Currently, the Omicron variant of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate globally. In our multiplex respiratory pathogen detection, we identified numerous instances of co-infection with Echovirus (ECHO) among Coronavirus Disease 2019 (COVID-19) patients, which exacerbated the clinical symptoms of these patients. Such co-infections are likely to impact the subsequent medical treatment. To date, there are no reports on the pathogenic mechanisms related to COVID-19 co-infected with ECHO. Therefore, this study employed the TM Widely-Targeted metabolomics approach to analyze the serum metabolomes of COVID-19 patients with single SARS-CoV-2 infection (COVID-19), COVID-19 patients co-infected with ECHO (COVID-19  +  ECHO), and healthy individuals (Control) recruited from routine physical examinations during the same period. Concurrent clinical laboratory tests were performed on the patients to reveal the differences in metabolomic characteristics between the COVID-19 patients and the COVID-19  +  ECHO patients, as well as to explore potential metabolic pathways that may exacerbate disease progression. Our findings indicate that both clinical examination indicators and the pathways enriched by differential metabolites confirm that patients with dual infection exhibit higher inflammatory and immune responses compared to those with single COVID-19 infections. This difference is likely reflected through abnormalities in the glycerophospholipid metabolic pathway, with the metabolite Sn-Glycero-3-Phosphocholine playing a crucial role in this process. Finally, we established a diagnostic model based on logistic regression using five differential metabolites, which accurately differentiates between the dual infection population and the single COVID-19 infection population (AUC = 0.828).

Long COVID-19 is marked by persistent symptoms beyond the acute phase, necessitating a deeper understanding of mortality risk factors for effective management. Plasma proteins hold promise as prognostic markers, offering insights into disease progression and aiding in mortality risk assessment.

A total of 240 patients and 89 healthy controls were enrolled for this study. Two months post-COVID follow-up, patients were categorized as survivors (n = 212) and non-survivors (n = 28). Plasma samples underwent 2-dimensional Gel Electrophoresis (2DE) for protein separation, followed by LC-MS/MS for protein identification, and validation was performed using ELISA. Proteomic data analysis was conducted using Mascot version 2.3.02 and Samespots software 4.5.1. Statistical analyses were carried out using GraphPad Prism and IBM SPSS.

LC-MS/MS identified fibrinogen (Spot 14; 52.15 kDa/5.32 pI; protein score 2293) and haptoglobin (Spot 08; 45.86 kDa/6.56 pI; protein score 453) as prospective predictive biomarkers. ELISA results confirmed increased plasma levels of fibrinogen and haptoglobin in severe cases (P < 0.001 for both) and non-survivors (P < 0.01 and P < 0.0086, respectively). ROC analysis showed haptoglobin had moderate predictive power for mortality (AUC = 0.68; P = 0.0025), surpassing fibrinogen (AUC = 0.62; P = 0.0374).

Plasma fibrinogen and haptoglobin are promising biomarkers for assessing disease severity and mortality risk in long COVID. These findings highlight their potential for prognostic applications, warranting further research into their mechanistic roles in COVID-19 and broader clinical implications.

BackgroundCOVID-19 causes a severe respiratory distress syndrome. Systemic inflammation and hypercoagulability are common. These findings are often evaluated with non-specific markers, including CRP, D-dimer, and fibrinogen. We sought to evaluate thromboelastography (TEG) to better understand this complex coagulopathy.MethodsWe conducted a prospective observational study analyzing TEG results in hospitalized patients with COVID-19. TEG was performed on admission and at pre-set intervals. Based on the TEG findings, patients were deemed "hypercoagulable" or "not hypercoagulable." Clinical outcomes were recorded.Results88 patients were evaluated. 78/88 (89%) were hypercoagulable. 10% of the hypercoagulable group (8/78) died compared to none in the non-hypercoagulable group (0/10), with thrombotic events occurring in 9% (8/88), a higher requirement for O2 support in 19% (17/88), and prolonged length of stay exceeding 4 days for 74% (65/88). No statistical significant differences were observed between the groups for any of the four adverse events. Patients with complete fibrinolysis shutdown (Ly30 = 0) had more thrombotic events than those with Ly30 > 0 (30% vs 0%, p = .03).ConclusionPatients with COVID-19 are often hypercoagulable based upon specific TEG parameters. While many TEG parameters are not associated with adverse outcomes, complete fibrinolysis shutdown is associated with an increased risk of thrombotic events. Further studies are warranted to assess the utility of TEG in this population.

Background and Objectives: Coronary artery bypass graft (CABG) surgery is the most common cardiac surgery. One of the main causes of postoperative complications and increased mortality after CABG is the inflammatory response. The aim of this study was to investigate whether continuous intraoperative dexmedetomidine can reduce the increase of IL-6 and other inflammatory markers after CABG surgery. Materials and Methods: The study is registered with ClinicalTrials.gov, NCT06378827, accessed on 23 April 2024. This prospective experimental study was conducted from April to December 2024 and included 100 patients undergoing CABG surgery. Patients in the experimental group (50 patients) received a continuous infusion of dexmedetomidine (0.5 μg/kg/h) from anesthesia induction until the end of surgery, while the patients in the control group (50 patients) received the same volume of saline. The primary outcomes were the changes in the values of interleukin-6 (IL-6), C-reactive protein (CRP), white blood cells (WBC), and fibrinogen on the first postoperative day (POD1) compared to the basal, preoperative values. Results: The patients in the control group were on average 65.26 years old, and the patients in the experimental group were 66.28 years old (p = 0.555). From the control group, 40 (80%) patients were male compared to 37 (74%) patients from the experimental group (p = 0.635). Median IL-6 before surgery was 2.0 pg/mL, while on POD 1 it was 76.2 pg/mL (p < 0.001). Median CRP before surgery was 2.5 mg/dL, while the POD1 value was 45.5 mg/dL (p < 0.001). Median WBC values were 6.7 × 109/L before surgery and 13.6 × 109/L on POD1 (p < 0.001). The average value of fibrinogen was 3.19 g/L before surgery, while on POD1 it was 3.37 g/L (p = 0.024). The increase in IL-6 on POD1 (ΔIL-6) was 72.4 pg/mL in the control group and 73.0 pg/mL in the experimental group (p = 0.427). ΔCRP was 41.2 mg/mL (control group) and 38.0 mg/mL (experimental group) (p = 0.725). ΔWBC was 7.45 × 109/L (control group) and 6.81 × 109/L (experimental group) (p = 0.407). Δfibrinogen was 0.16 g/L (control group) and 0.2 g/L (experimental group) (p = 0.771). Conclusions: Intraoperative administration of dexmedetodine during CABG surgery at a dose of 0.5 µg/kg/h without a loading dose does not lead to a decrease in the intensity of the inflammatory response after surgery.

