The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.

The swift transmission rate and unfavorable prognosis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have prompted the pursuit of more effective therapeutic interventions. Azithromycin (AZM) has garnered significant attention for its distinctive pharmacological mechanisms in the treatment of SARS-CoV-2. This study aims to elucidate the biological rationale for employing AZM in patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) who are infected with SARS-CoV-2. Genetic data about COVID-19, COPD, and IPF were independently obtained from the GeneCards database. And 40 drug targets about AZM were retrieved from the STITCH database. The analysis revealed that 311 DEGs were common among COPD, IPF, and COVID-19, and we further found eight genes that interacted with AZM targets. We conducted an analysis of hub genes and their corresponding signaling pathways in these patient cohorts. Additionally, we explored the inhibitory effects of AZM on these hub genes. AZM demonstrated a significant inhibitory effect on eight key genes, except for AR and IL-17 A. These findings suggest that AZM may serve as a promising therapeutic agent for patients with COPD and IPF and SARS-CoV-2 infection.

Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating the effects of these factors. Recent evidence shows patient-specific alterations of RAS peptide homeostasis concentrations with premorbidity and the expression level of angiotensin-converting enzyme 2 (ACE2) during COVID-19. However, conflicting evidence suggests decreases, increases, or no changes in RAS peptides after SARS-CoV-2 infection. A multiscale computational model was developed to quantify the systemic contribution of heterogeneous factors of RAS during COVID-19. Three submodels were connected-an agent-based model for in-host COVID-19 response in the lung tissue, a RAS dynamics model, and a fibrosis dynamics model to investigate the effects of patient-group-specific factors in the systemic alteration of RAS and collagen deposition in the lung. The model results indicated cell death due to inflammatory response as a major contributor to the reduction of ACE and ACE2. The model explained possible mechanisms for conflicting evidence of patient-group-specific changes in RAS peptides in previously published studies. RAS peptides decreased for all virtual patient groups with aging in both sexes. In contrast, large variations in the magnitude of reduction were observed between male and female virtual patients in the older and middle-aged groups. The patient-specific variations in homeostasis RAS peptide concentrations of SARS-CoV-2-negative patients affected the dynamics of RAS during infection. This model may find further applications in patient-specific calibrations of tissue models for acute and chronic lung diseases to develop personalized treatments.

Coronavirus disease 2019 (COVID-19) remains a health problem worldwide. The present study aimed to investigate the effect of blood pressure (BP) on the circadian pattern and prevalence of new-onset non-dipper hypertension in the post-COVID period in patients with known hypertension. This prospective single-center study included 722 patients hospitalized for COVID-19 infection. Ambulatory BP (ABP) data were collected during their initial hospitalization. The ABP data were reassessed 1 month after the patients were discharged. The results were compared with a healthy control group with known hypertension but without COVID-19 infection. After exclusion criteria were applied, the study included 187 patients with COVID-19 and 136 healthy hypertensive controls. Post-COVID ABP showed that patients with COVID-19 had significantly higher mean 24-h systolic and diastolic BP, mean nighttime systolic and diastolic BP, and mean daytime diastolic BP than the control group. In addition, new-onset non-dipper hypertension was significantly higher in patients with COVID-19. This study demonstrated for the first time that the circadian pattern is disturbed and a non-dipper pattern develops in individuals with known hypertension during the post-COVID period.

The intersection of COVID-19 and cardiovascular disease (CVD) has emerged as a significant area of research, particularly in understanding the impact of antiplatelet therapies like ticagrelor and clopidogrel. COVID-19 has been associated with acute cardiovascular complications, including myocardial infarction, thrombosis, and heart failure, exacerbated by the virus's ability to trigger widespread inflammation and endothelial dysfunction. MicroRNAs (miRNAs) play a critical role in regulating these processes by modulating the gene expressions involved in platelet function, inflammation, and vascular homeostasis. This study explores the potential of miRNAs such as miR-223 and miR-126 as biomarkers for predicting resistance or responsiveness to antiplatelet therapies in COVID-19 patients with cardiovascular disease. Identifying miRNA signatures linked to drug efficacy could optimize treatment strategies for patients at high risk of thrombotic events during COVID-19 infection. Moreover, understanding miRNA-mediated pathways offers new insights into how SARS-CoV-2 exacerbates CVD, particularly through mechanisms like cytokine storms and endothelial damage. The findings of this research could lead to personalized therapeutic approaches, improving patient outcomes and reducing mortality in COVID-19-associated cardiovascular events. With global implications, this study addresses the urgent need for effective management of CVD in the context of COVID-19, focusing on the integration of molecular biomarkers to enhance the precision of antiplatelet therapy.

Acute respiratory distress syndrome (ARDS) associated with coronavirus infectious disease (COVID)-19 has been a challenge in intensive care medicine for the past three years. Dysregulation of the renin-angiotensin system (RAS) is linked to COVID-19, but also to non-COVID-19 ARDS. It is still unclear whether changes in the RAS are associated with prognosis of severe COVID-19.

In this prospective exploratory study, blood samples of 94 patients with COVID-19 were taken within 48 h of admission to a medical ward or an ICU. In ICU patients, another blood sample was taken seven days later. Angiotensin (Ang) I-IV, Ang 1-7, Ang 1-5 and aldosterone concentrations were measured with liquid chromatography tandem mass spectrometry (LC-MS/MS) followed by calculation of markers for activities of renin (PRA-S) and ACE (ACE-S), alternative RAS activation (ALT-S) as well as the ratio of aldosterone to Ang II (AA2R). Angiotensin-converting enzyme (ACE) and ACE2 concentrations were measured by LC-MS/MS-based assays. All RAS parameters were evaluated as predictors of 28-day and 60-day survival using receiver operating characteristic and multivariate logistic regression analysis.

