Air pollution is a major global environment and health concern. Recent studies have suggested an association between air pollution and COVID-19 mortality and morbidity. In this context, a close association between increased levels of air pollutants such as particulate matter ≤2.5 to 10 µM, ozone and nitrogen dioxide and SARS-CoV-2 infection, hospital admissions and mortality due to COVID 19 has been reported. Air pollutants can make individuals more susceptible to SARS-CoV-2 infection by inducing the expression of proteins such as angiotensin converting enzyme (ACE)2 and transmembrane protease, serine 2 (TMPRSS2) that are required for viral entry into the host cell, while causing impairment in the host defence system by damaging the epithelial barrier, muco-ciliary clearance, inhibiting the antiviral response and causing immune dysregulation. The aim of this review is to report the epidemiological evidence on impact of air pollutants on COVID 19 in an up-to-date manner, as well as to provide insights on in vivo and in vitro mechanisms.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to a significant burden on global healthcare systems. COVID-19-induced acute kidney injury (AKI) is among one of the complications, that has emerged as a critical and frequent condition in COVID-19 patients. This AKI among COVID-19 patients is associated with poor outcomes, and high mortality rates, especially in those with severe AKI or requiring renal replacement therapy. COVID-19-induced AKI represents a significant complication with complex pathophysiology and multifactorial risk factors. Indeed, several pathophysiological mechanisms, including direct viral invasion of renal cells, systemic inflammation, endothelial and thrombotic abnormalities as well as nephrotoxic drugs and rhabdomyolysis are believed to underlie this condition. Moreover, histopathological and immunohistopathological findings commonly observed in postmortem studies include acute tubular necrosis, glomerular injury, and the presence of viral particles within renal tissue and urine. Identified risk factors for developing AKI vary among studies, depending on regions, underlying conditions, and the severity of the disease. Moreover, histopathological and immunohistopathological findings commonly observed in postmortem studies include show acute tubular necrosis, glomerular injury, and viral particles within renal tissue and urine. While, identified risk factors for developing AKI vary among studies, according to regions, underlying conditions, and the gravity of the disease. This narrative review aims to synthesize current knowledge on the incidence, pathophysiology, risk factors, histopathology, and outcomes of AKI induced by COVID-19.

Bulk RNA sequencing is one type of RNA sequencing technique, as well as targeted RNA sequencing and whole transcriptome sequencing. It provides valuable insights into gene expression in specific cell populations or regions. However, these methods often miss the diversity of cells within complex tissues. This restriction is overcome by single-cell RNA sequencing, which records gene expression at the single-cell level. It offers a detailed picture of the diversity of cells. It is essential to study glucose homeostasis. It offers thorough explanations of cellular variation. Networks and Governance Dynamics The use of scRNA-seq in islet cells is reviewed in this study, along with sample preparation, sequencing, and computational analysis. It highlights advances in understanding cell types. Gene activity and cell interactions. Along with the challenges and limitations of scRNA-seq, this review highlights the importance of scRNA-seq in understanding complex biological processes and diseases. It is an essential resource for future research and method development in this field, which will help to build personalized treatment.

SARS-CoV-2 infection has been responsible of COrona VIrus Disease (COVID-19) pandemia and can cause a variety of symptoms including gastrointestinal disorders, abdominal pain and liver injury. The host receptor for SARS-CoV-2, ACE2, is expressed in gut and SARS-CoV-2 infection could induce vascular damage and immune system dysregulation, creating an inflammatory and hypercoagulable state, as widely described at the lung level.

This work presents the case of a middle-aged Caucasian man admitted to the Hospital Emergency Department from the University Hospital of Ferrara (Italy), complaining of pain in the upper and middle region of the abdomen. The patient tested negative to the nose-oropharyngeal swab for SARS-CoV-2 four weeks after recovering from viral infection. The patient required resection of a segment of ileum and an ulcer of the bowel wall was recognized and sampled. Previous published results had confirmed the presence of the SARS-CoV-2 nucleocapsid protein, an increased human leukocyte antigen (HLA-G) and an altered morphology of microvilli in the ulcerated ileum of the patient when compared to the non-ulcerated ileum. The present study sought to deepen the consequences of SARS-CoV-2 infection. To this end, we evaluated the expression and co-expression of Vascular Endothelial Growth Factor (VEGF) and Fibronectin by immunohistochemical techniques. VEGF immunohistochemical expression was higher in the ulcer than in the control ileum sample and the non-ulcerated ileum areas and co-expressed with the SPIKE protein. Fibronectin staining was lower in control sample than in non-ulcerated and ulcerated ileum. Electron microscopy analysis showed alterations of the integrity of the intestinal barrier in the ulcerated area when compared to the non-ulcerated ileum or to the control sample.

