistic regression was used to analyze comorbidities associated with COVID-19 infection among surgical mortalities.

A total of 404 records of mortalities were found and 25% (82/404) tested positive for COVID-19. 40% Of the mortalities were either potentially preventable or preventable. Comorbidities in patients who were COVID-19-positive surgical mortalities compared to their negative counterparts included smoking in 35% versus 4%, chronic obstructive pulmonary disease (COPD) in 20% versus 3%, and diabetes mellitus in 23% versus 13%, respectively. The odds of being COVID-19 positive in surgical mortalities with hypertension, smoking, and COPD were 1.96 times [OR = 1.96, 95% CI (1.06, 3.59)], 7.78 times [OR = 7.78, 95% CI (3.45, 18.35)], and 3.09 times [OR = 3.09, 95% CI (1.08, 8.95)], respectively. 55% of COVID-19-positive patients who died were HIV positive compared to 31% among the COVID-19-negative group. 26% of HIV-positive patients were on anti-retroviral treatment (ART). 22% of HIV-/COVID-19-coinfected surgical mortalities were not on antiretroviral treatment compared to 9% in the HIV-positive and COVID-19-negative groups. The odds of COVID-19 infection in surgical mortalities who were HIV positive and not on ART was 3.10 [95% CI (1.55, 6.11)].

The rate of COVID-19 infection was higher in HIV-positive patients who died, especially if they were not on ART. Smoking, COPD, and hypertension imparted the largest risk on COVID-19 infection in cases of surgical mortality. These comorbidities likely superimpose the pathological effects of COVID-19 infection, worsening surgical prognosis.

When the coronavirus case was originally reported in Wuhan, China, in December 2019, it quickly spread throughout the world and became a global public health problem. Evidence of the admission and outcomes of coronavirus disease among patients with chronic obstructive pulmonary disease (COPD) has not been reported in Africa. Consequently, this research protocol uses a systematic review and meta-analysis of the admission and outcomes of COVID-19 in patients with COPD in Africa. All observational studies published in the English language and reporting on the prevalence, admission and outcomes of COVID-19 among patients with COPD in Africa will be included. A search strategy will be implemented using electronic databases and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol recommendations. The findings of this review will be reported to health program designers, decision-makers and healthcare providers.

The emergence of Rocahepevirus ratti genotype 1 (rat hepatitis E virus; rat HEV) in humans presents an unprecedented threat; however, the risk of rat HEV transmission to humans is not well understood. Here, we report the "Distinguishing Antibody Response Elicitation (DARE)" method, which distinguishes exposure to rat HEV. We use four study sets from China for large-scale population analysis: set 1 (hospital visit) and set 3 (ALT abnormality) from Yunnan province, a biodiversity hotspot, and set 2 (received physical examination) and set 4 (ALT abnormality) from Jiangsu province, a non-hotspot control region. rat HEV exposure risk is significantly higher in Yunnan, with 21.97% (190 of 865) in set 1 and 13.97% (70 of 501) in set 3, compared to 0.75% (9 of 1196) in Jiangsu's set 2. Six spillover infections for rat HEV are identified in set 1, with one case of abnormal ALT. The rat-1d strains carried by rats are closely related to those human infections. Our study reveals the substantial spillover burden posed by rat HEV in biodiversity hotspots and highlights the utility of DARE method for proactive surveillance of public health emergencies.

Acute surgical abdomen is characterized by intense, sudden abdominal pain due to intra-abdominal conditions requiring prompt surgical intervention. The coronavirus disease 2019 (COVID-19) pandemic has led to various complications related to the disease's complex pathophysiological mechanisms, hence the hypothesis of COVID-19-induced acute abdominal surgical pathologies. The connection between acute surgical abdomen and COVID-19 involves two primary mechanisms. First, there is the presence of angiotensin-converting enzyme 2 (ACE2) receptors in multiple abdominal organs. This facilitates the cytokine storm through direct viral injury and inflammation. Second, the hypercoagulable state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the thrombotic risk within abdominal vessels, which can subsequently lead to ischemia. ACE2 receptors are notably expressed in the gastric, duodenal, and rectal epithelium, with SARS-CoV-2 viral RNA and nucleocapsid proteins detected in these tissues. The inflammatory response results in significant endothelial damage, activating coagulation pathways that cause monocellular infiltration, lymphocytic inflammation, and uncontrolled coagulation. These findings highlight the need for further research to clarify how COVID-19 leads to acute abdominal pathologies. Understanding these mechanisms is vital for improving clinical management and patient outcomes during future health crises and in the aftermath of the pandemic.