AA2R at inclusion was a predictor of 60-day survival for ICU patients with an AUROC of 0.73. Ang II and active ACE2 were inversely associated with survival (OR 0.07; 95%CI 0.01, 0.39 and OR 0.10; 95%CI 0.01, 0.63) while higher Ang 1-7 predicted favorable outcome (OR 6.8; 95%CI 1.5, 39.9). ICU patients showed higher concentrations of all measured angiotensin metabolites, PRA-S, ALT-S and active ACE2, and lower ACE-S and AA2R than patients in the medical ward at inclusion. After seven days in the ICU, Ang I, Ang II, Ang III and Ang IV concentrations decreased, while ACE and ACE2 levels increased. Ang I, PRA-S, Ang 1-7 and Ang 1-5 concentrations correlated with the SOFA score both at the time of inclusion and after seven days, and driving pressure after seven days.

AA2R at inclusion predicted 60-day survival with moderate sensitivity, revealing a dissociation between unchanged aldosterone and increased Ang II levels in the most severely ill COVID-19 patients. After adjustment for confounders, Ang 1-7 as the final metabolite of alternative RAS was predictive for survival.

Some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. This review provides an overview of the current literature on the pathophysiological pathways linking coronavirus disease 2019 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, enhanced external counter-pulsation (EECP), is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, involving sequenced inflation and deflation of specifically-placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially via counteracting against the negative effects of SARS-CoV-2 infection on the renin-angiotensin-aldosterone system. Therefore, EECP could promote both psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine its benefits and mechanism of action.

COVID-19, caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), is primarily a respiratory illness but significantly affects the cardiovascular system as well. After entering the body through the respiratory tract, the virus directly and indirectly disrupts the vascular system. Vascular endothelial cells (ECs), which express ACE2 and TMPRSS2, are targets for viral invasion. However, the predominant cause of widespread vascular damage is the "cytokine storm" induced by the immune response. This leads to EC activation, inflammation, neutrophil activation, and neutrophil-platelet aggregation, causing endothelial injury. Additionally, increased expression of plasminogen activator inhibitor-1 disrupts the balance between prothrombotic and fibrinolytic processes, while activation of the renin-angiotensin-aldosterone system adds oxidative stress to the vascular endothelium. In the heart, SARS-CoV-2 invades ECs, leading to apoptosis and pyroptosis, exacerbated by inflammation and elevated catecholamines. These factors contribute to arrhythmias, strokes, and myocardial infarction in severe cases of COVID-19. This narrative review aims to explore the mechanisms by which SARS-CoV-2 affects the cardiovascular system and to highlight the resulting complications. It also identifies research gaps and discusses potential therapeutic strategies to mitigate the cardiovascular impacts of COVID-19.

The COVID-19 disease caused by SARS-CoV-2 was declared as pandemic by WHO soon after its emergence in 2019. This virus was known to cause serious clinical symptoms and severe illness. By using RT-PCR, which reports the cycle threshold value, the disease is diagnosed, whereas for the severity of the disease, biomarker levels, like IL-6, CRP, D-dimer, serum ferritin and serum procalcitonin, can be measured. We, thus, aimed to explore any potential correlation of the cycle threshold value and biomarker level with the outcome of COVID-19-positive hospitalized patients.

Patients with the cycle threshold (Ct) value <35 were included in the study and their initial Ct values were noted. Different biochemical parameters, such as C-reactive protein (CRP), serum ferritin, D-dimer, Interleukin-6 and serum procalcitonin, were assessed for severity. They were classified according to Ct value into three groups: Group 1 >30.0, Group 2 20.0-30.0 and Group 3 <20.0.

The study included 370 hospitalized COVID-19 patients with a mean age (mean ± SD) of 51.08 (16.58%) years and 250 (67.5%) males and 120 (32.4%) females. Comparison of data with outcome shows that IL-6, CRP amongst the biomarker and Ct value (deduced by RT-PCR test) were significantly correlated with the mortality (P value < 0.05). The ROC curve was also plotted for these parameters, which shows that IL-6, CRP, PCT and Ct value were better prognostic marker. Poor prognosis was found in Group 2 (Ct value 20.0-30.0) patients compared to Group 1 and Group 3. There was significant correlation (P value < 0.05) between Ct value and outcome of the patient.

This study depicts that low Ct value and elevated levels of IL-6 and CRP can be used as a screening tool to detect the mortality in COVID-19 patients as they are significantly correlated with the mortality.