Background/Objectives: Chronic obstructive pulmonary disease (COPD) patients are at heightened risk of severe COVID-19 due to underlying respiratory impairment, systemic inflammation, and immune dysregulation. This review explores the hematological changes that occur in COPD patients with COVID-19 and their implications for disease progression, prognosis, and clinical management. Methods: We conducted a comprehensive analysis of recent peer-reviewed studies from medical databases including Clarivate Analytics, PubMed, and Google Scholar. Results: Hematological alterations, such as lymphopenia, elevated neutrophil-to-lymphocyte ratio (NLR), increased D-dimer and fibrinogen levels, inflammatory anemia, and erythrocyte dysfunction, are commonly observed in COPD patients with COVID-19. These changes are linked to immune suppression, hyperinflammation, oxidative stress, and thromboembolic complications. Conclusions: Hematological biomarkers are valuable tools for early risk assessments and guiding treatment strategies in this high-risk population. The regular monitoring of D-dimer, fibrinogen, and NLR is advisable. Prophylactic anticoagulation and immunomodulatory therapies, such as corticosteroids and IL-6 and IL-1 inhibitors, may improve clinical outcomes. Further clinical studies are needed to validate personalized approaches and explore antioxidant-based interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underwent significant mutations, resulting in the Omicron variant.

In this study, we analyzed blood samples from 98 patients with acute coronavirus disease 19 (COVID-19) hospitalized during the initial SARS-CoV-2 wave and the onset of Omicron in 2021. High-resolution melting (HRM) analysis of PCR products was used to analyze RNA extracted from clinical samples collected in July and November 2021 from patients infected with SARS-CoV-2.

HRM analysis revealed a characteristic deletion in the N protein RNA of the virus isolated in November 2021, associated with the Omicron variant. Elevated levels of inflammatory markers and interleukin-6 (IL-6) were observed in both waves of COVID-19. Complement levels and IgG and IgM antibodies to SARS-CoV-2 were detected more often during the second wave. An increase in hemagglutinin-inhibiting (HI) antibodies against influenza viruses was observed in paired blood specimens from moderate to severe COVID-19 patients during both outbreaks.

Patients admitted during both waves of COVID-19 showed a significant rise in inflammatory markers, suggesting that Omicron triggers inflammatory responses. The rapid formation of IgM and IgG in Omicron may indicate a faster immune response. Seasonal flu may negatively impact the clinical course of coronavirus infections.

Hemostasis is a mechanism that stops bleeding from an injured vessel, involves multiple interlinked steps, culminating in the formation of a "clot" sealing the damaged area. Moreover, it has long been recognized that inflammation also provokes the activation of the coagulation system. However, there has been an increasing amount of evidence revealing the immune function of the hemostasis system. This review collects and analyzes the results of the experimental studies and data from clinical observations confirming the inflammatory function of hemostasis. Here, we summarize the latest knowledge of the pathways in immune system activation under the influence of coagulation factors. The data analyzed allow us to consider the components of hemostasis as receptors recognizing «foreign» or damaged «self» or/and as «self» damage signals that initiate and reinforce inflammation and affect the direction of the adaptive immune response. To sum up, the findings collected in the review allow us to classify the coagulation factors, such as Damage-Associated Molecular Patterns that break down the conventional concepts of the coagulation system.

It would be highly valuable to possess a tool for evaluating disease progression and identifying patients at risk of experiencing a more severe clinical course and potentially worse outcomes. The concept of allostatic load, which represents the overall strain on the body from repeated stress responses, has been recognized as a precursor to the development of chronic illnesses. It functions as a cumulative measure of the body's capacity to adapt to stress. Numerous studies have demonstrated that elevated allostatic load levels are associated with various negative health outcomes, both physical and mental, and are more predictive of mortality than individual biomarkers. Leveraging the unique circumstances presented by the COVID-19 pandemic, we evaluated different clinical and laboratory parameters in hospitalised COVID-19 patients to assess allostatic load. Our results indicated that allostatic load acts as a strong predictor of prolonged hospitalisation, increased ICU days, and mortality. This highlights its efficacy as a precise gauge of biological dysregulation linked to the response to COVID-19 during disease progression. Allostatic load is easily obtainable and provides an early, cost-effective indication of disease prognosis. Additionally, it has the potential to forecast the necessity for ICU admission. As a result, this parameter, indicative of the comprehensive physiological disruption in response to stress, emerges as a promising prognostic marker for hospitalised patients, extending beyond COVID-19.

SARS-CoV2 infections increase the risk of ischemic stroke (IS), potentially through a thromboinflammatory cascade driven by an imbalance in the ratio of Von Willebrand Factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), leading to the formation of ultra-large VWF (UL-VWF). However, the SARS-CoV2 infection's contribution to any VWF/ADAMTS13 axis imbalance and the subsequent thromboinflammatory response post-stroke remain poorly understood.