Acute type A aortic dissection (ATAAD) is a deadly form of acute aortic syndrome which necessitates emergency surgical repair. Coronavirus disease-19 (COVID-19) pandemic has caused a significant impact on surgery globally. The influence of the COVID-19 pandemic on ATAAD patients undergoing surgical repair remains undetermined.

We conducted a systematic review and meta-analysis of studies comparing ATAAD patients undergoing aortic surgery before versus during the COVID-19 pandemic and literature review of published cases reporting COVID-19 patients undergoing surgical repair for ATAAD. PubMed, China National Knowledge Infrastructure, VIP, WANFANG, and SinoMed databases were searched for relevant studies and case reports till January 21st, 2023, and the database search was updated on January 3rd, 2024. Meta-analysis was performed by utilizing RevMan. Pooled odds ratio (OR) and 95% confidence interval (CI) were estimated for dichotomous data, and weighted mean difference (WMD) and 95% CI for continuous data, respectively. All P-values were 2-sided and statistical significance was defined as P < .05.

Meta-analysis of 5 included studies comparing ATAAD patients undergoing aortic surgery before versus during the COVID-19 pandemic demonstrated that, the patients in Group During-Pandemic (DP) were older than those in Group Before-Pandemic (BP; P = .005), and the body mass index of the patients in Group DP was lower than that of the patients in Group BP (P = .002), more patients in Group DP were smokers (P = .02). Meta-analysis also showed that, either the composite incidence of mortality and morbidities or individual morbidity was comparable between 2 groups, except that more patients in Group DP developed pneumonia (P = .05). Literature reviews of 24 published cases reporting COVID-19 patients undergoing surgical repair for ATAAD demonstrated that, twenty (83.3%) patients recovered well after aortic surgery and were finally discharged from hospital. Unfortunately, 4 patients died postoperatively, 3 due to multiple organ failure and one due to respiratory failure (RF). Reported postoperative complications included hypoxia, endotracheal re-intubation, RF, renal failure, coagulopathy, fever, multi-organ failure and shock.

The hospitalized outcomes of ATAAD patients undergoing surgical repair before versus during the COVID-19 were mostly comparable. ATAAD patients with concomitant COVID-19 infection who underwent emergent surgical repair had a high risk of mortality and morbidities.

The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SARS-CoV-2-induced inflammation and senescence remains unclear. Triggering receptors expressed on myeloid cell-1 (TREM-1) are myeloid cell receptors that amplify inflammation, described as a biomarker of the severity and mortality of COVID-19. This study investigated the composition and effects of macrophage-derived EVs stimulated by SARS-CoV-2 (MφV-EVs) on the recipient cell response. Our results, for the first time, show that SARS-CoV-2 stimulation modifies the cargo profile of MφV-EVs, enriching them with TREM-1 and miRNA-155 association, along with MMP-9 and IL-8/CXCL8. These EVs carry senescence-associated secretory phenotype (SASP) components, promote cellular senescence, and compromise antibacterial defenses upon internalization. Our findings provide evidence that MφV-EVs are key drivers of inflammation and immune dysfunction, underscoring their potential as therapeutic targets in COVID-19.

Machine learning models have been employed to predict COVID-19 infections and mortality, but many models were built on training and testing sets from different periods. The purpose of this study is to investigate the impact of temporality, i.e., the temporal gap between training and testing sets, on model performances for predicting COVID-19 infections and mortality. Furthermore, this study seeks to understand the causes of the impact of temporality.

This study used a COVID-19 surveillance dataset collected from Brazil in year 2020, 2021 and 2022, and built prediction models for COVID-19 infections and mortality using random forest and logistic regression, with 20 model features. Models were trained and tested based on data from different years and the same year as well, to examine the impact of temporality. To further explain the impact of temporality and its driving factors, Shapley values are employed to quantify individual contributions to model predictions.