Although the patient was tested negative to nose-oropharyngeal swab for SARS-CoV-2, the SPIKE protein was detected in his terminal ileum, especially in the ulcerated areas. The presence of the viral protein was also associated with an increase of VEGF and Fibronectin. In addition to vascular changes, the SARS-CoV-2 infection altered the junctional apparatus among epithelial cells, making the tissue even more fragile and thus susceptible to the entry of pathogens and the development of further infections.

Respiratory viral infections are a major global public health concern, and current antiviral therapies still have limitations. In recent years, research has revealed significant similarities between the immune systems of the gut and lungs, which interact through the complex physiological network known as the "gut-lung axis." As one of the largest immune organs, the gut, along with the lungs, forms an inter-organ immune network, with strong parallels in innate immune mechanisms, such as the activation of pattern recognition receptors (PRRs). Furthermore, the gut microbiota influences antiviral immune responses in the lungs through mechanisms such as systemic transport of gut microbiota-derived metabolites, immune cell migration, and cytokine regulation. Studies have shown that gut dysbiosis can exacerbate the severity of respiratory infections and may impact the efficacy of antiviral therapies. This review discusses the synergistic role of the gut-lung axis in antiviral immunity against respiratory viruses and explores potential strategies for modulating the gut microbiota to mitigate respiratory viral infections. Future research should focus on the immune mechanisms of the gut-lung axis to drive the development of novel clinical treatment strategies.

Cell-cell interaction (CCI) networks are key to understanding disease progression and treatment response. However, existing methods for inferring these networks often aggregate data across patients or focus on cell-type level interactions, providing a generalized overview but overlooking patient heterogeneity and local network structures. To address this, we introduce "random cell-cell interaction generator" (RaCInG), a model based on random graphs to derive personalized networks leveraging prior knowledge on ligand-receptor interactions and bulk RNA sequencing data. We applied RaCInG to 8,683 cancer patients to extract 643 network features related to the tumor microenvironment and unveiled associations with immune response and subtypes, enabling prediction and explanation of immunotherapy responses. RaCInG demonstrated robustness and showed consistencies with state-of-the-art methods. Our findings highlight RaCInG's potential to elucidate patient-specific network dynamics, offering insights into cancer biology and treatment responses. RaCInG is poised to advance our understanding of complex CCI s in cancer and other biomedical domains.

Long COVID or Post-acute sequelae of COVID-19 is an emerging syndrome, recognized in COVID-19 patients who suffer from mild to severe illness and do not recover completely. Most studies define Long COVID, through symptoms like fatigue, brain fog, joint pain, and headache prevailing four or more weeks post-initial infection. Global variations in Long COVID presentation and symptoms make it challenging to standardize features of Long COVID. Long COVID appears to be accompanied by an auto-immune multi-faceted syndrome where the virus or viral antigen persistence causes continuous stimulation of the immune response, resulting in multi-organ immune dysregulation.

This review is focused on understanding the risk factors of Long COVID with a special emphasis on the dysregulation of the gut-brain axis. Two proposed mechanisms are discussed here. The first mechanism is related to the dysfunction of angiotensin-converting enzyme 2 receptor due to Severe Acute Respiratory Syndrome Corona Virus 2 infection, leading to impaired mTOR pathway activation, reduced AMP secretion, and causing dysbiotic changes in the gut. Secondly, gut-brain axis dysregulation accompanied by decreased production of short-chain fatty acids, impaired enteroendocrine cell function, and increased leakiness of the gut, which favors translocation of pathogens or lipopolysaccharide in circulation causing the release of pro-inflammatory cytokines. The altered Hypothalamic-Pituitary-Adrenal axis is accompanied by the reduced level of neurotransmitter, and decreased stimulation of the vagus nerve, which may cause neuroinflammation and dysregulation of serum cortisol levels. The dysbiotic microbiome in Long COVID patients is characterized by a decrease in beneficial short chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcus, Dorea, and Bifidobacterium) and an increase in opportunistic bacteria (Corynebacterium, Streptococcus, Enterococcus). This dysbiosis is transient and may be impacted by interventions including probiotics, and dietary supplements.

Further studies are required to understand the geographic variation, racial and ethnic differences in phenotypes of Long COVID, the influence of viral strains on existing and emerging phenotypes, to explore long-term effects of gut dysbiosis, and gut-brain axis dysregulation, as well as the potential role of diet and probiotics in alleviating those symptoms.

This study examined the incidence, characteristics, and risk factors of new gastrointestinal disorders (GID) associated with SARS-CoV-2 infection up to 3.5 years post-infection. This retrospective study included 35,102 COVID-19 patients and 682,594 contemporary non-COVID-19 patients without past medical history of GID (controls) from the Montefiore Health System in the Bronx (3/1/2020 to 7/31/2023). Comparisons were made with unmatched and propensity-matched (1:2) controls. The primary outcome was new GID which included peptic ulcer, inflammatory bowel disease, irritable bowel syndrome, diverticulosis, diverticulitis, and biliary disease. Multivariate Cox proportional hazards model analysis was performed with adjustment for covariates. There were 2,228 (6.34%) COVID-19 positive patients who developed new GID compared to 38,928 (5.70%) controls. COVID-19 patients had an elevated risk of developing new GID (adjusted HR = 1.18 (95% CI 1.12-1.25) compared to propensity-matched controls, after adjusting for confounders that included smoking, obesity, diabetes, hypertension. These findings underscore the need for additional research and follow-up of at-risk individuals for developing GID post infection.

