Soon after the pandemic outbreak in 2020, it was proposed that binding of SARS-CoV-2 to the angiotensin converting enzyme-2 may explain most of COVID-19's manifestations. Therefore, manipulation of the renin-angiotensin system (RAS) by using well known and commercialized blockers of its classical arm or by repurposing new stimulators of the alternative RAS pathway in clinical development was seen as a potentially effective strategy for the treatment of COVID-19. Moreover, this therapeutic approach had previously shown significant promise in the treatment of other respiratory viral respiratory infections and forms of acute respiratory distress syndrome. Consequently, several randomized clinical trials (RCTs) were launched to test the efficacy of rebalancing the RAS to reduce the severity of COVID-19. While most of these trials produced neutral results, certain studies reached their primary endpoints. In the present collaborative review, sponsors and main investigators of some of these trials attempt to reach a consensus regarding their clinical significance and which factors influenced their differing outcomes. The knowledge gained through the careful analysis of these RCTs of RAS modulators in patients with severe COVID-19 may prove useful for other forms of acute lung injury.

A series of S-adenosyl-L-homosysteine (SAH) analogs, with modification in the base and sugar moiety, have been designed, synthesized and screened as nsp14 and PLpro inhibitors of severe acute respiratory syndrome corona virus (SARS-CoV-2). The outcomes of ADMET (Adsorption, Distribution, Metabolism, Excretion, and Toxicity) studies demonstrated that the physicochemical properties of all analogs were permissible for development of these SAH analogs as antiviral agents. All molecules were screened against different SARS-CoV-2 targets using molecular docking. The docking results revealed that the SAH analogs interacted well in the active site of nsp14 protein having H-bond interactions with the amino acid residues Arg289, Val290, Asn388, Arg400, Phe401 and π-alkyl interactions with Arg289, Val290 and Phe426 of Nsp14-MTase site. These analogs also formed stable H-bonds with Leu163, Asp165, Arg167, Ser246, Gln270, Tyr274 and Asp303 residues of PLpro proteins and found to be quite stable complexes therefore behaved as probable nsp14 and PLpro inhibitors. Interestingly, analog 3 showed significant in silico activity against the nsp14 N7 methyltransferase of SARS-CoV-2. The molecular dynamics (MD) and post-MD results of analog 3 unambiguously established the higher stability of the nsp14 (N7 MTase):3 complex and also indicated its behavior as probable nsp14 inhibitor like the reference sinefungin. The docking and MD simulations studies also suggested that sinefungin did act as SARS-CoV-2 PLpro inhibitor as well. This study's findings not only underscore the efficacy of the designed SAH analogs as potent inhibitors against crucial SARS-CoV-2 proteins but also pinpoint analog 3 as a particularly promising candidate. All the study provides valuable insights, paving the way for potential advancements in antiviral drug development against SARS-CoV-2.

Severe COVID-19 infection has been associated with neurological complications, but its role in accelerating cognitive decline remains unclear.

To determine whether individuals hospitalized for severe COVID-19 exhibit a higher incidence of new onset cognitive impairment compared to those hospitalized for other conditions.

A retrospective study emulating a target trial using Mass General Brigham electronic health records (March 2020-August 2024). The causal effect of COVID-19 hospitalization was estimated via cumulative incidence functions accounting for the competing risk of death.

Multicenter hospital-based study across the Mass General Brigham healthcare system.

A total of 221613 hospitalized patients met the eligibility criteria, including 6454 (2.0%) admitted due to COVID-19 and 215159 (98.0%) for all other conditions. Patients were excluded if they had less than three months of follow-up (due to censoring, cognitive impairment, or death), were younger than 55 years at baseline, or had no prior visit to Mass General Brigham in the year before baseline.

The primary outcome was new-onset cognitive impairment, identified via ICD codes and dementia medication prescriptions. The primary analysis estimated the hazard ratio for cognitive impairment with COVID-19 hospitalization relative to other hospitalizations, along with the risk difference at 4.5 years estimated via cumulative incidence functions. Inverse propensity score weighting was used to balance covariates (age, sex, comorbidities, hospitalization period).