For the infection model, we found that the temporal gap had a negative impact on prediction accuracy. On average, the loss in accuracy was 0.0256 for logistic regression and 0.0436 for random forest when there was a temporal gap between the training and testing sets. For the mortality model, the loss in accuracy was 0.0144 for logistic regression and 0.0098 for random forest, which means the impact of temporality was not as strong as in the infection model. Shapley values uncovered the reason behind such differences between the infection and mortality models.

Our study confirmed the negative impact of temporality on model performance for predicting COVID-19 infections, but it did not find such negative impact of temporality for predicting COVID-19 mortality. Shapley value revealed that there was a fixed set of four features that made predominant contributions for the mortality model across data in three years (2020-2022), while for the infection model there was no such fixed set of features across different years.

A detailed analysis was carried out on the impact of cardiovascular disease on the risk of death of patients hospitalized at a temporary hospital in Gdańsk during the third and fifth waves of the COVID-19 pandemic (in 2021 and 2022, respectively). Background/Objectives: The documentation of 1244 patients was analyzed, of which 701 were hospitalized in 2021 (the Delta variant) and 543 in 2022 (the Omicron variant). The aim of this study was to assess the risk of death of patients with COVID-19 depending on the co-existence of cardiovascular diseases. Methods: A model of logistic regression was used to identify the impact of the patients' age, the coexistence of cardiovascular disease, and the length of hospitalization on the risk of death. Results: In 2021, patients were younger (median of 66 years) than in 2022 (median of 74 years), the length of hospitalization was shorter in 2022 (9 days) than in 2021 (11 days), and there was a higher proportion of patients with cardiovascular and respiratory diseases and a medical history of cancer in 2022. The odds of death were also observed to be higher in older patients with cardiovascular disease, particularly those under 73 years of age. In older patients (over 73 years), the odds were paradoxically reduced. Conclusions: The age of the patient, cardiovascular disease, and duration of hospitalization affect the risk of death. The Delta variant (2021) was more virulent than Omicron (2022). Cardiovascular disease significantly increases the risk of death in patients with COVID-19. The comprehensive diagnosis and treatment of patients with these conditions may reduce mortality. Further studies are needed on the long-term effects of COVID-19 on the cardiovascular system.

Gastrointestinal (GI) manifestations have been reported as the most extra-pulmonary manifestations of coronavirus disease 2019 (COVID-19). Recognizing the various manifestations, especially as presenting symptoms of COVID-19 is of great importance. We aimed to investigate the GI and hepatic manifestations of COVID - 19 in children, determining the factors associated with the disease severity and prognosis related to GI symptoms.

In this retrospective study, children aged 1-month to 16-years who were admitted to Afzalipour Hospital in Kerman, Iran. for a period of one year (from October 2020 to October 2021) with the diagnosis of COVID-19 were included. The comparison of clinical symptoms and laboratory variables in the appendectomy and non-appendectomy groups were evaluated. Patients' information was extracted from the patient's medical record and analyzed in SPSS statistical. software.

A total of 163 patients (107 boy and 56 girls) with mean age of 4.35 ± 3.86 (range 0.08 to 16) years were included. The most frequent GI symptoms at the time of admission were watery diarrhea (46.6%), vomiting (45.4%), and abdominal pain (32.5%). There was no significant relationship between clinical symptoms and laboratory variables in the appendectomy and non-appendectomy groups, but the severity of COVID-19 was significantly associated with appendicitis (P = 0.03). There was no statistically significant relationship between liver enzyme levels and disease severity and pediatric intensive care unit admission.

Although most COVID-19 patients present with GI manifestations, we could not determine the relationship between GI and hepatic manifestations and disease severity in this study.

Not applicable.

Activities of Daily Living (ADL) are crucial for assessing older adult's ability to live independently. Physical exercise has a positive impact on ADL. During the COVID-19 pandemic, the reduction of social interaction and the limited use of exercise facilities led some older adults to reduce regular exercise and show more sedentary behavior. This study aimed to examine the influence of physical exercise on the Activities of Daily Living (ADL) among older adults during the COVID-19 pandemic.

Using the China Longitudinal Aging Social Survey (CLASS) data, propensity score matching (PSM) was performed on the sample, with the interaction between participation in physical exercise and observation year as the core independent variables, and instrumental activities of daily life (IADL) and basic activities of daily life (BADL) as the dependent variables for difference-in-differences (DID) regression analysis. Verify age heterogeneity through grouped regression, and use mediation effect analysis to examine the role of retirement.