Research on SARS-CoV-2, the viral pathogen that causes COVID-19, has identified angiotensin converting enzyme 2 (ACE2) as the primary viral receptor. Several genes that encode viral cofactors, such as TMPRSS2, NRP1, CTSL, and possibly KIM1, have since been discovered. Glutamyl aminopeptidase (APA), encoded by the gene ENPEP, is another cofactor candidate due to similarities in its biological role and high correlation with ACE2 and other human coronavirus receptors, such as aminopeptidase N (APN) and dipeptidyl peptidase 4 (DPP4). Recent studies have proposed a role for ENPEP as a viral receptor in humans, and ENPEP and ACE2 are both closely involved in the renin-angiotensin-aldosterone system proposed to play an important role in SARS-CoV-2 pathophysiology. We performed bioinformatic analyses using publicly available bulk (>17,000 samples from 49 distinct tissues) and single-cell (>2.5 million cells) RNA-Seq gene expression datasets to evaluate the expression and function of the ENPEP gene. We also investigated age- and sex-related changes in ENPEP expression. Overall, expression of ENPEP was highest in the small intestine enterocyte brush border and the kidney cortex. ENPEP is widely expressed in a subset of vascular smooth muscle cells (likely pericytes) in systemic vasculature, the heart, and the brain. ENPEP is expressed at low levels in the lower respiratory epithelium. In the lung, ENPEP is most highly expressed in para-alveolar fibroblasts. Single-cell data revealed ENPEP expression in a substantial fraction of ependymal cells, a finding not reported before in humans. Age increases ENPEP expression in skeletal muscle and the prostate, while decreasing it in the heart and aorta. Angiogenesis was found to be a central biological function associated with the ENPEP gene. Tissue-specific roles, such as protein digestion and fat metabolism, were also identified in the intestine. In the liver, the gene is linked to the complement system, a connection that has not yet been thoroughly investigated. Expression of ENPEP and ACE2 is strongly correlated in the small intestine and renal cortex. Both overall and in blood vessels, ENPEP and ACE2 have a stronger correlation than many other genes associated with SARS-CoV-2, such as TMPRSS2, CTSL, and NRP1. Possible interaction between glutamyl aminopeptidase and SARS-CoV-2 should be investigated experimentally.

SARS-CoV-2 infection is associated with increased cardiovascular (CV) morbidity and mortality, manifesting as increased adverse outcomes in the first 30 days, extending to 12 months. This study aimed to investigate trends in sudden unexpected deaths between 2018 and 2022, with a focus on CV deaths.

A retrospective analysis was performed on autopsy reports (n=9,330) obtained from New South Wales Coroners Court, Australia, specifically targeting cases of unexplained deaths that occurred between 2018 and 2022. Statistical analysis was conducted using chi-square tests and a post hoc analysis with Bonferroni correction, as well as analysis of variance with multiple comparisons.

There were 349 (18.3%) CV deaths in 2018, 346 (18.0%) in 2019, 338 (17.5%) in 2020, 395 (21.9%) in 2021, and (23.4%) 413 in 2022 (p=0.0002). Among CV deaths, the number of deaths from sudden arrhythmic death syndrome were 25 (7.2%) in 2018, 26 (7.5%) in 2019, 18 (5.3%) in 2020, 52 (13.2%) in 2021, and 80 (19.4%) in 2022 (p=0.0001). Atherosclerosis was the most common cause of death among all CV categories; there were 196 (56.2%) atherosclerosis deaths in 2018, 207 (59.8%) in 2019, 192 (56.8%) in 2020, 221 (56.0%) in 2021, and 197 (47.7%) in 2022 (p=0.43). The average age of death from sudden arrhythmic death syndrome (42.8±19.1 years) across 2018-2022 was younger than atherosclerosis (56.2±12.4 years) and total groups (53.1±15.1 years) (p<0.001). Males comprised 76% of all CV deaths from 2018 to 2022 (p<0.0001).

Compared with pre-pandemic data, a noteworthy increase in CV deaths was observed in occurrence with the escalation in COVID-19 cases in Australia. This may be attributed to direct or indirect factors, such as lifestyle modifications, disrupted access to routine cardiac care, or COVID-19 infection-triggered CV deaths.

Angiotensin-converting enzyme 2 (ACE2) receptors facilitate the entry of the causative virus severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) into target cells. Some ACE gene variants have been suggested to be involved in COVID-19 pathogenesis. So, the aim was to assess the association between ACE1 rs4646994 and ACE2 rs2285666 genes polymorphisms and the susceptibility and severity of COVID-19. This case-control study was conducted on 197 patients with COVID-19 and 197 healthy controls. ACE-1 insertion/deletion (I/D) (rs4646994) and ACE2 rs2285666 genes polymorphisms were determined by the amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) technique. The DD genotype of ACE1 I/D polymorphism was associated with increased susceptibility to COVID-19 infection (p = 0.012), whereas the ID genotype of this polymorphism was associated with decreased susceptibility (p = 0.003) (significance level = 0.017). There was no significant association in allele and genotype distribution of ACE2 rs2285666 polymorphism between cases and controls. The ACE1 I/D polymorphism may be considered as a risk factor for COVID-19 susceptibility.

Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and in vitro systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.

Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating the effects of these factors. Recent evidence shows patient-specific alterations of RAS homeostasis concentrations with premorbidity and the expression level of angiotensin-converting enzyme 2 (ACE2) during COVID-19. However, conflicting evidence suggests decreases, increases, or no changes in RAS peptides after SARS-CoV-2 infection. In addition, detailed mechanisms connecting the patient-specific conditions before infection to infection-induced RAS alterations are still unknown. Here, a multiscale computational model was developed to quantify the systemic contribution of heterogeneous factors of RAS during COVID-19. Three submodels were connected-an agent-based model for in-host COVID-19 response in the lung tissue, a RAS dynamics model, and a fibrosis dynamics model to investigate the effects of patient-group-specific factors in the systemic alteration of RAS and collagen deposition in the lung. The model results indicated cell death due to inflammatory response as a major contributor to the reduction of ACE and ACE2. In contrast, there were no significant changes in ACE2 dynamics due to viral-bound internalization of ACE2. The model explained possible mechanisms for conflicting evidence of patient-group-specific changes in RAS peptides in previously published studies. Simulated results were consistent with reported RAS peptide values for SARS-CoV-2-negative and SARS-CoV-2-positive patients. RAS peptides decreased for all virtual patient groups with aging in both sexes. In contrast, large variations in the magnitude of reduction were observed between male and female virtual patients in the older and middle-aged groups. The patient-specific variations in homeostasis RAS peptide concentrations of SARS-CoV-2-negative patients also affected the dynamics of RAS during infection. The model results also showed that feedback between RAS signaling and renin dynamics could restore ANGI homeostasis concentration but failed to restore homeostasis values of RAS peptides downstream of ANGI. In addition, the results showed that ACE2 variations with age and sex significantly altered the concentrations of RAS peptides and led to collagen deposition with slight variations depending on age and sex. This model may find further applications in patient-specific calibrations of tissue models for acute and chronic lung diseases to develop personalized treatments.