Among eligible patients (mean [SD] age, 69.55 [9.42] years, 55% female), those hospitalized for COVID-19 were significantly older and had more comorbidities (p < 0.05). COVID-19 hospitalization was associated with a higher risk of developing cognitive impairment (Hazard Ratio: 1.14 [95% CI: 1.02-1.30], P = 0.018). At 4.5 years, the cumulative incidence of cognitive impairment was 12.5% [95% CI: 11.3-13.5] in the COVID-19 group, compared to 11.6% [95% CI: 11.1-12.1] in the non-COVID-19 group.

Severe COVID-19 infection was associated with an elevated risk of developing clinically recognized cognitive impairment. Future studies are needed to validate findings in other health care settings. Early screening and intervention for cognitive decline may help optimize long-term outcomes for COVID-19 patients.

N-acetylcysteine (NAC) can take part in the treatment of chronic respiratory diseases because of the potent mucolytic, antioxidant, and anti-inflammatory effects of NAC. However, less is known about its use in the treatment of acute lung injury. Nowadays, an increasing number of studies indicates that early administration of NAC may reduce markers of oxidative stress and alleviate inflammation in animal models of acute lung injury (ALI) and in patients suffering from distinct forms of acute respiratory distress syndrome (ARDS) or pulmonary infections including community-acquired pneumonia or Coronavirus Disease (COVID)-19. Besides low costs, easy accessibility, low toxicity, and rare side effects, NAC can also be combined with other drugs. This article provides a review of knowledge on the mechanisms of inflammation and oxidative stress in various forms of ALI/ARDS and critically discusses experience with the use of NAC in these disorders. For preparing the review, articles published in the English language from the PubMed database were used.

The COVID-19 pandemic has significantly impacted global healthcare systems, revealed vulnerabilities and prompted a re-evaluation of medical practices. Acute complications from the virus, including cardiovascular and neurological issues, have underscored the necessity for timely medical interventions. Advances in diagnostic methods and personalized therapies have been pivotal in mitigating severe outcomes. Additionally, Long COVID has emerged as a complex challenge, affecting various body systems and leading to respiratory, cardiovascular, neurological, psychological, and musculoskeletal problems. This broad spectrum of complications highlights the importance of multidisciplinary management approaches that prioritize therapy, rehabilitation, and patient-centered care. Vulnerable populations such as paediatric patients, pregnant women, and immunocompromised individuals face unique risks and complications, necessitating continuous monitoring and tailored management strategies to reduce morbidity and mortality associated with COVID-19.

The COVID-19 pandemic has left an indelible mark on the world, with mounting evidence suggesting that it not only posed acute challenges to global healthcare systems but has also unveiled a complex array of long-term consequences, particularly cognitive impairment (CI). As the persistence of post-COVID-19 neurological syndrome could evolve into the next public health crisis, it is imperative to gain a better understanding of the intricate pathophysiology of CI in COVID-19 patients and viable treatment strategies.

This comprehensive review explores the pathophysiology and management of cognitive impairment across the phases of COVID-19, from acute infection to Long-COVID, by synthesizing findings from clinical, preclinical, and mechanistic studies to identify key contributors to CI, as well as current therapeutic approaches.

Key mechanisms contributing to CI include persistent neuroinflammation, cerebrovascular complications, direct neuronal injury, activation of the kynurenine pathway, and psychological distress. Both pharmacological interventions, such as anti-inflammatory therapies and agents targeting neuroinflammatory pathways, and non-pharmacological strategies, including cognitive rehabilitation, show promise in addressing these challenges. Although much of the current evidence is derived from preclinical and animal studies, these findings provide foundational insights into potential treatment approaches.

By synthesizing current knowledge, this review highlights the importance of addressing COVID-19-related cognitive impairment and offers actionable insights for mitigation and recovery as the global community continues to grapple with the pandemic's long-term impact.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health, exacerbated metabolic health issues, and altered lifestyle behaviors. This study examined the sex-specific impact of the COVID-19 outbreak on the incidence of metabolic syndrome using data from the Korea National Health and Nutrition Examination Survey (KNHANES).

Data from the KNHANES VII (2018) and VIII (2019-2021), including 15,499 participants, were analyzed. The study population was stratified by sex, and further subdivisions were conducted based on the timeframe relative to the COVID-19 outbreak. Variables such as age, education level, household income, smoking status, and high-risk drinking were analyzed to assess their influence on the prevalence of metabolic syndrome.