In the context of COVID-19, participation in physical exercise had a negative impact on the IADL and BADL of older adults. The IADL and BADL of the older adults who participated in physical exercise were 0.189 and 0.119 units lower than those who did not participate in physical exercise. This negative impact also varied by age, for older adults aged 75 years and above, participation in physical exercise exerted a significant positive impact on both IADL and BADL. In contrast, among those under 75 years of age, no significant effects of physical exercise on IADL or BADL were detected. The analysis further revealed retirement status emerged as a significant masking variable that amplifies observed differences in ADL outcomes when controlled analytically.

During the pandemic, physical exercise still has a positive impact on the IADL and BADL of the older adults. The older adults aged 75 and above are more reliant on physical exercise to improve their IADL and BADL. Due to the survivor effect, the relative negative effect of retirement on the IADL and BADL of the older adults who engage in physical exercise is more pronounced.

The co-infection of COVID-19 with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is rare but can lead to severe outcomes, especially in diabetic patients with impaired immune function. CA-MRSA, especially PVL-positive strains, can exacerbate COVID-19 symptoms and drive rapid disease progression.

We present a case of a 53-year-old diabetic female patient with poor glycemic control, who was hospitalized with COVID-19 and rapidly progressed to severe pneumonia. Despite antiviral treatment with Paxlovid and dexamethasone, as well as antimicrobial therapy with piperacillin-tazobactam, her condition deteriorated, leading to respiratory failure requiring extracorporeal membrane oxygenation. A post-mortem sputum culture confirmed MRSA on the day following the patient's death.

This case underscores the critical need for screening and treating bacterial co-infections in COVID-19 management, particularly in immunocompromised hosts, due to the enhanced pathogenicity of CA-MRSA strains. Early recognition and appropriate antimicrobial therapy are essential in reducing the impact of such co-infections.

The Omicron subvariants of SARS-CoV-2 spread rapidly since 2021. Following China's relaxation of containment measures in December 2022, a surge in COVID-19 cases poses a public health threat. Early identification of elderly COVID-19 patients at death risk is crucial for optimizing treatment and resource use.

To develop a clinical score for predicting death risk in elderly COVID-19 patients at hospital admission, based on a cohort from the Second Hospital of Shandong University.

We established a retrospective cohort of hospitalized COVID-19 patients from November 1, 2022, to March 31, 2023. Cox regression identified prognostic factors, leading to the development of a nomogram-based prediction model and a clinical risk score. Patients were classified into low- and high-risk groups using optimal segmentation thresholds, with survival curves generated by the Kaplan-Meier method. An online risk calculator was developed to facilitate real-time risk assessment in clinical settings.

The cohort included 1413 hospitalized COVID-19 patients. Elderly patients (≥60 years, N = 971) had a high mortality rate of 18.13%. Four independent predictors of mortality were identified: age (HR = 1.07), serum albumin (HR = 0.88), serum potassium (HR = 0.35), and serum sodium (HR = 0.91). The developed risk score demonstrated strong predictive performance and effectively stratified patients into risk categories.

We developed a validated clinical risk score integrating age, serum albumin, potassium, and sodium levels to predict mortality in hospitalized elderly COVID-19 patients. This scoring system enables early risk stratification, assisting clinicians in decision-making and optimizing patient management.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host immune response to pathogenic infection. Due to its high mortality rate, it has been a major global public health problem. Recent studies have shown that the formation of immunothrombosis plays as a "double-edged sword" in the pathogenesis of sepsis, and how to properly regulate immunothrombosis to avoid organ damage and end the high-inflammation state as early as possible are the key steps for sepsis therapy. Considering the complexity of sepsis therapy, the development of an effective combined therapeutic strategy is the goal of this study. First, the insoluble Panexin1 (Panx1) channel inhibitor probenecid (Prob) was prepared as nanocrystals and administered via intramuscular injection. At the same time, septic mice were intravenously injected with cefotaxime sodium through the tail vein for combination therapy. After treatment, the number of infection foci and the level of serum inflammatory factors in septic mice were significantly reduced, and also neutrophil NETosis was significantly inhibited; thus, the survival rate of septic mice was dramatically increased. Pathological analysis revealed that the combination treatment was safe and effective and could significantly reduce the formation of immunothrombosis in septic mice.