We performed a detailed thromboinflammatory profile of the plasma samples from three experimental cohorts matched by age, sex, and stroke severity: non-stroke controls (n = 23), SARS-CoV2 negative IS (n = 22), and SARS-CoV2 positive IS (n = 24). SARS-CoV2 positive IS patients presented varying degrees of infection severity.

We observed an increase in VWF and UL-VWF and a decrease in ADAMTS13 in the SARS-CoV2 positive IS cohort, suggesting a VWF/ADAMTS13 axis imbalance. Interleukin-6 (IL-6) levels were positively correlated with VWF and negatively correlated with ADAMTS13, suggesting that IL-6 may drive this imbalance. Fibrinogen and D-Dimers were elevated in SARS-CoV2 negative IS cohort and SARS-CoV2 positive IS cohort, but D-Dimers were within the normal range, indicating no disseminated intravascular coagulation. Factor IX (FIX) was elevated in the SARS-CoV2 negative IS cohort. Tissue plasminogen activator (tPA) was elevated in the SARS-CoV2 positive IS cohort, suggesting no fibrinolysis defects. Matrix Metalloproteinase-2 (MMP-2) and soluble Intracellular Adhesion Molecule-1 (sICAM-1) were elevated in the SARS-CoV2 negative IS cohort.

We show that SARS-CoV2 infections drive a VWF/ADAMTS13 axis imbalance, inducing an increase in tPA while decreasing FIX, MMP-2, and sICAM-1 post-stroke.

Atrial fibrillation (AF) is the most common heart arrhythmia, linked to a five-fold increase in stroke risk. The left atrial appendage (LAA), prone to blood stasis, is a common thrombus formation site in AF patients. The LAA can be classified into four morphologies: broccoli, cactus, chicken wing and windsock. Stroke risk prediction in AF typically relies on demographic characteristics and comorbidities, often overlooking blood flow dynamics. We developed patient-specific non-Newtonian models of blood flow, dependent on fibrinogen and haematocrit, to predict changes in LAA viscosity, aiming to predict stroke in AF patients. We conducted 480 computational fluid dynamics (CFD) simulations using the non-Newtonian model across the four LAA morphologies for four virtual patient cohorts: AF + Covid-19, AF + pathological fibrinogen, AF + normal fibrinogen, and healthy controls. Gaussian process emulators (GPEs) were trained on this in silico cohort to predict average LAA viscosity at near-zero computational cost. GPEs demonstrated high accuracy in AF cohorts but lower accuracy when the chicken wing GPE was applied to other morphologies. Global sensitivity analysis showed fibrinogen significantly influenced blood viscosity in all AF cohorts. The chicken wing morphology exhibited the highest viscosity, while the AF + Covid-19 cohort had the highest viscosity. Our non-Newtonian model in CFD simulations confirmed fibrinogen's substantial impact on blood viscosity at low shear rates in the LAA, suggesting that combining blood values and geometric parameters of the LAA into GPE training could enhance stroke risk stratification accuracy. KEY POINTS: Fibrinogen has a significant effect on blood viscosity in the left atrial appendage (LAA) at low shear rates. Gaussian process emulators (GPEs) can predict the viscosity of blood in the LAA at near-zero computational cost. Out of all LAA morphologies, the chicken wing morphology exhibited the highest average blood viscosity. High average blood viscosity in the LAA of atrial fibrilation + Covid-19 patients was observed due to high fibrinogen levels in this cohort. Combining blood values and geometric parameters of the LAA into GPE training could enhance stroke risk stratification accuracy.

The aim of the present study was to identify more effective laboratory markers to assess the severity of corona virus disease 2019 and predict the progression of the disease by collecting more laboratory markers and variables.

In this study, most risk factors, including epidemiological characteristics, blood cell counts, cytokines, and infection markers, were collected from 126 patients with COVID-19 to assess their predictive value.

The area under curve (AUC) of Albumin (Alb) to fibrinogen (Fib) ratio (AFR) (0.791), Lactate dehydrogenase (LDH) (0.792), myoglobin (MYO) (0.795), C-reactive protein (CRP) (0.801) and lymphocyte count (0.859) were higher than other markers to distinguish severe from non-severe patients in receiver operating characteristic (ROC) analysis. In the univariate logistic regression analysis, thirty-six out of 46 risk factors, including 34 laboratory markers, were significantly associated with increased odds of severe patients. Multivariate logistic regression analysis showed that the CD19+ lymphocyte count, MYO, LDH, and AFR were associated with increased odds of severe disease. Moreover, Lymphocyte count and AFR levels increased, LDH and CRP levels decreased during hospitalization in recovered severe patients, whereas severe lymphocytopenia and continuously increasing LDH levels were observed in deteriorated patients. AFR level increased and CRP level decreased before the disease worsened in the deteriorated patients; however, when the patients deteriorated, AFR decreased and CRP increased significantly.

CD19+ lymphocyte count, MYO, LDH, and AFR are independent biomarkers for early identification of severe COVID-19. Lymphocyte count, AFR, LDH, and CRP levels were helpful in predicting the clinical progression of the disease.\.

Understanding the pathobiology of critical illness is essential for patients' prognosis. Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As part of the host response, procoagulant responses, one of the most primitive reactions in biology, start at the very beginning of diseases and can be monitored throughout the process. Currently, we can achieve near-complete monitoring of the coagulation process, and procoagulant responses serve as indicators of the severity of host response in critically ill patients. However, the rapid interpretation of the complex results of various biomarkers remains a challenge for many clinicians. The indicators commonly used for coagulation assessment are complex, typically divided into three categories for clarity: process index, functional index, and outcome index. Monitoring and understanding these indicators can help manage procoagulant responses. The intervention of procoagulant response should be part of the bundle therapy, alongside the treatment for primary disease, management for hemodynamics, and controlling for host response. Early intervention for procoagulant response mainly includes anti-inflammation, antiplatelet and anticoagulant therapy, as well as management of primary disease. In this review, we systemically introduce the onset, assessment and intervention of procoagulant response.