The coronavirus disease 2019 (COVID-19) has exhibited escalating contagion and resistance to immunity, resulting in a surge in infections and severe cases. This study endeavors to formulate two nomogram predictive models aimed at discerning patients at heightened risk of severe and fatal outcomes upon hospital admission. The primary objective is to enhance clinical management protocols and mitigate the incidence of severe illness and mortality associated with COVID-19.

1600 patients diagnosed with COVID-19 and discharged from Fujian Provincial Hospital were chosen as the subjects of this study. These patients were categorized into three groups: mild group (n = 940), severe group (n = 433), and fatal group (n = 227). The patients were randomly divided into training and validation cohorts in a 7:3 ratio. COVID-19 symptoms were treated as dependent variables, and univariate regression analysis was conducted for the laboratory indicators. Risk factors with p-values greater than 0.05 in the univariate regression analysis were eliminated. The remaining risk factors were then analyzed using direct multiple regression analysis to establish an unadjusted model. Subsequently, risk factors with p-values greater than 0.05 were further removed. Clinical characteristics were added to the model as adjustment factors, and the method of multiple stepwise regression analysis was employed to derive the final fully adjusted model. The severe and fatal COVID-19 models were converted into nomograms, respectively. Receiver operating characteristic (ROC) curves were utilized to evaluate the discrimination of the nomogram models. Calibration was assessed using the Hosmer-Lemeshow test and calibration curves. Clinical benefit was evaluated by decision curve analysis.

Compared to the mild group, individuals in the severe COVID-19 group exhibited significant increases in age, neutrophil (NEU), and lactate dehydrogenase (LDH) levels, alongside notable decreases in lymphocyte (LYM) and albumin (ALB) levels. Nomogram model incorporating age, NEU, LDH, LYM, and ALB demonstrated efficacy in predicting the onset of severe COVID-19 (AUC = 0.771). Furthermore, history of cerebral infarction and cancer, LDH and ALB as risk factors for fatal COVID-19 cases compared to the severe group. The nomogram model comprising these factors was capable of early identification of COVID-19 fatalities (AUC = 0.748).

Elevated age, NEU, and LDH levels, along with decreased LYM and albumin (ALB) levels, are risk factors for severe illness in hospitalized patients with COVID-19. A history of cerebral infarction and tumors, along with elevated LDH and decreased ALB levels, are risk factors for death in critically ill patients. The nomogram model based on these factors can effectively predict the risk of severe or fatal illness from COVID-19, thereby assisting clinicians in timely interventions to reduce the rates of severe illness and mortality among hospitalized patients. However, the model faces challenges in processing longitudinal data and specific points in time, indicating that there is room for improvement.

The presence of chronic obstructive pulmonary disease (COPD) and COVID-19 infection is a detrimental combination for patients and can cause negative clinical consequences. The investigation aimed to compare sociodemographic and clinical parameters of COPD individuals hospitalized for exacerbations before and at the end of the COVID-19 pandemic. An observational cross-sectional study including 222 patients with COPD was conducted in two stages: a survey and assessment of clinical and laboratory data of patients hospitalized from September 2022 to March 2023 (n=98) and processing of the medical histories of patients with COPD who received hospital treatment in 2017 and 2018 (n=124). A comparative analysis of patients who received inpatient treatment for COPD showed that the frequency of patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) I was half as high after the COVID-19 pandemic, whereas the individuals with GOLD IV were more frequent during the same period (p<0.05). Multiple regression analysis proved the effects of smoking status and previous COVID-19 infection on the health status of patients with COPD according to COPD Assessment Test data (p<0.05). There was an increase in the frequency of comorbid pathologies in the post-COVID period: hypertension, coronary heart disease, gastrointestinal diseases, anemia (p<0.05), and other diseases. This study highlights the significant influence of the COVID-19 infection on people with COPD, which manifested as impaired lung function and an increased incidence of comorbidities.

Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice.

C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.

Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.

Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

The 2019 widespread contagion of the human coronavirus novel type (SARS-CoV-2) led to a pandemic declaration by the World Health Organization. A daily increase in patient numbers has formed an urgent necessity to find suitable targets and treatment options for the novel coronavirus (COVID-19). Despite scientists' struggles to discover quick treatment solutions, few effective specific drugs are approved to control SARS-CoV-2 infections thoroughly. Drug repositioning or Drug repurposing and target-based approaches are promising strategies for facilitating the drug discovery process. Here, we review current in silico, in vitro, in vivo, and clinical updates regarding proposed drugs for prospective treatment options for COVID-19. Drug targets that can direct pharmaceutical sciences efforts to discover new drugs against SARS-CoV-2 are divided into two categories: Virus-based targets, for example, Spike glycoprotein and Nucleocapsid Protein, and host-based targets, for instance, inflammatory cytokines and cell receptors through which the virus infects the cell. A broad spectrum of drugs has been found to show anti-SARS-CoV-2 potential, including antiviral drugs and monoclonal antibodies, statins, anti-inflammatory agents, and herbal products.

Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non-COVID-19 intensive care unit (ICU)-matched controls. A validation cohort included healthy, comorbidity-free patients. The primary outcome compared tissue oxygen resaturation slope (rStO 2 ) in COVID-19 patients and non-COVID ICU controls. rStO 2 was measured post a 3-min vaso-occlusive test during post-occlusive reactive hyperemia (PORH). Additionally, microvascular reactivity was assessed using perfusion index (PI) during PORH and laser speckle contrast imaging post iontophoresis with acetylcholine (ACH), sodium nitroprusside (SNP), and sublingual microcirculation. Results: Overall, 75 patients (25 per cohort) were included. COVID-19 patients exhibited greater severity than ICU controls, as indicated by their SOFA scores (4.0 [3.0; 4.0] vs. 1.0 [0; 1.0], P < 0.001) and PaO 2 /FiO 2 ratios (113 [82; 150] vs. 443 [348; 533], P < 0.001). No significant difference was observed in rStO 2 between the groups. COVID-19 patients showed longer time in reaching peak PI ( P = 0.025), reduced vasodilation with ACH and SNP ( P = 0.010 and P = 0.018, respectively), and increased microvascular density ( P = 0.019) compared to non-COVID-19 ICU controls. Conclusion: We observed evidence of MD in COVID-19 patients through various microcirculatory parameters. This study's reproducible multimodal approach facilitates acute MD detection across multiple clinical applications. Limitations included the observational design, limited statistical power, single-time microvascular measurements, varying illness severity among groups, and possible influences of treatments and vaccinations on MD. Trial registration : Clinical-Trials.gov (NCT04773899).

The study aimed to investigate the connection between an intronic variant in the ABO gene (rs657152) and the severity of COVID-19 in terms of clinical symptoms, haematological complications, inflammatory markers, and lung lesions.

After applying exclusion criteria, the study included 240 patients divided into 3 groups: 88 Outpatients, 84 Ward-hospitalized, and 68 ICU-admitted/failed patients. The tetra-ARMS PCR method was used to genotype ABO polymorphism in the patient. Paraclinical tests of patients at the time of admission (before receiving conventional treatments) included levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as a complete blood count (CBC). Also, the severity of lung lesions was evaluated based on the results of spiral computed tomography (CT) of the chest during admission.

The statistical analysis using the ANOVA test revealed significant differences in the mean values of allele frequencies (p-value = 0.0020) and genotype proportions (p-value = 0.0017) among clinical groups. The study also found a notable difference in ABO polymorphism across different levels of the inflammatory marker CRP, but not with the ESR levels. Furthermore, the study showed a significant difference in the distribution of lung lesion severity and ABO polymorphism among different clinical groups.

To conclude, our findings supported the substantial impact of ABO polymorphism rs657152 on the severity of COVID-19 in Iranian patients, specifically concerning haematological complications, inflammatory markers, and lung lesions. The study underscored the protective effect of the AC genotype and the detrimental impact of the CC genotype on clinical manifestations.

Previous studies have shown that patients with pre-existing chronic obstructive pulmonary diseases (COPD) were more likely to be infected with coronavirus disease (COVID-19) and lead to more severe lung lesions. However, few studies have explored the severity and prognosis of COVID-19 patients with different phenotypes of COPD.

The aim of this study is to investigate the value of the deep learning and radiomics features for the severity evaluation and the nucleic acid turning-negative time prediction in COVID-19 patients with COPD including two phenotypes of chronic bronchitis predominant patients and emphysema predominant patients.

A total of 281 patients were retrospectively collected from Hohhot First Hospital between October 2022 and January 2023. They were divided to three groups: COVID-19 group of 95 patients, COVID-19 with emphysema group of 94 patients, COVID-19 with chronic bronchitis group of 92 patients. All patients underwent chest computed tomography (CT) scans and recorded clinical data. The U-net model was pretrained to segment the pulmonary involvement area on CT images and the severity of pneumonia were evaluated by the percentage of pulmonary involvement volume to lung volume. The 107 radiomics features were extracted by pyradiomics package. The Spearman method was employed to analyze the correlation of the data and visualize it through a heatmap. Then we establish a deep learning model (model 1) and a fusion model (model 2) combined deep learning with radiomics features to predict nucleic acid turning-negative time.

COVID-19 patients with emphysema was lowest in the lymphocyte count compared to COVID-19 patients and COVID-19 companied with chronic bronchitis, and they have the most extensive range of pulmonary inflammation. The lymphocyte count was significantly correlated with pulmonary involvement and the time for nucleic acid turning negative (r=-0.145, P < 0.05). Importantly, our results demonstrated that model 2 achieved an accuracy of 80.9% in predicting nucleic acid turning-negative time.

The pre-existing emphysema phenotype of COPD severely aggravated the pulmonary involvement of COVID-19 patients. Deep learning and radiomics features may provide more information to accurately predict the nucleic acid turning-negative time, which is expected to play an important role in clinical practice.

Airborne pathogen scan penetrate in human respiratory tract and can cause illness. The use of animal models to predict aerosol deposition and study respiratory disease pathophysiology is therefore important for research and a prerequisite to test and study the mechanism of action of treatment. NHPs are relevant animal species for inhalation studies because of their similarities with humans in terms of anatomical structure, respiratory parameters and immune system.