The overall prevalence of metabolic syndrome significantly increased from 28.11% before the outbreak to 29.69% after the outbreak. Both males and females reported significant increases in waist circumference and fasting glucose levels. Age and education level differentially influenced the prevalence of metabolic syndrome between the sex. Smoking was significantly associated with increased prevalence in males, whereas high-risk drinking was associated with increased prevalence in males and decreased prevalence in females.

The COVID-19 pandemic has significantly increased the prevalence of metabolic syndrome with notable sex-specific differences. These findings highlight the need for sex-specific public health interventions to mitigate the impact of the pandemic on metabolic health.

Coronavirus disease 2019 (COVID-19) is associated with a wide variety of clinical manifestations.

This study aims to evaluate the levels of angiotensin-converting enzyme 2 (ACE2), metalloprotease 17 (ADAM17), Interleukin-17A (IL-17A), transmembrane serine protease 2 (TMPRSS2), apelin (AP), and vitamin D (VD) biomarkers in nasopharyngeal swab (NPS), serum, and saliva, as well as the change in their values depending on the health status of individuals.

The analysis was performed by using enzyme-linked immunosorbent assay (ELISA) methods.

Comparing the levels of the investigated markers in saliva, we found significantly elevated ACE2 values in vaccinated patients, followed by those with severe COVID-19, compared to healthy, previously infected, and mild COVID-19 groups. For TMPRSS2, IL-17A, ADAM-17, and AP, values were significantly higher in all non-healthy groups (previously infected, mild, and severe COVID-19) compared to healthy individuals. Serum levels of VD were consistently low across all five studied groups, suggesting values below normal ranges. Analysis of marker data in saliva, NPS, and serum revealed a positive correlation between NPS and serum and saliva and serum, as well as between saliva and NPS for all studied markers.

In summary, monitoring changes in biomarkers present in Saliva holds promise as a predictive tool for various diseases. This approach enables the early implementation of preventive measures and protective strategies, potentially improving overall health outcomes.

The 2019 coronavirus illness (COVID 2019) first manifests as a newly identified pneumonia and may quickly escalate to acute respiratory distress syndrome, which has caused a global pandemic. Except for individualized supportive care, no curative therapy has been steadfastly advised for COVID-19 up until this point. T cells and virus-specific T lymphocytes are required to guard against viral infection, particularly COVID-19. Delayed immunological reconstitution (IR) and cytokine storm (CS) continue to be significant barriers to COVID-19 cure. While severe COVID-19 patients who survived the disease had considerable lymphopenia and increased neutrophils, especially in the elderly, their T cell numbers gradually recovered. Exhausted T lymphocytes and elevated levels of pro-inflammatory cytokines, including IL6, IL10, IL2, and IL17, are observed in peripheral blood and the lungs. It implies that while convalescent plasma, IL-6 blocking, mesenchymal stem cells, and corticosteroids might decrease CS, Thymosin α1 and adaptive COVID-19-specific T cells could enhance IR. There is an urgent need for more clinical research in this area throughout the world to open the door to COVID-19 treatment in the future.

Despite the great number of experimental investigations in the area of psycho-neuro-endocrine-immunology showing that endocrine, nervous, and immune systems cannot be in vivo physiologically separated, the diagnosis and therapies of the pathologies of these three functional biological systems continue to be separately performed from a clinical practice point of view. The separation between experimental and clinical medicine became dramatic after the discovery of more than 10 human molecules provided by anti-inflammatory and antitumor activity, completely devoid of any toxicity, which may be subdivided into three fundamental classes, consisting of the pineal indole, beta-carboline, and methoxy-kynuramine hormones. Moreover, human systemic diseases, including cancer, autoimmunity, and cardiovascular pathologies, despite their different pathogenesis and symptomatology, are commonly characterized by a progressive decline in the endogenous production of pineal hormones, endocannabinoids, and Ang 1-7, with a consequent inflammatory status and diminished natural resistance against cancer. Then the evaluation of the functional status of the pineal gland, the endocannabinoid system, and ACE2-Ang 1-7 axis should have to be included within the laboratory analyses for the systemic diseases. Finally, the correction of cancer- and autoimmunity-related neuroimmune and neuroendocrine alterations could influence the clinical course of systemic diseases. In fact, preliminary clinical results would demonstrate that the neuroimmune regimen with pineal hormones, cannabinoids, and Ang 1-7 may allow clinical benefits also in patients affected by systemic pathologies, including cancer, autoimmunity, and cardiovascular diseases, who did not respond to the standard therapies.