COVID-19 and hepatitis B disease are significant global pandemics, both of which can lead to liver damage. This study aims to report the clinical course of liver function and disease prognosis of COVID-19 patients with hepatitis B virus (HBV) super-infections. A total of 249 outpatients with COVID-19 were enrolled in this study from December 1, 2023 to February 28, 2024. Clinical characteristics, laboratory data, chest CT findings, and patients' treatment and outcomes were collected and analyzed retrospectively. Of the 249 outpatients, 37 (14.9%) were super-infected with HBV, whereas 212 (85.1%) showed no such outcome. This study found no significant differences between the two groups regarding age, gender, symptoms, complications, or chest CT findings. However, COVID-19 patients super-infected with HBV showed lower white blood cell, neutrophil, and platelet counts (p < 0.05). Additionally, total bilirubin levels were significantly higher in the SARS-CoV-2/HBV super-infected group compared to the COVID-19-only group (p = 0.022). After the first week of similar treatment, both groups showed almost identical outcomes, including hospitalization, severity, and mortality rates. Thus, SARS-CoV-2/HBV super-infection slightly affected liver function but did not worsen COVID-19 outcomes. Routine HBV monitoring and liver function tests are recommended to manage COVID-19 patients with HBV super-infections. This study found no clear indications of the need to change the therapeutic prescription for COVID-19 in cases of HBV super-infections.

The Coronavirus Disease 2019 (COVID-19) pandemic, driven by the novel coronavirus and its variants, has caused over 518 million infections and 6.25 million deaths globally, leading to a significant health crisis. Beyond its primary respiratory impact, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been implicated in various extra-pulmonary complications. Research studies reveal that the virus affects multiple organs, including the kidneys, liver, pancreas, and central nervous system (CNS), largely due to the widespread expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors. Clinical evidence shows that the virus can induce diabetes by disrupting pancreatic and liver functions as well as cause acute kidney injury. Additionally, neurological complications, including cognitive impairments and neuroinflammation, have been observed in a significant number of COVID-19 patients. This review discusses the mechanisms linking SARS-CoV-2 to acute kidney injury, Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM), emphasizing its effects on pancreatic beta cells, insulin resistance, and the regulation of gluconeogenesis. We also explore how SARS-CoV-2 induces neurological complications, detailing the intricate pathways of neuro-invasion and the potential to trigger conditions such as Alzheimer's disease (AD). By elucidating the metabolic and neurological manifestations of COVID-19 and the underlying pathogenic mechanisms, this review underscores the imperative for continued research and the development of effective therapeutic interventions to mitigate the long-term and short-term impacts of SARS-CoV-2 infection.

The COVID-19 pandemic has prompted the exploration of effective treatment options, with dexamethasone emerging as a key corticosteroid for severe cases. This review evaluates the efficacy and safety of dexamethasone, highlighting its ability to reduce mortality rates, alleviate acute respiratory distress syndrome (ARDS), and mitigate hyperinflammation. While dexamethasone shows therapeutic promise, potential adverse effects-including cardiovascular issues, neuropsychiatric complications, lung infections, and liver damage-necessitate careful monitoring and individualized treatment strategies. The review also addresses the debate over using dexamethasone alone versus in combination with other therapies targeting SARS-CoV-2, examining potential synergistic effects and drug resistance. In summary, dexamethasone is a valuable treatment option for COVID-19 but its risks highlight the need for tailored surveillance approaches. Further research is essential to establish clear guidelines for optimizing treatment and improving patient outcomes.

Despite herbal medicine being popular across the Mediterranean basin, there is no evidence in favor of COVID-19 infection. This study investigates the utilization and effects of medicinal plants in Italy, Lebanon, and Tunisia during COVID-19 and its effects on post-COVID-19 pandemics. We used a tailored, web-based "Google Form" questionnaire with the random sampling method. We gathered 812 complete responses (Italy: 116, Lebanon: 557, and Tunisia: 139), revealing diverse demographics and symptom experiences. Fatigue prevailed across all groups (89.0-94.2%), while psychological impacts ranged from 20.1% to 30.9%, with higher rates in Lebanon. Post-COVID-19 symptoms affected 22.4% (Italy), 48.8% (Lebanon), and 31.7% (Tunisia). General use of herbs was consistent (41.4-50.4%), with 23.3% (Italy), 50.2% (Lebanon), and 65.5% (Tunisia) employing herbs for COVID-19 therapy. Notably, in Lebanon, Za'atar, a thyme-like plant, correlated with reduced symptoms, suggesting potential protective effects that are likely due to its polyphenol richness. This study underscores the persistent reliance on traditional medicinal plants remedies in the Mediterranean area, with regional variations. Further exploration of herbal compounds for COVID-19-like symptoms is warranted.