The aim of this review is to provide an overview of the state of the art of pathogen aerosol studies performed in non-human primates (NHPs). Herein, we present and discuss the deposition of aerosolized bacteria and viruses. In this review, we present important advantages of using NHPs as model for inhalation studies.

We demonstrate that deposition in the respiratory tract is not only a function of aerosol size but also the technique of administration influences the biological activity and site of aerosol deposition. Finally, we observe an influence of a region of pathogen deposition in the respiratory tract on the development of the pathophysiological effect in NHPs.

The wide range of methods used for the delivery of pathogento NHP respiratory airways is associated with varying doses and deposition profiles in the airways.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19.

Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25-100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs).

The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47-2.64]; P = .81), nor did organ dysfunction or secondary outcomes.

Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19.

NCT04606563.

In the SARSCov2 virus epidemic, pregnant women are more susceptible to infectious diseases due to changes in biochemical parameters and are at higher risk of severe respiratory disease and pneumonia. This study aimed to evaluate the biochemical, inflammatory and coagulation parameters in pregnant women with severe disease conditions (as one of the high-risk groups) as well as prognosis and outcome.

This cross-sectional study was performed on 135 pregnant women with COVID-19 admitted to ICU. Demographic and clinical information and laboratory parameters of the patients were evaluated and recorded at the time of admission and in the next follow-up until discharge or death in addition to the outcome and also the pregnancy outcome.

The mortality rate of pregnant women with COVID-19 was 9.6%. The mortality rate decreases with increasing Hb (OR (95% CI): 0.68 (0.47-0.99); P value = 0.043) and lymphocytes (OR (95% CI): 0.92 (0.85-0.96); P value = 0.028) and will increase significantly with increasing PT (OR (95% CI): 1.24 (1.01-1.51); P value = 0.037), INR (OR (95% CI): 1.89 (1.26-2.25); P value = 0.004), D-dimer (OR (95% CI): 1.68 (1.10-2.08); P value = 0.027), and LDH (OR (95% CI): 1.20 (1.01-1.61); P value = 0.010).

According to the results of the present study, inflammatory factors such as leukocytes, neutrophils, NLR, CRP have an increasing and lymphocytes have a decreasing trend, so that lymphocytopenia is more common in non-survivors. In addition, increase of PT, INR, D-dimer and LDH and decrease of Hb were significantly associated with increased chance of mortality. But fibrinogen, ferritin, ALT and AST were not significantly associated with mortality in these women.

This comprehensive review articulates critical insights into the nexus of environmental stressors and their health impacts across diverse species, underscoring significant findings that reveal profound effects on both wildlife and human health systems. Central to our examination is the role of pollutants, climate variables, and pathogens in contributing to complex disease dynamics and physiological disruptions, with particular emphasis on immune and endocrine functions. This research brings to light emerging evidence on the severe implications of environmental pressures on a variety of taxa, including predatory mammals, raptorial birds, seabirds, fish, and humans, which are pivotal as indicators of broader ecosystem health and stability. We delve into the nuanced interplay between environmental degradation and zoonotic diseases, highlighting novel intersections that pose significant risks to biodiversity and human populations. The review critically evaluates current methodologies and advances in understanding the morphological, histopathological, and biochemical responses of these organisms to environmental stressors. We discuss the implications of our findings for conservation strategies, advocating for a more integrated approach that incorporates the dynamics of zoonoses and pollution control. This synthesis not only contributes to the academic discourse but also aims to influence policy by aligning with the Global Goals for Sustainable Development. It underscores the urgent need for sustainable interactions between humans and their environments, which are critical for preserving biodiversity and ensuring global health security. By presenting a detailed analysis of the interdependencies between environmental stressors and biological health, this review highlights significant gaps in current research and provides a foundation for future studies aimed at mitigating these pressing issues. Our study is significant as it proposes integrative and actionable strategies to address the challenges at the intersection of environmental change and public health, marking a crucial step forward in planetary health science.

The Spike of SARS-CoV-2 recognizes a transmembrane protease, angiotensin-converting enzyme 2 (ACE2), on host cells to initiate infection. Soluble derivatives of ACE2, in which Spike affinity is enhanced and the protein is fused to Fc of an immunoglobulin, are potent decoy receptors that reduce disease in animal models of COVID-19. Mutations were introduced into an ACE2 decoy receptor, including adding custom N-glycosylation sites and a cavity-filling substitution together with Fc modifications, which increased the decoy's catalytic activity and provided small to moderate enhancements of pharmacokinetics following intravenous and subcutaneous administration in humanized FcRn mice. Most prominently, sialylation of native glycans increases exposures by orders of magnitude, and the optimized decoy is therapeutically efficacious in a mouse COVID-19 model. Ultimately, an engineered and highly sialylated decoy receptor produced using methods suitable for manufacture of representative drug substance has high exposure with a 5- to 9-day half-life. Finally, peptide epitopes at mutated sites in the decoys generally have low binding to common HLA class II alleles and the predicted immunogenicity risk is low. Overall, glycosylation is a critical molecular attribute of ACE2 decoy receptors and modifications that combine tighter blocking of Spike with enhanced pharmacokinetics elevate this class of molecules as viable drug candidates.