The ability of the SARS-CoV-2 virus to cause DNA damage in infected humans requires its study as a potential indicator of COVID-19 progression. DNA damage was studied in leukocytes of 65 COVID-19 patients stratified by sex, age, and disease severity in relation to demographic, clinical, and laboratory parameters. In a combined group of COVID-19 patients, DNA damage was shown to be elevated compared to controls (12.44% vs. 5.09%, p < 0.05). Severe cases showed higher DNA damage than moderate cases (14.66% vs. 10.65%, p < 0.05), and males displayed more damage than females (13.45% vs. 8.15%, p < 0.05). DNA damage is also correlated with international normalized ratio (INR) (r = 0.471, p < 0.001) and creatinine (r = 0.326, p < 0.05). In addition to DNA damage, severe COVID-19 is associated with age, C-reactive protein (CRP), and creatinine. Receiver operating characteristic analysis identified age, INR, creatinine, DNA damage, and CRP as significant predictors of disease severity, with cut-off values of 72.50 years, 1.46 s, 78.0 µmol/L, 9.72%, and 50.0 mg/L, respectively. The results show that DNA damage correlates with commonly accepted COVID-19 risk factors. These findings underscore the potential of DNA damage as a biomarker for COVID-19 severity, suggesting its inclusion in prognostic assessments to facilitate early intervention and improve patient outcomes.

Since the start of the pandemic, considerable advancements have been made in our understanding of the effects of SARS-CoV-2 infection and the associated COVID-19 on the hepatic system. There is a broad range of clinical symptoms for COVID-19. It affects multiple systems and has a dominant lung illness depending on complications. The progression of COVID-19 in people with pre-existing chronic liver disease (CLD) has also been studied in large multinational groups. Notably, SARS-CoV-2 infection is associated with a higher risk of hepatic decompensation and death in patients with cirrhosis. In this review, the source, composition, mechanisms, transmission characteristics, clinical characteristics, therapy, and prevention of SARS-CoV-2 were clarified and discussed, as well as the evolution and variations of the virus. This review briefly discusses the causes and effects of SARS-CoV-2 infection in patients with CLD. As part of COVID-19, In addition, we assess the potential of liver biochemistry as a diagnostic tool examine the data on direct viral infection of liver cells, and investigate potential pathways driving SARS-CoV-2-related liver damage. Finally, we explore how the pandemic has had a significant impact on patient behaviors and hepatology services, which may increase the prevalence and severity of liver disease in the future. The topics encompassed in this review encompass the intricate relationships between SARS-CoV-2, liver health, and broader health management strategies, providing valuable insights for both current clinical practice and future research directions.

Prior research had indicated a relationship between fibrinogen and stroke-associated pneumonia (SAP), yet the nature of this relationship had not been thoroughly investigated. Therefore, this study was designed to elucidate the prognostic value of fibrinogen levels in forecasting the occurrence of SAP among patients with acute ischemic stroke (AIS).

In this retrospective cross-sectional analysis, we included 1092 patients who had experienced AIS and were admitted to our facility within 72 h of the onset of their symptoms. Based on the SAP diagnostic criteria, patients were classified into two groups: SAP and non-SAP. The correlation between serum fibrinogen concentration and SAP was examined using univariate analysis. Curve fitting and multivariable logistic regression model were utilized for statistical evaluation.

Out of the ischemic stroke patients included in the study, SAP was identified in 112 (10.26%) patients. A direct correlation was observed between fibrinogen levels and the incidence of SAP. An increase in fibrinogen levels corresponded with a heightened incidence of SAP. Multivariable logistic regression revealed a significant positive association between fibrinogen levels and SAP incidence (OR = 1.53, 95% confidence interval [CI]: 1.18, 1.99)).

A linear relationship between serum fibrinogen levels and the incidence of SAP in ischemic stroke patients was shown. The serum fibrinogen levels were positively and linearly correlated to SAP risk.

Several studies reported the effect of COVID-19 on inducing gut dysbiosis, which is also correlated with disease severity. This study aims to investigate the effect of a nutraceutical formula on the shift of microbiota profiles and, secondly, on the clinical-pathological parameters of acute and post-acute COVID-19 patients.

In this randomised, double-blind, placebo-controlled trial conducted at National Institute for Infectious diseases (INMI) Lazzaro Spallanzani (Italy), 52 patients were randomly assigned (1:1) to receive a multistrain synbiotic formula (Kebirah®) or placebo orally for 35 days at COVID-19 diagnosis. Health professionals, investigators, and patients were masked to group assignments. The V3-V4 hypervariable region of 16S rRNA gene sequencing was employed to study the gut microbiota composition in the two groups.

Supplementation with Kebirah® prevented the decrease in the Shannon diversity index of gut microbiota, which was instead observed in patients receiving the placebo. In addition, decreases in lymphocyte count and haemoglobin levels were observed only in the placebo group and not in the treated group, which was also characterised by an amelioration of the gut microbial profile, with an enrichment in beneficial bacteria and a preservation of species diversity.

Our data suggest that modulating the gut microbiota in acute disease through administration of a specific symbiotic formula could be a useful strategy in the frame of SARS-CoV-2 infections.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical manifestations with the potential to progress to multiple organ dysfunction in severe cases. Extracellular vesicles (EVs) carry a range of biological cargoes, which may be used as biomarkers of disease state.