Infection during pregnancy with SARS-CoV-2 can have a serious impact on both maternal and foetal health. Clinical studies have shown that SARS-CoV-2 transmission from the mother to the foetus typically does not occur. However, there is evidence that SARS-CoV-2 can infect the placenta in utero. Here we sought to quantify the permissiveness of placental cells to SARS-CoV-2 infection and to determine if they support viral release.

By using publicly available single-cell RNA sequencing (scRNAseq) data sets and confocal microscopy we compared ACE2 transcript and protein expression across human first trimester and term placental cells. We also used in vitro infection assays to quantify the infection rates of a range of placenta-derived cells. Finally, we quantified the viral egress from these cells.

ACE2 transcripts are found in a range of placental cell types across gestation, including trophoblast. However, ACE2 protein expression does not significantly change across placental cell types from first trimester to term. We find that 0.5±0.15 % of term trophoblast cells can be infected with SARS-CoV-2 while primary placental fibroblasts and macrophages, and JEG-3, JAR and HUVEC cell lines are resistant to infection. Furthermore, primary trophoblast cells poorly support viral release while JEG-3 cells allow relatively high levels of viral release.

The low level of viral release by primary placental cells provides insight into how the virus is impaired from crossing the placenta to the foetus.

Viruses are obligate intracellular parasites, and they exploit the cellular pathways and resources of their respective host cells to survive and successfully multiply. The strategies of viruses concerning how to take advantage of the metabolic capabilities of host cells for their own replication can vary considerably. The most common metabolic alterations triggered by viruses affect the central carbon metabolism of infected host cells, in particular glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. The upregulation of these processes is aimed to increase the supply of nucleotides, amino acids, and lipids since these metabolic products are crucial for efficient viral proliferation. In detail, however, this manipulation may affect multiple sites and regulatory mechanisms of host-cell metabolism, depending not only on the specific viruses but also on the type of infected host cells. In this review, we report metabolic situations and reprogramming in different human host cells, tissues, and organs that are favorable for acute and persistent SARS-CoV-2 infection. This knowledge may be fundamental for the development of host-directed therapies.

Liver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities was not sufficiently addressed in the study areas. Therefore, the current study aimed to investigate the effects of COVID-19 infection on liver function of patients.

A facility-based comparative cross-sectional study was carried out from 10 April to 15 June 2022, among COVID-19 infected individuals admitted in Eka Kotebe General Hospital and Saint Petrous Specialized Hospitals, Addis Ababa, 2022.

A total of 284 confirmed COVID-19-positive and COVID-19-negative controls matched by gender and age were included in the present study.

Among SARS-COV-2 positive groups, 63 (44.4%) had one or more LFT abnormalities. The most common elevated level of the LFTs among patients with COVID-19 were gamma-glutamyl transferase (GGT) 50 (35.2%), while the most common lowered level was albumin 58 (40.8%). The mean values of aspartate aminotransferase (AST) (35.4±26.9 vs 22.9±12.6, p<0.001) were significantly different between patients with COVID-19 and the COVID-19-free groups. Being COVID-19-positive was significantly associated with an elevated level of AST (AOR=3.0, 95% CI 1.2 to 7.4) and GGT (AOR=4.55, 95% CI 2.02 to 10.3). Being male was significantly associated with an elevated level of total bilirubin (BILT, AOR=2.41, 95% CI 1.2 to 4.9) and direct bilirubin (BILD, AOR=3.7, 95% CI 1.72 to 8.2), and also severe stage of COVID-19 was associated with hypoalbuminaemia (AOR=3.3, 95% CI 1.4 to 7.9). SARS-COV-2 infection was independently associated with LFT abnormality.

Patients with COVID-19 had decreased albumin levels, and elevated AST, GGT, BILT and BILD levels.

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway in productively infected cells. Pharmacological inhibition of STING in primary airway cells enhances SARS-CoV-2 replication and reduces virus-induced innate immune activation. Together, our study highlights that tonic activation of the cGAS-STING and IFN pathways can impact SARS-CoV-2 cellular tropism in a manner dependent on ACE2 expression levels.

Single-cell genomics provide researchers with tools to assess host-pathogen interactions at a resolution previously inaccessible. Transcriptome analysis, epigenome analysis, and immune profiling techniques allow for a better comprehension of the heterogeneity underlying both the host response and infectious agents. Here, we highlight technological advancements and data analysis workflows that increase our understanding of host-pathogen interactions at the single-cell level. We review various studies that have used these tools to better understand host-pathogen dynamics in a variety of infectious disease contexts, including viral, bacterial, and parasitic diseases. We conclude by discussing how single-cell genomics can advance our understanding of host-pathogen interactions.