Recently, angiotensin-converting enzyme 2 (ACE2) gene has emerged as a potential candidate gene for susceptibility to SARS-CoV-2 infection. We investigated whether ACE2 G8790A (rs2285666) polymorphism could be a genetic marker for susceptibility to COVID-19 and disease severity in Egyptian children and adolescents.

This was a prospective case-control study included 580 cases diagnosed with COVID-19, and 580 matched control children and adolescents. The ACE2 G8790A (rs2285666) polymorphism was genotyped using polymerase chain reaction (PCR) and ACE2 serum level was measured by ELISA.

The ACE2 A/A genotype and A-allele were significantly more represented in cases with COVID-19 as compared to control group (44% vs. 30%; OR = 2.83; [95% CI: 1.27-2.63]; p = 0.006; for the A/A genotype) and (65% vs. 51%; OR = 1.9; [95% CI: 1.06-1.72]; p = 0.01; for the A-allele). The presence of ACE2 G/G genotype was an independent risk factor for severe disease (adjusted OR: 2.08; [95% CI: 1.57-6.78]; p = 0.003).

The ACE2 G8790A (rs2285666) polymorphism may confer susceptibility to COVID-19 in Egyptian children and adolescents. The ACE2 G/G genotype and G-allele was associated with lower ACE2 serum levels and may constitute independent risk factors for disease severity.

Since it first appeared, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had a significant and lasting negative impact on the health and economies of millions of individuals all over the globe. At the level of individual health too, many patients are not recovering fully and experiencing a long-term condition now commonly termed 'long-COVID'. Long-COVID is a collection of symptoms which must last more than 12 weeks following initial COVID infection, and which cannot be adequately explained by alternate diagnoses. The neurological and psychosocial impact of long-COVID is itself now a global health crisis and therefore preventing, diagnosing, and managing these patients is of paramount importance. This review focuses primarily on: neurological functioning deficits; mental health impacts; long-term mood problems; and associated psychosocial issues, among patients suffering from long-COVID with an eye towards the neurological basis of these symptoms. A concise account of the clinical relevance of the neurological and psychosocial impacts of long-COVID, the effects on long-term morbidity, and varied approaches in managing patients with significant chronic neurological symptoms and conditions was extracted from the literature, analysed and reported. A comprehensive account of plausible pathophysiological mechanisms involved in the development of long-COVID, its management, and future research needs have been discussed.

COVID-19 infection and vaccination have been reported to confer an elevated risk for cardiovascular events (CVE). We sought to determine whether individuals with an underlying vascular connective tissue disorder including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), or vascular Ehlers Danlos syndrome (vEDS) are at increased risk for cardiac events after COVID-19 infection or vaccination.

325 respondents self-reported data through a cross-sectional, web-based survey available from 22 November 2021, through 15 March 2022 regarding COVID-19 illness and vaccinations, the occurrence of any CVE, and adverse events following vaccination. The data were analyzed using a Cox proportional hazards model with time varying indicators for COVID-19 illness/vaccination in the preceding 30 days.

COVID-19 illness was significantly associated with an increased rate of a new abnormal heart rhythm 30 days following infection. No other CVEs were reported in the 90 days after COVID-19 illness. We did not find evidence of an increased rate of any CVE in the 30 days following any COVID-19 vaccination dose.

In respondents with MFS, LDS, or vEDS, we uncovered no evidence of an increase in CVEs in the 30 days following COVID-19 illness, with the possible exception of dysrhythmia. In light of the absence of a substantial increase in self-reported CVEs in the 30 days following COVID-19 vaccination, these data are in keeping with the recommendation from the Marfan Foundation Professional Advisory Board that all eligible persons be vaccinated for COVID-19.

COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) had an adverse effect globally because it caused a global pandemic with several million deaths. This virus possesses spike protein that is cleaved or activated by Furin-like protease enzymes occurring by mammalian lung or respiratory cells to enter the mammalian body. The addition of the Furin cleavage site in SARS-CoV-2 makes it a more infectious and emerging virus than its ancestor's viruses. Phylogenetic relationships of coronavirus spike proteins have analyzed and mapped Furin recognition motif on the tree using bioinformatics tools such as GTEx, KEGG, GO, NCBI, PolyPhen-2, SNAP2, PANTHER, Hidden Markov Models (Fathmm), Phd-single-nucleotide polymorphism (SNP), I-TASSER, Modpred, Phobius, SIFT, iPTREE-STAB, and PROVEAN. During this study, it has been found that in certain regions, Furin SNPs have some relation with the susceptibility to SARS-CoV-2. Whereas in other regions, the effects are very negligible. Finally, our study demonstrates that Furin SNPs have a strong relationship with susceptibility to SARS-CoV-2. As it helps to cleave the spike protein of the virus, thus it can be targeted to inhibit at a particular site to prevent the SARS-CoV-2 from the entrance into the body.

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.

The angiotensin-converting enzyme 2 (ACE2) and its homolog, the angiotensin converting enzyme 1 (ACE), are involved in COVID-19 physiopathology. Alterations in the enzymatic structure, expression, and/or activity may influence the risk of infection and severity of disease. For this reason, we aimed to identify different allelic forms of ACE2 G8790A and ACE I/D polymorphisms in a Brazilian cohort and evaluate their impact on ACE and ACE2 activities and their association with COVID-19 susceptibility and severity.

A total of 549 COVID-19-negative and 270 COVID-19-positive participants from Ipaussu, Sao Paulo, Brazil, were recruited. ACE2 and ACE activities were measured by fluorogenic assays using MCA-Ala-Pro-Lys(Dnp) as the substrate for ACE2 and Z-Phe-His-Leu-OH (Z-FHL) and Hippuryl-His-Leu-OH (h-HL) as substrates for ACE. Genomic DNA was extracted from EDTA-peripheral blood, and the regions of the genes containing ACE2 G8790A and ACE I/D polymorphisms were amplified by PCR-restriction fragment length polymorphism and real-time PCR, respectively.

The G allele of ACE2 G8790A polymorphism and D allele of ACE I/D polymorphism are associated with increased ACE and ACE2 activities. ACE activity ratio (Z-FHL/h-HL), an inflammatory marker, is increased in women with GG genotype and COVID-19-positive diagnosis.

For the first time, it was demonstrated that in females, the GG genotype is associated with increased ACE activity ratio (Z-FHL/h-HL) in the COVID-19-positive group. Elevated ACE activity ratio (Z-FHL/h-HL) is highly linked to inflammation and may justify the associations between the G genotype and COVID-19 severity of symptoms and outcomes.

The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation.

Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed.

In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]).

UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.

There is increasing evidence that COVID-19 induces endothelial dysfunction that may precede thrombotic and cardiovascular complications. The aim of this study is to evaluate endothelial function using peripheral arterial tonometry (EndoPAT). The primary endpoint is the hyperemic vascular response index (LnRHI) at two months post-discharge. Secondary endpoints include the LnRHI during hospitalization and at six-month follow-up, the proportion of patients with endothelial dysfunction (LnRHI ≤ 0.51), and the incidence of thrombotic events, cardiovascular complications, and mortality during the follow-up period. The study included 23 COVID-19 patients and 22 COVID-19-negative, matched controls. The patients exhibited a significant reduction in the LnRHI at two months post-discharge compared to the controls (median = 0.55 [IQR: 0.49-0.68] vs. median = 0.70 [IQR: 0.62-0.83]; p = 0.012). The difference in the LnRHI between patients and controls was evident from hospitalization and persisted at two and six months without significant temporal changes. The proportion of COVID-19 patients with endothelial dysfunction (LnRHI ≤ 0.51) was 61% during hospitalization and 55% at six months. There was no significant difference in thrombotic or cardiovascular events, nor in mortality. This study demonstrates that COVID-19 adversely affects endothelial function, as evidenced by a reduction in the hyperemic vascular response index, and endothelial dysfunction may also persist.