A significant hurdle in untargeted lipid/metabolomics research lies in the absence of reliable, cross-validated spectral libraries, leading to a considerable portion of LC-MS features being labeled as unknowns. Despite continuous advancement in annotation tools and libraries, it is important to safeguard, publish and share acquired data through public repositories. Embracing this trend of data sharing not only promotes efficient resource utilization but also paves the way for future repurposing and in-depth analysis; ultimately advancing our comprehension of Covid-19 and other diseases. In this work, we generated an extensive MS-dataset of 39 Covid-19 infected patients versus age- and gender-matched 39 healthy controls. We implemented state of the art acquisition techniques including IDA and SWATH-DIA to ensure a thorough insight in the lipidome and metabolome, ensuring a repurposable dataset.

COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19. We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: "early death" (<15 days until death) and "late death" (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2+ macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2+ epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (TH17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, TH2 responses, and anti-inflammatory-mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes.

Plasma proteomics is a precious tool in human disease research but requires extensive sample preparation in order to perform in-depth analysis and biomarker discovery using traditional data-dependent acquisition (DDA). Here, we highlight the efficacy of combining moderate plasma prefractionation and data-independent acquisition (DIA) to significantly improve proteome coverage and depth while remaining cost-efficient. Using human plasma collected from a 20-patient COVID-19 cohort, our method utilizes commonly available solutions for depletion, sample preparation, and fractionation, followed by 3 liquid chromatography-mass spectrometry/MS (LC-MS/MS) injections for a 360 min total DIA run time. We detect 1321 proteins on average per patient and 2031 unique proteins across the cohort. Differential analysis further demonstrates the applicability of this method for plasma proteomic research and clinical biomarker identification, identifying hundreds of differentially abundant proteins at biological concentrations as low as 47 ng/L in human plasma. Data are available via ProteomeXchange with the identifier PXD047901. In summary, this study introduces a streamlined, cost-effective approach to deep plasma proteome analysis, expanding its utility beyond classical research environments and enabling larger-scale multiomics investigations in clinical settings. Our comparative analysis revealed that fractionation, whether the samples were pooled or separate postfractionation, significantly improved the number of proteins quantified. This underscores the value of fractionation in enhancing the depth of plasma proteome analysis, thereby offering a more comprehensive landscape for biomarker discovery in diseases such as COVID-19.

Hand, foot, and mouth disease (HFMD) is a prevalent infectious affliction primarily affecting children, with a small portion of cases progressing to neurological complications. Notably, in a subset of severe HFMD cases, neurological manifestations may result in significant sequelae and pose a risk of mortality. We systematically conducted literature retrieval from the databases PubMed (1957-2023), Embase (1957-2023), and Web of Science (1957-2023), in addition to consulting authoritative guidelines. Subsequently, we rigorously selected the most relevant articles within the scope of this review for comprehensive analysis. It is widely recognized that the severity of HFMD is attributed to a multifaceted array of pathophysiological mechanisms. The implication of multi-system dysfunction appears to be perturbances of the human defense system; therefore, it contributes to the severity of HFMD. In this review, we provide an overview and analysis of recent insights into the molecular mechanisms contributing to the severity of HFMD, with a particular focus on cytokine release syndrome, the involvement of the renin-angiotensin system, regional immunity, endothelial dysfunction, catecholamine storm, viral invasion, and the molecular mechanisms of neurological damage. We speculate that the domino effect of diverse physiological systems, initiated by damage to the central nervous system, serve as the primary mechanisms governing the severity of HFMD. Simultaneously, we emphasize the knowledge gaps and research urgently required to delineate a quick roadmap for ongoing and essential studies on HFMD.

This study was performed to identify predictive markers of worse outcomes in patients with severe COVID-19 in an intensive care unit.

Sixty patients with severe COVID-19, hospitalized in the Intensive Care Unit (ICU) between March and July 2021, were stratified into two groups according to the outcome survivors and non-survivors. After admission to the ICU, blood samples were collected directly for biomarker analysis. Routine hematological and biochemical biomarkers, as well as serum levels of cytokines, chemokines, and immunoglobulins, were investigated.

Lymphopenia, neutrophilia, and thrombocytopenia were more pronounced in non-surviving patients, while the levels of CRP, AST, creatinine, ferritin, AST, troponin I, urea, magnesium, and potassium were higher in the non-surviving group than the survival group. In addition, serum levels of IL-10, CCL2, CXCL9, and CXCL10 were significantly increased in patients who did not survive. These changes in the biomarkers evaluated were associated with increased mortality in patients with severe COVID-19.

The present study confirmed and expanded the validity of laboratory biomarkers as indicators of mortality in severe COVID-19.

Chest injury is an important factor regarding the prognosis of patients with polytrauma (PT), and the rapid diagnosis of chest injury is of utmost importance. Therefore, the current study focused on patients' physiology and laboratory findings to quickly identify PT patients with chest injury.

Data on 64 PT patients treated at a trauma center level I between June 2020 and August 2021 were retrospectively collected. The patients were divided into a PT group without chest injury (Group A) and a PT group including chest injury (Group B). The relationship between chest injury and the patients' baseline characteristics and biochemical markers was analyzed.

Heart rate, respiration rate, Sequential Organ Failure Assessment (SOFA) score, glutamate oxaloacetate aminotransferase (GOT), glutamate pyruvate transaminase (GPT), creatine kinase MB (CK-MB), leucocytes, hemoglobin (Hb), platelets, urine output, lactate, and lactate dehydrogenase (LDH) in groups A and B exhibited statistically significant differences at certain time points. Multifactorial analysis showed that blood LDH levels at admission were associated with chest injury (P = 0.039, CI 95% 1.001, 1.022).