Coronaviruses rely on host proteases to activate the viral spike protein, which facilitates fusion with the host cell membrane and the release of viral genomic RNAs into the host cell cytoplasm. The distribution of specific host proteases in the host determines the host, tissue, and cellular tropism of these viruses. Here, we identified the kallikrein (KLK) family member KLK5 as a major host protease secreted by human airway cells and exploited by multiple human betacoronaviruses. KLK5 cleaved both the priming (S1/S2) and activation (S2') sites of spike proteins from various human betacoronaviruses in vitro. In contrast, KLK12 and KLK13 displayed preferences for either the S2' or S1/S2 site, respectively. Whereas KLK12 and KLK13 worked in concert to activate SARS-CoV-2 and MERS-CoV spike proteins, KLK5 by itself efficiently activated spike proteins from several human betacoronaviruses, including SARS-CoV-2. Infection of differentiated human bronchial epithelial cells (HBECs) with human betacoronaviruses induced an increase in KLK5 that promoted virus replication. Furthermore, ursolic acid and other related plant-derived triterpenoids that inhibit KLK5 effectively suppressed the replication of SARS-CoV, MERS-CoV, and SARS-CoV-2 in HBECs and mitigated lung inflammation in mice infected with MERS-CoV or SARS-CoV-2. We propose that KLK5 is a pancoronavirus host factor and a promising therapeutic target for current and future coronavirus-induced diseases.

Most healthy individuals recover from acute SARS-CoV-2 infection, whereas a remarkable number continues to suffer from unexplained symptoms, known as Long COVID or post-acute COVID-19 syndrome (PACS). It is therefore imperative that methods for preventing and treating the onset of PASC be investigated with the utmost urgency.

A mathematical model of the immune response to vaccination and viral infection with SARS-CoV-2, incorporating immune memory cells, was developed.

Similar to our previous model, persistent infection was observed by the residual virus in the host, implying the possibility of chronic inflammation and delayed recovery from tissue injury. Pre-infectious vaccination and antiviral medication administered during onset can reduce the acute viral load; however, they show no beneficial effects in preventing persistent infection. Therefore, the impact of these treatments on the PASC, which has been clinically observed, is mainly attributed to their role in preventing severe tissue damage caused by acute viral infections. For PASC patients with persistent infection, vaccination was observed to cause an immediate rapid increase in viral load, followed by a temporary decrease over approximately one year. The former was effectively suppressed by the coadministration of antiviral medications, indicating that this combination is a promising treatment for PASC.

Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

The coronavirus disease (COVID-19) is a widely spread viral infectious disease, which can impact multiple organs, including the liver. Elevated liver enzymes have been reported in COVID-19 patients; however, potential changes in liver stiffness following the viral infection remain uncertain. The main aim of this pilot study was to determine if there is a significant difference in liver stiffness between individuals who have never been infected with COVID-19 and those who had been infected with COVID-19 <6 months, experiencing only mild symptoms. The secondary aim was to compare the liver stiffness between participants infected with COVID-19 depending on the elapsed time since infection.

Two-dimensional shear wave elastography (2D-SWE) was performed prospectively on 68 participants. Thirty-four participants had been infected with COVID-19 (all for <6 months) (COVID-19 group), and another 34 had never been infected with COVID-19 (control group). The mean 2D-SWE measurements of both the COVID-19 group and the control group were compared using an independent t-test. The mean 2D-SWE measurements of the COVID-19 subgroups A (<2 months), B (2 to <4 months) and C (4 to <6 months) were compared using a one-way ANOVA test (P < 0.05).

The (mean ± standard deviation) liver stiffness (kPa) of the COVID-19 group (5.26 ± 1.63 kPa) was significantly higher than the control group (4.30 ± 0.96 kPa) (P = 0.005). There was no significant difference in liver stiffness among subgroups A (5.20 ± 1.79 kPa), B (4.70 ± 1.53 kPa) and C (5.96 ± 1.48 kPa) (P = 0.143) respectively.

The mean liver stiffness of 4.30  ±  0.96k Pa in the control group showed a high probability of being normal as per guidelines. Conversely, the mean liver stiffness of 5.26  ±  1.63 kPa in the COVID-19 group exhibited a statistically significant increase compared to the control group. However, compensated advanced chronic liver disease was ruled out without other known clinical signs, as per guidelines.

A statistically significant increase in liver stiffness value was observed in the post-COVID-19 infection group compared to the group who had never been infected. This highlights the potential for short-term impact on liver stiffness associated with COVID-19 infection. However, it is unclear if these changes in liver stiffness are associated with liver injury. Further study is warranted to investigate the effects of COVID-19 infection and its long-term impact on the liver.

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.