An exploratory secondary analysis of the SARITA-2 and SARITA-1 datasets (randomized clinical trials on patients with mild and moderate/severe COVID-19) was performed. Serum-derived EVs were used for proteomic analysis to identify enriched biological processes and key proteins, thus providing insights into differences in disease severity. Serum-derived EVs were separated from patients with COVID-19 by size exclusion chromatography and nanoparticle tracking analysis was used to determine particle concentration and diameter. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to identify and quantify protein signatures. Bioinformatics and multivariate statistical analysis were applied to distinguish candidate proteins associated with disease severity (mild versus moderate/severe COVID-19).

No differences were observed in terms of the concentration and diameter of enriched EVs between mild (n = 14) and moderate/severe (n = 30) COVID-19. A total of 414 proteins were found to be present in EVs, of which 360 were shared while 48 were uniquely present in severe/moderate compared to mild COVID-19. The main biological signatures in moderate/severe COVID-19 were associated with platelet degranulation, exocytosis, complement activation, immune effector activation, and humoral immune response. Von Willebrand factor, serum amyloid A-2 protein, histone H4 and H2A type 2-C, and fibrinogen β-chain were the most differentially expressed proteins between severity groups.

Exploratory proteomic analysis of serum-derived EVs from patients with COVID-19 detected key proteins related to immune response and activation of coagulation and complement pathways, which are associated with disease severity. Our data suggest that EV proteins may be relevant biomarkers of disease state and prognosis.

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a disease newly discovered in December 2019 which affects coagulation cascade and liver functions. The aim of this study was to investigate the potential of hemostatic and liver function parameters as severity markers in COVID-19 patients. This study was an observational analytic with cohort retrospective design using total sampling method. Data were retrieved from medical record of COVID-19 patients admitted to provincial hospital in Banda Aceh, Indonesia from March 2020 to March 2022. There were 1208 data eligible for the study after applying certain criteria. Mann-Whitney, logistic regression, and receiving operating characteristic (ROC) analyses were used to analysis the data. Thrombocyte count (p<0.001), prothrombin time (p<0.001), activated partial thromboplastin time (p<0.001), D-dimer (p<0.001), fibrinogen (p<0.001), aspartate aminotransferase (p<0.001), and alanine transaminase (p<0.001) significantly increased in severe compared to mild COVID-19 patients. After being adjusted, age (odds ratio (OR); 1.026 (95% confidence interval (CI): 1.016-1.037) was the most significant factor in predicting COVID-19 severity. Fibrinogen (cut-off 526.5 mg/L) was the best parameter associated with COVID-19 severity with 70% sensitivity and 66.4% specificity. Meanwhile, D-dimer (cut-off 805 ng/mL) had a sensitivity of 72.3% and specificity of 66.4%. Combining the parameters resulted in improved sensitivity to 82.0% with a slight decline of specificity to 65.5%. In conclusion, fibrinogen and D-dimer level on admission could be used as biomarkers in predicting COVID-19 prognosis. Routine monitoring and evaluation of laboratory testing especially D-dimer and fibrinogen could be implemented in order to reduce morbidity and mortality rate of COVID-19.

Individuals experiencing severe cases of Coronavirus Disease 2019 (COVID-19) exhibited elevated fibrinogen levels and decreased albumin levels, potentially linked to the presence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins. Consequently, our study endeavors to examine the impact of SARS-CoV-2 ORF9b on the expression of fibrinogen and albumin genes within the Hep-G2 cell line.

In this study, the Hep-G2 liver cell line was utilized alongside the plasmid pcDNA3.1 hyg+ containing ORF9b from the SARS-CoV-2 strain originating in Wuhan. Transfection procedures were executed, and the transfected cells were selected utilizing hygromycin B. Validation of ORF9b expression was conducted through SYBR green-based real-time PCR, and the expression of the Fibrinogen α (FGA), Fibrinogen β (FGB), Fibrinogen γ (FGG), and Albumin (ALB) genes was quantified using the same method.

The real-time PCR analysis revealed a significant upregulation of fibrinogen genes-α (P=0.03), β (P=0.02), and γ (P=0.029) in Hep-G2 cells containing ORF9b compared to control cells. Furthermore, the findings indicated a markedly lower expression level of albumin in Hep-G2 cells harboring ORF9b compared to the control cells (P=0.028).

The findings suggest that SARS-CoV-2 ORF9b could potentially influence the course of SARS-CoV-2 infection by triggering the expression of α, β, and γ fibrinogen gene chains while suppressing the albumin gene. Further investigations are warranted to validate these observations across various SARS-CoV-2 strains exhibiting differing levels of pathogenicity.

Candidemia is the most common serious fungal infection in critically ill patients in intensive care units (ICU). It series fourth among bloodstream infectious agents. In this study, candidemia risk analysis was examined in COVID 19 and non-COVID 19 patients during the pandemic period.

COVID 19 and non-COVID 19 cases who were followed up with candidemia in the ICU of our hospital were retrospectively screened. Demographic data, intubation, central venous catheter (CVC), medications, and total parenteral nutrition (TPN) status were evaluated in terms of risk between the two groups. Isolated Candida species and susceptibilty were evaluated.

When age, gender, medication, intubation, TPN and CVC were evaluated, no difference was seen in terms of risk. Differences were detected in terms of comorbidities. While the most frequently identified Candida species was C. albicans, the most frequently detected species in the COVID19 patient group was C. parapsilosis.

There was no difference in candidemia incidence and risk factors between the two groups. Since candidemias were evaluated in terms of comorbidities, it was determined that Diabetes Mellitus (DM) and chronic obstructive pulmoner disease (COPD) were more common in patients with COVID 19 and less common in coronary artery disease (CAD) and malignancy.