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.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) preferentially infects the respiratory tract; however, several studies have implicated a multi-organ involvement. Hepatic dysfunctions caused by SARS-CoV-2 infection have been increasingly recognized and described to correlate with disease severity. To elucidate molecular factors that could contribute towards hepatic infection, we concentrated on microRNAs (miRNAs), a class of small non-coding RNAs that modulate various cellular processes and which are reported to be differentially regulated during liver injury. We aimed to study the infection of primary human hepatocytes (PHH) with SARS-CoV-2 and to evaluate the potential of miRNAs for modulating viral infection.

We analysed liver autopsies from a coronavirus disease 19 (COVID-19)-positive cohort for the presence of viral RNA using Nanopore sequencing. PHH were used for the infection with SARS-CoV-2. The candidate miRNAs targeting angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) were identified using in silico approaches. To discover the potential regulatory mechanism, transfection experiments, qRT-PCRs, western blots and luciferase reporter assays were performed.

We could detect SARS-CoV-2 RNA in COVID-19-positive liver autopsies. We show that PHH express ACE2 and TMPRSS2 and can be readily infected with SARS-CoV-2, resulting in robust replication. Transfection of selected miRNA mimics reduced SARS-CoV-2 receptor expression and SARS-CoV-2 burden in PHH. In silico and biochemical analyses supported a potential direct binding of miR-141-3p to the SARS-CoV-2 genome.

We confirm that PHH are susceptible to SARS-CoV-2 infection and demonstrate selected miRNAs targeting SARS-CoV-2 entry factors and/or the viral genome reduce viral loads. These data provide novel insights into hepatic susceptibility to SARS-CoV-2 and associated dysfunctions in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells, via its spike protein, and transmembrane protease, serine 2 (TMPRSS2) cleaves the spike-ACE2 complex to facilitate virus entry. As rate-limiting steps for virus entry, modulation of ACE2 and/or TMPRSS2 may decrease SARS-CoV-2 infectivity and COVID-19 severity. In silico modeling suggested the natural bioactive flavonoid quercetin can bind to ACE2 and a recent randomized clinical trial demonstrated that oral supplementation with quercetin increased COVID-19 recovery. A range of cultured human cells were assessed for co-expression of ACE2 and TMPRSS2. Immortalized Calu-3 lung cells, cultured and matured at an air-liquid interface (Calu-3-ALIs), were established as the most appropriate. Primary bronchial epithelial cells (PBECs) were obtained from healthy adult males (N = 6) and cultured under submerged conditions to corroborate the outcomes. Upon maturation or reaching 80% confluence, respectively, the Calu-3-ALIs and PBECs were treated with quercetin, and mRNA and protein expression were assessed by droplet digital PCR and ELISA, respectively. SARS-CoV-2 infectivity, and the effects of pre- and co-treatment with quercetin, was assessed by median tissue culture infectious dose assay. Quercetin dose-dependently decreased ACE2 and TMPRSS2 mRNA and protein in both Calu-3-ALIs and PBECs after 4 h, while TMPRSS2 remained suppressed in response to prolonged treatment with lower doses (twice daily for 3 days). Quercetin also acutely decreased ADAM17 mRNA, but not ACE, in Calu-3-ALIs, and this warrants further investigation. Calu-3-ALIs, but not PBECs, were successfully infected with SARS-CoV-2; however, quercetin had no antiviral effect, neither directly nor indirectly through downregulation of ACE2 and TMPRSS2. Calu-3-ALIs were reaffirmed to be an optimal cell model for research into the regulation of ACE2 and TMPRSS2, without the need for prior genetic modification, and will prove valuable in future coronavirus and respiratory infectious disease work. However, our data demonstrate that a significant decrease in the expression of ACE2 and TMPRSS2 by a promising prophylactic candidate may not translate to infection prevention.