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.

Genomic surveillance based on sequencing the entire genetic code of SARS-CoV-2 involves monitoring and studying genetic changes and variations in disease-causing organisms such as viruses and bacteria. By tracing the virus, it is possible to prevent epidemic spread in the community, ensuring a 'precision public health' strategy. A peptide-based design was applied to provide an efficacious strategy that is able to counteract any emerging viral variant of concern dynamically and promptly to affect the outcomes of a pandemic at an early stage while waiting for the production of the anti-variant-specific vaccine, which require longer times. The inhibition of the interaction between the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and one of the cellular receptors (DPP4) that its receptors routinely bind to infect human cells is an intriguing therapeutic approach to prevent the virus from entering human cells. Among the other modalities developed for this purpose, peptides surely offer unique advantages, including ease of synthesis, serum stability, low immunogenicity and toxicity, and small production and distribution chain costs. Here, we obtained a potent new inhibitor based on the rearrangement of a previously identified peptide that has been rationally designed on a cell dipeptidyl peptidase 4 (DPP4) sequence, a ubiquitous membrane protein known to bind the RBD-SPIKE domain of the virus. This novel peptide (named DPP4-derived), conceived as an endogenous "drug", is capable of targeting the latest tested variants with a high affinity, reducing the VSV* DG-Fluc pseudovirus Omicron's infection capacity by up to 14%, as revealed by in vitro testing in human Calu-3 cells. Surface plasmon resonance (SPR) confirmed the binding affinity of the new DPP4-derived peptide with Omicron variant RBD.

Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC).

The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10.

Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals.

This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.

SARS-CoV-2 causes persistent infections in a subset of individuals, which is a major clinical and public health problem that should be prioritised for further investigation for several reasons. First, persistent SARS-CoV-2 infection often goes unrecognised, and therefore might affect a substantial number of people, particularly immunocompromised individuals. Second, the formation of tissue reservoirs (including in non-respiratory tissues) might underlie the pathophysiology of the persistent SARS-CoV-2 infection and require new strategies for diagnosis and treatment. Finally, persistent SARS-CoV-2 replication, particularly in the setting of suboptimal immune responses, is a possible source of new, divergent virus variants that escape pre-existing immunity on the individual and population levels. Defining optimal diagnostic and treatment strategies for patients with persistent virus replication and monitoring viral evolution are therefore urgent medical and public health priorities.

Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

The renin-angiotensin-aldosterone system (RAAS) holds a position of paramount importance as enzymatic and endocrine homeostatic regulator concerning the water-electrolyte and acid-base balance. Nevertheless, its intricacy is influenced by the presence of various complementary angiotensins and their specific receptors, thereby modifying the primary RAAS actions. Angiotensin-converting enzyme 2 (ACE2) acts as a surface receptor for SARS-CoV-2, establishing an essential connection between RAAS and COVID-19 infection. Despite the recurring exploration of the RAAS impact on the trajectory of COVID-19 along with the successful resolution of many inquiries, its complete role in the genesis of delayed consequences encompassing long COVID and cardiovascular thrombotic outcomes during the post-COVID phase as well as post-vaccination, remains not fully comprehended. Particularly noteworthy is the involvement of the RAAS in the molecular mechanisms underpinning procoagulant processes throughout COVID-19. These processes significantly contribute to the pathogenesis of organ complications as well as determine clinical outcomes and are discussed in this manuscript.

The long COVID (coronavirus disease), a multisystemic condition following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the widespread problems. Some of its symptoms affect the nervous system and resemble symptoms of Alzheimer's disease (AD)-a neurodegenerative condition caused by the accumulation of amyloid beta and hyperphosphorylation of tau proteins. Multiple studies have found dependence between these two conditions. Patients with Alzheimer's disease have a greater risk of SARS-CoV-2 infection due to increased levels of angiotensin-converting enzyme 2 (ACE2), and the infection itself promotes amyloid beta generation which enhances the risk of AD. Also, the molecular pathways are alike-misregulations in folate-mediated one-carbon metabolism, a deficit of Cq10, and disease-associated microglia. Medical imaging in both of these diseases shows a decrease in the volume of gray matter, global brain size reduction, and hypometabolism in the parahippocampal gyrus, thalamus, and cingulate cortex. In some studies, a similar approach to applied medication can be seen, including the use of amino adamantanes and phenolic compounds of rosemary. The significance of these connections and their possible application in medical practice still needs further study but there is a possibility that they will help to better understand long COVID.