Endocan is an endothelial-cell-specific proteoglycan (ESM-1) and has emerged as an endothelial dysfunction and inflammatory marker in recent years. Endocan can be used as a marker of inflammatory endothelial dysfunction in endothelium-dependent disease: cardiovascular disease, sepsis, lung and kidney disease and malignancies. Recent data suggest that endothelial dysfunction is a key mechanism in COVID-19 pathogenesis. Endotheliitis and thrombo-inflammation are associated with severe forms of SARS-CoV-2 infection, and endocan is currently under investigation as a potential diagnostic and prognostic marker. The aim of this study was to determine serum endocan levels in patients with COVID-19 to evaluate the correlation between endocan levels and clinical disease diagnosis and prognosis. This study enrolled 56 patients, divided into three groups depending on disease severity: mild (15), moderate (25) and severe (16). The biochemical, demographic, clinical and imagistic data were collected and evaluated in correlation with the endocan levels. Serum endocan levels were significantly higher in the COVID-19 patients compared to the control group; also, endocan concentration correlated with vaccination status. The results revealed significantly elevated serum endocan levels in COVID-19 patients compared to the control group, with a correlation observed between endocan concentration and vaccination status. These findings suggest that endocan may serve as a novel biomarker for detecting inflammation and endothelial dysfunction risk in COVID-19 patients. There was no significant relationship between serum endocan levels and disease severity or the presence of cardiovascular diseases. Endocan can be considered a novel biomarker for the detection of inflammation and endothelial dysfunction risk in COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019. It presents one of the most threatening pandemics in the history of humanity. The mortality and morbidity represent an unprecedented challenge to the modern medical era. SARS-CoV-2 results in acute respiratory distress syndrome, high concentrations of proinflammatory mediators, cytokine storm (CS) due to massive release of cytokines, hypercoagulation, and hemoglobin disintegration. Dysregulation of iron homeostasis, iron overload as indicated by high ferritin level, and ferroptosis are major factors in the pathogenesis of the disease. We report a case of SARS-CoV-2 in which the use of epinephrine (Epi) resulted in an unexpected attenuation of CS, decreasing ferritin level and inhibiting ferroptosis.

A 64-year-old male patient with a history of multiple medical comorbidities had been diagnosed with SARS-CoV-2. Further evaluation showed marked increase in inflammatory markers, severe hyperferritinemia, and lymphopenia in laboratory blood tests. The characteristic score of CS was strongly positive, and in addition to regular treatment, the patient received Epi due to development of acute generalized skin rash, severe itching, and edema of lips and tongue. Epi may have successfully terminated not only the acute cutaneous condition, but also have attenuated CS, decreased ferritin level, and other inflammatory markers in addition to complete patient's recovery.

Epinephrine may attenuate CS and inhibit ferroptosis which is an iron-dependent, non-apoptotic mode of cell death. Epi interacts with ferric and/or ferrous iron and built a stable complex that impedes activation of beta-adrenergic receptors. Epi may cause marked decrease of ferritin and other inflammatory markers. Epi may be used to decrease iron overload which is associated with many medical diseases like type 2 diabetes mellitus and cardiometabolic diseases such as coronary heart disease and cerebrovascular disease. As a new clinical indication extensive studies are required for further assessment and possible therapeutic uses.

Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae. Besides, it may cause alterations in primary, secondary, and tertiary hemostasis. Importantly, these responses have been highly decisive in the evolution of infected patients also diagnosed with diabetes mellitus (DM), who showed previous endothelial dysfunction. In this review, we provide an overview of the potential triggers of endothelial activation related to COVID-19 and COVID-19 under diabetic milieu. Several mechanisms are induced by both the viral particle itself and by the subsequent immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, activation of the complement system). Alterations in coagulation mediators such as factor VIII, fibrin, tissue factor, the von Willebrand factor: ADAMST-13 ratio, and the kallikrein-kinin or plasminogen-plasmin systems have been reported. Moreover, an imbalance of thrombotic and thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation and hypofibrinolysis. In the context of DM, these mechanisms can be exacerbated leading to higher loss of hemostasis. However, a series of therapeutic strategies targeting the activated endothelium such as specific antibodies or inhibitors against thrombin, key cytokines, factor X, complement system, the kallikrein-kinin system or NETosis, might represent new opportunities to address this hypercoagulable state present in COVID-19 and DM. Antidiabetics may also ameliorate endothelial dysfunction, inflammation, and platelet aggregation. By improving the microvascular pathology in COVID-19 and post-COVID subjects, the associated comorbidities and the risk of mortality could be reduced.

Altered properties of fibrin clots have been associated with bleeding and thrombotic disorders, including hemophilia or trauma and heart attack or stroke. Clotting factors, such as thrombin and tissue factor, or blood plasma proteins, such as fibrinogen, play critical roles in fibrin network polymerization. The concentrations and combinations of these proteins affect the structure and stability of clots, which can lead to downstream complications. The present work includes clots made from plasma and purified fibrinogen and shows how varying fibrinogen and activation factor concentrations affect the fibrin properties under both conditions. We used a combination of scanning electron microscopy, confocal microscopy, and turbidimetry to analyze clot/fiber structure and polymerization. We quantified the structural and polymerization features and found similar trends with increasing/decreasing fibrinogen and thrombin concentrations for both purified fibrinogen and plasma clots. Using our compiled results, we were able to generate multiple linear regressions that predict structural and polymerization features using various fibrinogen and clotting agent concentrations. This study provides an analysis of structural and polymerization features of clots made with purified fibrinogen or plasma at various fibrinogen and clotting agent concentrations. Our results could be utilized to aid in interpreting results, designing future experiments, or developing relevant mathematical models.

This meta-analysis aimed to investigate the correlation between plasma biomarkers, such as albumin and fibrinogen, and their ratio with postoperative delirium (POD) in patients undergoing non-cardiac surgery.

Relevant observational cohort studies were systematically searched in PubMed, EMBASE, CINAHL, and the Cochrane Library databases as of March 2023. This meta-analysis was conducted using RevMan 5.4.1 and Stata 15.0 software. For continuous variables with non-uniform units, the standardized mean difference (SMD) and 95% confidence intervals (CIs) were used; otherwise, the mean difference (MD) and 95% CIs were employed. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of included literature.