LDH may be a promising indicator for screening for the presence of chest injury in patients with severe polytrauma.

As a key enzyme of the renin-angiotensin system (RAS), angiotensin-converting enzyme 2 (ACE2) is a validated receptor for SARS-CoV-2, linking RAS to COVID-19. Functional ACE1/ACE2 gene polymorphisms likely cause an imbalance in the ACE1/ACE2 ratio, triggering RAS imbalance and may contribute to COVID-19 complications. This study aimed to investigate four single nucleotide polymorphisms (SNPs) of ACE1 and ACE2 genes, three for ACE1 (rs4343, rs4342, rs4341) and one for ACE2 (rs2285666), in patients with COVID-19 among the Palestinian population. A total of 130 blood samples were collected, including 50 negative controls without COVID-19 infection, 50 cases with COVID-19 infection but not hospitalized, and 30 patients with severe COVID-19 infection hospitalized in the intensive care unit. Fragments of the ACE1 and ACE2 genes, including the targeted SNPs, were amplified using multiplex PCR and subsequently genotyped by next-generation sequencing with specific virtual probes. Our results revealed that ACE2 rs2285666 GG genotype carriers were more prevalent in COVID-19 patients compared to the control group (P=0.049), while no statistical differences were observed in the distribution of ACE1 (rs4343, rs4342, rs4341) variants between COVID-19 patients and the control group. GA carriers of ACE2, rs2285666, among cases and ICU groups were at lower risk of getting COVID-19 infection (P=0.002 and P=0.013, respectively), and they were unlikely to develop fatigue (P=0.043), headache (P=0.007), loss of smell (P=0.028), and dyspnea (P=0.005). Age and comorbidities such as hypertension and coronary artery disease (CAD) were independent risk factors for COVID-19 disease. Symptoms of COVID-19 patients such as fatigue, headaches, runny noses, and loss of smell were significantly higher in non-hospitalized cases of COVID-19, while dyspnea was more frequent in the ICU patients. In conclusion, these findings indicate that the ACE2 rs2285666 GG genotype is associated with an increased risk of COVID-19 infection. This association suggests a potential genetic predisposition linked to the ACE2 gene, which may influence the susceptibility and severity of the disease.

Background: The COVID-19 virus not only has significant pathogenicity but also influences the progression of many diseases, altering patient prognosis. Cardiovascular diseases, particularly aortic aneurysms, are among the most life-threatening conditions. Main Idea: COVID-19 infection is reported to accelerate the progression of abdominal aortic aneurysms (AAAs) and increase the risk of rupture; however, a comprehensive understanding of the underlying mechanisms remains elusive. This article primarily reviews the relevant foundational research, focusing on disruptions in the renin-angiotensin-aldosterone system (RAAS), immune system activation, and coagulation disorders. Furthermore, we summarize related clinical research, including the epidemiology of aortic aneurysms during the pandemic and specific case studies. Conclusion: COVID-19 infection can influence the onset and progression of aortic aneurysms by affecting the RAAS, triggering inflammation and immune dysregulation in the arterial wall, and inducing a hypercoagulation state. It is crucial to comprehensively understand the impact of pandemic viral infections on aortic diseases at the foundational and clinical levels, thereby identifying potential preventative or therapeutic approaches and preparing for potential future outbreaks.

Objective: Observational studies show the correlation between COVID-19 and venous thromboembolism (VTE) risk. However, the causal effects remain uncertain. We aimed to explore the potential causal association between COVID-19 and VTE using Mendelian randomization (MR) design. Methods: Two-sample MR was used to evaluate the potential causality between COVID-19 and VTE by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The weighted median, MR-Egger, simple mode, and weighted mode were employed as supplementary methods for MR estimations, with the inverse-variance weighted (IVW) method serving as the principal analysis. In addition, we took sensitivity analyses, including Cochran's test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to ensure that we obtained stable and reliable results. Results: Our study selected 26 COVID-19 severity, 31 COVID-19 hospitalization, and 13 COVID-19 susceptibility SNPs as instrumental variables. The IVW analysis results revealed that there was no causal relationship between COVID-19 severity, hospitalization, or susceptibility and VTE, with odds ratios of 0.974 (95%CI: 0.936-1.013, p = 0.19), 0.976 (95%CI: 0.918-1.039, p = 0.447), and 0.908 (95%CI: 0.775-1.065, p = 0.235), respectively. The IVW approach yielded consistent results with MR-Egger, Weighted Median simple mode, and weighted mode. MR-PRESSO and sensitivity analysis further confirmed the stability and consistency of the MR results. Conclusions: This study did not find evidence to support a causal relationship between COVID-19 and VTE at the genetic level. Further investigation is warranted to determine if the significant association reported in previous observational studies between the two is due to confounding factors.

Coronavirus disease 2019 (COVID-19), a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a global health threat. The virus enters host cells by binding with angiotensin-converting enzyme 2 (ACE2), which is then facilitated by the protease activity of transmembrane serine protease 2 (TMPRSS2). It triggers a cytokine storm that eventually leads to cell apoptosis, tissue damage, and organ failure. Therefore, any organs in the human body that have both receptors are highly susceptible to COVID-19 infection, potentially resulting in multiple-organ failure. The prostate has been reported to express high levels of ACE2 and TMPRSS2. While there are limited studies regarding the association between COVID-19 and prostatitis, the possibility that SARS-CoV-2 could cause prostatitis cannot be denied. Thus, through this review, a better insight into the associations of SAR-CoV-2 can be provided.

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.