The treatment of patients with advanced-stage solid tumours typically involves a multimodality approach (including surgery, chemotherapy, radiotherapy, targeted therapy and/or immunotherapy), which is often ultimately ineffective. Nucleic acid-based drugs, either as monotherapies or in combination with standard-of-care therapies, are rapidly emerging as novel treatments capable of generating responses in otherwise refractory tumours. These therapies include those using viral vectors (also referred to as gene therapies), several of which have now been approved by regulatory agencies, and nanoparticles containing mRNAs and a range of other nucleotides. In this Review, we describe the development and clinical activity of viral and non-viral nucleic acid-based treatments, including their mechanisms of action, tolerability and available efficacy data from patients with solid tumours. We also describe the effects of the tumour microenvironment on drug delivery for both systemically administered and locally administered agents. Finally, we discuss important trends resulting from ongoing clinical trials and preclinical testing, and manufacturing and/or stability considerations that are expected to underpin the next generation of nucleic acid agents for patients with solid tumours.

Although studies evaluated placental involvement in Covid-19 patients, few have assessed its association with clinical repercussions. The study aimed to determine the association between the clinical status and maternal and perinatal outcomes of patients with Covid-19 at delivery and changes in placental histology. It is so far the largest cohort evaluating placentas of patients infected by the SARS-CoV-2. A secondary analysis was conducted of a database from which a cohort of 226 patients, who tested real-time polymerase chain reaction-positive for Covid-19 at delivery and whose placentas were collected and submitted to pathology, was selected for inclusion. One or more types of histological changes were detected in 44.7% of the 226 placentas evaluated. The most common abnormalities were maternal vascular malperfusion (38%), evidence of inflammation/infection (9.3%), fetal vascular malperfusion (0.8%), fibrinoid changes and intervillous thrombi (0.4%). Oxygen use (P = .01) and need for admission to an intensive care unit (ICU) (P = .04) were less common in patients with placental findings, and hospital stay was shorter in these patients (P = .04). There were more fetal deaths among patients with evidence of inflammation/infection (P = .02). Fetal death, albeit uncommon, is associated with findings of inflammation/infection. Oxygen use and need for admission to an ICU were less common among patients with placental findings, probably due to the pregnancy being interrupted early. None of the other findings was associated with maternal clinical status or with adverse perinatal outcome.

With the rapid global spread of COVID-19, it has become evident that the virus can lead to multisystem complications, leading to a significant increase in related publications. Bibliometrics serves as a valuable tool for identifying highly cited literature and research hotspots within specific areas.

The aim of this study is to identify current research hotspots and future trends in COVID-19 complications.

The dataset was obtained from the Web of Science Core Collection, covering COVID-19 complications from December 8, 2019, to October 31, 2022. Various aspects, including publication general information, authors, journals, co-cited authors, co-cited references, research hotspots, and future trends, were subjected to analysis. Visual analysis was conducted using VOSviewer, The Online Analysis Platform of Literature Metrology, and Charticulator.

There were 4597 articles in the study. The top three countries with the most published articles are the USA (n = 1350, 29.4 %), China (n = 765, 16.6 %), and Italy (n = 623, 13.6 %). USA and China have the closest collaborative relationship. The institute with the largest number of publications is Huazhong University of Science and Technology, followed by Harvard Medical School. Nevertheless, half of the top 10 institutes belong to the USA. "Rezaei, Nima" published 13 articles and ranked first, followed by "Yaghi, Shadi" with 12 articles and "Frontera, Jennifer" with 12 articles. The journal with the largest number of publications is "Journal of Clinical Medicine". The top 3 co-cited authors are "Zhou, Fei", "Guan, Wei-Jie", "Huang, Chaolin". The top 3 co-cited references addressed COVID-19's clinical features in China and noticed that COVID-19 patients had a wide range of complications. We also list four research hotspots.

This study conducted a bibliometric visual analysis of the literature on COVID-19 complications and summarized the current research hotspots. This study may provide valuable insights into the complications of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the lung but can also cause gastrointestinal (GI) symptoms. In vitro experiments confirmed that SARS-CoV-2 robustly infects intestinal epithelium. However, data on infection of adult gastric epithelium are sparse and a side-by-side comparison of the infection in the major segments of the GI tract is lacking. We provide this direct comparison in organoid-derived monolayers and demonstrate that SARS-CoV-2 robustly infects intestinal epithelium, while gastric epithelium is resistant to infection. RNA sequencing and proteome analysis pointed to angiotensin-converting enzyme 2 (ACE2) as a critical factor, and, indeed, ectopic expression of ACE2 increased susceptibility of gastric organoid-derived monolayers to SARS-CoV-2. ACE2 expression pattern in GI biopsies of patients mirrors SARS-CoV-2 infection levels in monolayers. Thus, local ACE2 expression limits SARS-CoV-2 expression in the GI tract to the intestine, suggesting that the intestine, but not the stomach, is likely to be important in viral replication and possibly transmission.