Eighteen studies encompassing 7,011 patients were included. The meta-analysis revealed significantly lower albumin levels (sixteen studies, 5,813 patients, SMD = -0.45, 95% CI = -0.64 to -0.26, P < 0.00001, I2 = 80%) and albumin-fibrinogen ratio (AFR) (four studies, 824 patients, MD = -0.62, 95% CI = -0.76 to -0.48, P = 0.56, I2 = 0%) in the delirious group. Conversely, higher fibrinogen concentrations (two studies, 441 patients, MD = 0.13, 95% CI = 0.02 to 0.24, P = 0.69, I2 = 0%) were observed in the delirious group. Due to high heterogeneity in albumin levels (P < 0.00001, I2 = 80%), we conducted a subgroup and sensitivity analysis, and confirmed that the association of albumin levels was not influenced by surgery type, design or delirium evaluation instruments.

Preoperative albumin, fibrinogen and AFR levels were associated with POD, potentially aiding in identifying high-risk patients and playing a key role in preventing POD.

Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient's baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8-20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination.

The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed.

From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection (n = 2200), while the remaining four studies failed to demonstrate any significant association (n = 38).

This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.

Hospitalized COVID-19 patients exhibit diverse clinical outcomes, with some individuals diverging over time even though their initial disease severity appears similar. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity. In this study, we carried out deep immunophenotyping and conducted longitudinal multi-omics modeling integrating ten distinct assays on a total of 1,152 IMPACC participants and identified several immune cascades that were significant drivers of differential clinical outcomes. Increasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, NETosis, and T-cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma immunoglobulins and B cells, as well as dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to the failure of viral clearance in patients with fatal illness. Our longitudinal multi-omics profiling study revealed novel temporal coordination across diverse omics that potentially explain disease progression, providing insights that inform the targeted development of therapies for hospitalized COVID-19 patients, especially those critically ill.

Oxidative stress plays an important role in the occurrence and development of malignancy. However, the relationship between oxidative stress and upper urinary tract urothelial carcinoma (UTUC) prognosis remains elusive. This study aimed to evaluate the prognostic value of systematic oxidative stress indices as a predictor of patient outcomes in UTUC after radical nephroureterectomy.

Clinical data for 483 patients with UTUC who underwent radical nephroureterectomy were analyzed. Patients were categorized according to an optimal value of systematic oxidative stress indices (SOSIs), including fibrinogen (Fib), gamma-glutamyl transpeptidase (γ-GGT), creatinine (CRE), lactate dehydrogenase (LDH) and albumin (ALB). Kaplan-Meier analyses were used to investigate associations of SOSIs with overall survival (OS) and progression-free survival (PFS). Moreover, associations between SOSIs and OS and PFS were assessed with univariate and multivariate analyses.

High values of Fib, γ-GGT, CRE, and LDH, and low values of ALB were associated with reduced OS. SOSIs status correlated with age, tumor site, surgical approach, hydronephrosis, tumor size, T stage, and lymph node status. The Kaplan-Meier survival analysis showed a significant discriminatory ability for death and progression risks in the two groups based on SOSIs. Multivariate Cox proportional hazards models showed that SOSIs were an independent prognostic indicator for OS (p = 0.007) and PFS (p = 0.021). SOSIs and clinical variables were selected to establish a nomogram for OS. The 1-, 3-, and 5-year AUC values were 0.77, 0.78, and 0.81, respectively. Calibration curves of the nomogram showed high consistencies between the predicted and observed survival probability. Decision curve analysis curves showed that the nomogram could well predict the 1-year, 3-year, and 5-year OS.

SOSIs are an independent unfavorable predictor of OS and PFS in patients diagnosed with UTUC undergoing RNU. Therefore, incorporating SOSIs into currently available clinical parameters may improve clinical decision-making.

The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae of COVID-19 (PASC), sometimes referred to as long COVID. The mechanisms of the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, and several studies have pointed to the central nervous and vascular systems as being potential sites of dysfunction. In the current study, we recruited individuals with PASC with diverse symptoms, and examined the relationship between neuroinflammation and circulating markers of vascular dysfunction. We used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 PASC individuals versus 43 normative healthy controls. We found significantly increased neuroinflammation in PASC versus controls across a wide swath of brain regions including midcingulate and anterior cingulate cortex, corpus callosum, thalamus, basal ganglia, and at the boundaries of ventricles. We also collected and analyzed peripheral blood plasma from the PASC individuals and found significant positive correlations between neuroinflammation and several circulating analytes related to vascular dysfunction. These results suggest that an interaction between neuroinflammation and vascular health may contribute to common symptoms of PASC.

We aimed to investigate the risk factors associated with revitrectomy in eyes with diabetic vitreous hemorrhage and to determine the prognosis of these patients at least one year postoperatively.

This retrospective case-control study had a minimum follow-up period of one year. Patients were divided into single vitrectomy group (control group, n=202) and revitrectomy group (case group, n=36) for analysis. The indications, number, and timing of revitrectomies were documented. And the revitrectomy group was further divided into two vitrectomies group (n=30) and three or more vitrectomies group (n=6). The best-corrected visual acuity (BCVA) at the last follow-up and the occurrence of neovascular glaucoma (NVG) were compared among the single vitrectomy, two vitrectomies and three or more vitrectomies groups. We conducted a thorough collection of patient data and used univariate and binary logistic regression analyses to identify the risk factors associated with revitrectomy.