The rapid spread of the SARS-CoV-2 virus has emphasized the urgent need for effective therapies to combat COVID-19. Investigating the potential targets, inhibitors, and in silico approaches pertinent to COVID-19 are of utmost need to develop novel therapeutic agents and reprofiling of existing FDA-approved drugs. This article reviews the viral enzymes and their counter receptors involved in the entry of SARS-CoV-2 into host cells, replication of genomic RNA, and controlling the host cell physiology. In addition, the study provides an overview of the computational techniques such as docking simulations, molecular dynamics, QSAR modeling, and homology modeling that have been used to find the FDA-approved drugs and other inhibitors against SARS-CoV-2. Furthermore, a comprehensive overview of virus-based and host-based druggable targets from a structural point of view, together with the reported therapeutic compounds against SARS-CoV-2 have also been presented. The current study offers future perspectives for research in the field of network pharmacology investigating the large unexplored molecular libraries. Overall, the present in-depth review aims to expedite the process of identifying and repurposing drugs for researchers involved in the field of COVID-19 drug discovery.

Children with COVID-19 may present with gastrointestinal (GI) symptoms and liver dysfunction.

To determine the type and prevalence of gastrointestinal (GI) and hepatic manifestations of COVID-19 in children and its association with severity of illness.

A systematic literature search was done from inception until January 4, 2021 using PubMed, Cochrane Library, Google Scholar and prepublication repositories with no language restrictions. Studies that reported the demographic and clinical features of children with COVID-19 and provided data on their GI and hepatic signs and symptoms were included. Prevalence of GI and hepatic manifestations were pooled using Stata14.

We included 58 studies with total of 4497 participants. Overall, one-third of children with COVID-19 presented with at least one GI symptom (33.8%; 95% confidence interval (CI) 23.0, 45.4; I2 97.5%; 42 studies, 3327 participants) with abdominal pain, nausea or vomiting, and diarrhea each occurring in approximately 20%. Children with severe COVID-19 were more likely to present with GI symptoms (odds ratio 2.59; 95% CI 1.35, 4.99; I2 24%; 4 studies, 773 participants). The pooled prevalence of elevated transaminases was 11% for both AST (11.3%, 95% CI 4.9, 19.3; I2 74.7%; 11 studies, 447 participants) and ALT (11.2%, 95% CI 7.1, 16.0; I2 40.8%; 15 studies, 513 participants). Hepatic findings such as jaundice (2-17%), hepatomegaly (2%) or behavioral changes (2%) from hepatic encephalopathy were variably reported by a few studies.The degree of heterogeneity was not improved on exclusion of studies with poor quality, but markedly improved on subgroup analysis according to geographical region and presence of MIS-C. Studies from China showed that children with COVID-19 had significantly lower pooled prevalence for any of the GI symptoms with low degree of heterogeneity, particularly for diarrhea, nausea/vomiting, and abdominal pain, all of which had I2 of 0%. Those with multisystem inflammatory syndrome in children (MIS-C) had significantly more common GI symptoms and increased transaminases than those without.

One-third of children with COVID-19 exhibit at least one GI symptom and more likely present in those with severe disease. Elevated transaminases were present in 10%. Prevalence of GI and hepatic manifestations were higher among children with MIS-C.

The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system's disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.

The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the enzymatic activity of TMPRSS2 in a non-catalytic manner. Furthermore, we demonstrate that ACE2 knockdown inhibits TMPRSS2-mediated cleavage of IAV hemagglutinin (HA) in Calu-3 human airway cells and suppresses virus titers 100- to 1.000-fold. Transient expression of ACE2 in ACE2-deficient cells increased TMPRSS2-mediated HA cleavage and IAV replication. ACE2 knockdown also reduced titers of MERS-CoV and prevented S cleavage by TMPRSS2 in Calu-3 cells. By contrast, proteolytic activation and multicycle replication of IAV with multibasic HA cleavage site typically cleaved by furin were not affected by ACE2 knockdown. Co-immunoprecipitation analysis revealed that ACE2-TMPRSS2 interaction requires the enzymatic activity of TMPRSS2 and the carboxypeptidase domain of ACE2. Together, our data identify ACE2 as a new co-factor or stabilizer of TMPRSS2 activity and as a novel host cell factor involved in proteolytic activation and spread of IAV in human airway cells. Furthermore, our data indicate that ACE2 is involved in the TMPRSS2-catalyzed activation of additional respiratory viruses including MERS-CoV.IMPORTANCEProteolytic cleavage of viral envelope proteins by host cell proteases is essential for the infectivity of many viruses and relevant proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of several respiratory viruses, including influenza A virus. TMPRSS2 was previously shown to interact with angiotensin-converting enzyme 2 (ACE2). Here, we report the mechanistic details of this interaction. We demonstrate that ACE2 increases or stabilizes the enzymatic activity of TMPRSS2. Furthermore, we describe ACE2 involvement in TMPRSS2-catalyzed cleavage of the influenza A virus hemagglutinin and MERS-CoV spike protein in human airway cells. These findings expand our knowledge of the activation of respiratory viruses by TMPRSS2 and the host cell factors involved. In addition, our results could help to elucidate a physiological role for TMPRSS2.