A total of 197 patients (238 eyes) were included. Thirty-six eyes (15.1%) required revitrectomy with six eyes (2.5%) undergoing three or more vitrectomies during the follow-up period. The median duration of the second vitrectomy was 3 (2-6) months. The indications for a second vitrectomy included 28 eyes (77.8%) of postoperative vitreous hemorrhage and 7 eyes (22.2%) combined with tractional retinal detachment. Patients undergoing three or more vitrectomies had significantly worse postoperative BCVA and a higher incidence of NVG (P<0.01). Fibrinogen> 4 g/L (P<0.001) and preoperative anti-vascular endothelial growth factor intravitreal injection (P=0.015) were independent risk factors for revitrectomy, and glycated hemoglobin A1c (HbA1c)>10% (P=0.049) showed significant difference only in univariate analysis.

Patients requiring revitrectomy tended to have higher fibrinogen levels, tightly adhered fibrovascular membranes, higher HbA1c levels, and worse prognoses.

The unpredictable course of Coronavirus Disease 19 (COVID-19) is making good severity assessment tools crucial. This study aimed to assess the usefulness of serum amyloid A (SAA) and other acute-phase reactants (APRs) in ambulatory care COVID-19 patients and identified relationships between these markers and disease outcomes.

From August to November 2020, patients seen in the outpatient department of the Clinic for Infectious and Tropical Diseases (Belgrade, Serbia) with confirmed COVID-19 were included. Patients were classified into mild, moderate, and severe disease groups based on World Health Organization criteria. SAA, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), ferritin, fibrinogen, D-dimer, albumin, and transferrin were measured. The median values of all APRs were compared between COVID-19 severity groups, hospitalized and non-hospitalized patients, and survivors and non-survivors. The Receiver operator characteristic (ROC) curve analysis was used for the classification characteristics assessment of individual APRs for the severity of illness, hospitalization, and survival.

In order to study effects of macrophage-derived inflammatory mediators associated with systemic inflammation on brain endothelial cells, we have established a co-culture system consisting of bEnd.3 cells and LPS-activated Raw 264.7 cells and performed its cytokine profiling. The cytokine profile of the co-culture model was compared to that of mice treated with intraperitoneal LPS injection. We found that, among cytokines profiled, eight cytokines/chemokines were similarly upregulated in both in vivo mouse and in vitro co-culture model. In contrast to the co-culture model, the cytokine profile of a common mono-culture system consisting of only LPS-activated bEnd.3 cells had little similarity to that of the in vivo mouse model. These results indicate that the co-culture of bEnd.3 cells with LPS-activated Raw 264.7 cells is a better model than the common mono-culture of LPS-activated bEnd.3 cells to investigate the molecular mechanism in endothelial cells, by which systemic inflammation induces neuroinflammation. Moreover, fibrinogen adherence both to bEnd.3 cells in the co-culture and to brain blood vessels in a LPS-treated animal model of Alzheimer's disease increased. To the best of our knowledge, this is the first to utilize bEnd.3 cells co-cultured with LPS-activated Raw 264.7 cells as an in vitro model to investigate the consequence of macrophage-derived inflammatory mediators on brain endothelial cells.

COVID-19 has resulted in an exponential increase in patients with severe respiratory failure requiring extracorporeal membrane oxygenation (ECMO). Patients on ECMO regularly require high volumes of blood and blood products but, so far, there has been no comparison of transfusion requirements between COVID-19 and non-COVID-19. Using electronic patient records at two major UK ECMO centres, Royal Papworth Hospital and University Hospital South Manchester, we reviewed the transfusion requirements of patients requiring ECMO between January 2019 to December 2021. A total of 271 patients, including 168 COVID-19 patients were available for analysis. Since COVID-19 patients spent almost twice as long on ECMO (27.1 vs. 14.16 days, p ≤ 0.0001) we indexed transfusion in both groups to days on ECMO to allow comparison. COVID-19 patients required less red blood cells (RBC) per day (0.408 vs. 0.996, p = 0.0005) but more cryoprecipitate transfusions (0.117 vs. 0.106, p = 0.022) compared to non-COVID-19 patients. COVID-19 patients had more than double the mortality of non-COVID-19 patients (47% vs. 20.4%, p = 0.0001) and those who died during the study period had higher platelet transfusion requirements (p = 0.007) than their non-COVID-19 counterparts. Transfusion requirements and coagulopathy differ between COVID-19 and non-COVID-19 patients. The distinctly different transfusion patterns between the two groups remain difficult to interpret, but further investigations may help explain the haematological aspects of severe COVID-19 infection.

Type 2 diabetic retinopathy is a long-term chronic inflammatory disease. The aim of this study was to investigate the relationship between fibrinogen to albumin ratio (FAR) and retinopathy in type 2 diabetic patients.

This was a retrospective study that included 500 patients with type 2 diabetes mellitus (T2DM), and were divided into non-diabetic retinopathy group (NDR, n=297) and diabetic retinopathy group (DR, n=203) according to fundus examination findings, and the DR group was further divided into non-proliferative retinopathy group (NPDR, n=182) and proliferative retinopathy group (PDR, n=21). Baseline data of patients were collected, and the fibrinogen to albumin ratio (FAR) and neutrophil to lymphocyte ratio (NLR) were calculated to analyze the correlation between FAR and NLR and type 2 diabetic retinopathy.

The FAR and NLR were significantly higher in the DR group compared with the NDR group (both P < 0.001). Spearman correlation analysis showed that FAR was positively correlated with NLR and DR (P < 0.05). As the FAR quartile increased, the prevalence of DR increased (14.8%, 16.7%, 25.1%, and 43.30%, respectively; P < 0.05). Multifactorial logistic regression analysis showed that FAR, diabetic course, systolic blood pressure (SBP) and diabetic peripheral neuropathy (DPN) were risk factors for the development of DR in patients with T2DM. The area under the ROC curve for FAR to predict DR progression was 0.708, with an optimal critical value of 7.04, and the area under the ROC curve for diabetes duration and SBP to predict DR was 0.705 and 0.588, respectively.

Our findings show for the first time that FAR is an independent risk factor for assessing DR in patients with type 2 diabetes.