The coronavirus disease 2019 (COVID-19) reportedly exacerbates cancer outcomes. However, how COVID-19 influences cancer prognosis and development remains poorly understood. Here, we investigated the effect of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), the etiological agent of COVID-19, on cellular cancer phenotypes the expression of cancer-related markers, and various proinflammatory cytokines. We infected prostate (22RV1) and colorectal (DLD-1) cancer cell lines, which express angiotensin-converting enzyme 2 (ACE2), with spike pseudovirus (sPV) and laboratory stocks of live SARS-CoV-2 viruses. After infection, we quantified changes in the cellular cancer phenotypes, the gene expression levels of some cancer markers, including Ki-67, BCL-2, VIM, MMP9, and VEGF, and proinflammatory cytokines. Phenotypic analysis was performed using MTT and wound healing assays, whereas gene expression analysis was carried out using real-time quantitative PCR (RT-qPCR). We show that SARS-CoV-2 infection impacts several key cellular pathways involved in cell growth, apoptosis, and migration, in prostate and colorectal cancer cells. Our results suggest that SARS-CoV-2 infection does influence various cancer cellular phenotypes and expression of molecular cancer markers and proinflammatory cytokines, albeit in a cell-type-specific manner. Our findings hint at the need for further studies and could have implications for evaluating the impact of other viruses on cancer progression.

Background: Methionine (Met) is a popular nutritional supplement in humans and animals. It is routinely supplemented to pigs as L-Met, DL-Met, or DL-2-hydroxy-4-(methylthio) butanoic acid (DL-HMTBA). Methods: We investigated the effect of these Met supplements on jejunal amino acid (AA) transport in male castrated Piétrain × Danbred pigs, also including a non-supplemented group. The mucosal-to-serosal flux of ten [14C]-labeled AAs (L-glutamine, glycine, L-leucine, L-lysine, L-Met, L-serine, L-threonine, L-tryptophan, L-tyrosine and L-valine) was investigated at two concentrations (50 µM and 5 mM). Inhibition of apical uptake by mucosal L-Met was also measured for these AAs. The intestinal expression of apical AA transporters, angiotensin-converting enzyme II and inflammation-related genes were compared with those of a previous study. Results: Except for tryptophan and lysine at 5 mM, all AA fluxes were Na+-dependent (p ≤ 0.05), and the uptake of most AAs, except glycine and lysine, was inhibited by L-Met (p < 0.001). A correlation network existed between Na+-dependent fluxes of most AAs (except tryptophan and partly glycine). We observed the upregulation of B0AT1 (SLC6A19) (p < 0.001), the downregulation of ATB0,+ (SLC6A14) (p < 0.001) and a lower expression of CASP1, IL1β, IL8, TGFβ and TNFα in the present vs. the previous study (p < 0.001). Conclusions: The correlating AAs likely share the same Na+-dependent transporter(s). A varying effect of the Met supplement type on AA transport in the two studies might be related to a different level of supplementation or a different inflammatory status of the small intestine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spread rapidly from China around the world, causing the worst pandemic since the beginning of the 21st century. Although the disease named coronavirus disease 2019 (COVID-19) has multiple organ symptoms, the main pathological lesions occur in the lung, causing respiratory failure, pulmonary embolism, secondary bacterial pneumonia and pulmonary fibrosis. Despite the best efforts of researchers, the pathogenesis of SARS-CoV-2-induced cellular and tissue damage in organs and systems is poorly understood. Therefore, in our study, we aimed to highlight the pulmonary lesions and their extent, which could explain the complex symptomatology presented by patients who died with acute respiratory distress syndrome (ARDS). The study was performed on a number of 36 patients diagnosed with COVID-19 who died under legally suspicious conditions, requiring autopsy within the Romanian Forensic Medicine Institutes. All patients presented a local inflammatory reaction of pneumonic type, with exudative and proliferative phenomena, with intra-alveolar and interstitial inflammatory infiltrates formed by lymphocytes, macrophages and neutrophilic granulocytes, with congested or ruptured blood vessels with intra-alveolar or interstitial hemorrhages, with multiple thrombosis, with proliferation of local fibroblasts transformed into myofibroblasts and presence of granulation tissue that remodeled the entire lung parenchyma.

The COVID-19 outbreak has garnered significant global attention due to its impact on human health. Despite its relatively low fatality rate, the virus affects multiple organ systems, resulting in various symptoms such as palpitations, headaches, muscle pain, and hearing loss among COVID-19 patients and those recovering from the disease. These symptoms impose a substantial physical, psychological, and social burden on affected individuals. On February 15, 2020, the Chinese government advised incorporating antimalarial drugs into the guidelines issued by the National Health Commission of China for preventing, diagnosing, and treating COVID-19 pneumonia. We examine the adverse effects of Chloroquine (CQ) in treating COVID-19 complications to understand why it is no longer the primary treatment for the disease.

Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility.

This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones.

Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted.

The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio.

The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways.

Evidence has shown increased morbidity and mortality for patients with COVID-19 infection within 7 weeks of surgery. However, no studies have specifically investigated the effects of COVID-19 in microsurgical outcomes. This study evaluated thrombotic and overall complications after free tissue transfer for a variety of indications in patients with and without previous COVID-19 infection.

A retrospective cohort study was performed in adult patients with or without a history of COVID-19 infection who underwent microsurgical reconstruction between 2017 and 2022. Patients with a history of COVID-19 infection were matched to controls based on age, gender, race, body mass index, history of diabetes, coronary artery disease, hypertension, Caprini score, tobacco use, and flap indication.

From 2017 to 2022, 35 patients had a documented history of COVID-19. Matched case analysis determined a 4.8 times increased odds ratio of postoperative complications in the COVID-19 group compared with controls (p = 0.002). Significantly, more patients with COVID-19 experienced total or partial flap loss and anastomotic issues (COVID-19: 7/35, Control: 0/35; p < 0.001). There was no significant difference in incidence of VTE (COVID-19: 1/35, Control: 0/35; p = 0.493). Of note, 62.9% of the COVID-19 group were discharged on anticoagulants (versus 14.3% in the control group [p < 0.001]).

COVID-19 has dire, long-lasting effects on virtually every organ system, chief among them, the microcirculation. Further studies are needed to fully determine the extent and influence of COVID-19 on complex procedures such as free tissue transfer and how to optimize the screening, workup, and postoperative care to guard against the associated thrombotic consequences.

Autoantibodies are immune system-produced antibodies that wrongly target the body's cells and tissues for attack. The COVID-19 pandemic has made it possible to link autoantibodies to both the severity of pathogenic infection and the emergence of several autoimmune diseases after recovery from the infection. An overview of autoimmune disorders and the function of autoantibodies in COVID-19 and other infectious diseases are discussed in this review article. We also investigated the different categories of autoantibodies found in COVID-19 and other infectious diseases including the potential pathways by which they contribute to the severity of the illness. Additionally, it also highlights the probable connection between vaccine-induced autoantibodies and their adverse outcomes. The review also discusses the therapeutic perspectives of autoantibodies. This paper advances our knowledge about the intricate interaction between autoantibodies and COVID-19 by thoroughly assessing the most recent findings.

Our study aimed to describe the group of severe COVID-19 patients at an institutional level, and determine factors associated with different outcomes.

A retrospective chart review of patients admitted with severe acute hypoxic respiratory failure due to COVID-19 infection. Based on outcomes, we categorized 3 groups of severe COVID-19: (1) Favorable outcome: progressive care unit admission and discharge (2) Intermediate outcome: ICU care (3) Poor outcome: in-hospital mortality.

Eighty-nine patients met our inclusion criteria; 42.7% were female. The average age was 59.7 (standard deviation (SD):13.7). Most of the population were Caucasian (95.5%) and non-Hispanic (91.0%). Age, sex, race, and ethnicity were similar between outcome groups. Medicare and Medicaid patients accounted for 62.9%. The average BMI was 33.5 (SD:8.2). Moderate comorbidity was observed, with an average Charlson Comorbidity index (CCI) of 3.8 (SD:2.6). There were no differences in the average CCI between groups(p = 0.291). Many patients (67.4%) had hypertension, diabetes (42.7%) and chronic lung disease (32.6%). A statistical difference was found when chronic lung disease was evaluated; p = 0.002. The prevalence of chronic lung disease was 19.6%, 27.8%, and 40% in the favorable, intermediate, and poor outcome groups, respectively. Smoking history was associated with poor outcomes (p = 0.04). Only 7.9% were fully vaccinated. Almost half (46.1%) were intubated and mechanically ventilated. Patients spent an average of 12.1 days ventilated (SD:8.5), with an average of 6.0 days from admission to ventilation (SD:5.1). The intermediate group had a shorter average interval from admission to ventilator (77.2 hours, SD:67.6), than the poor group (212.8 hours, SD:126.8); (p = 0.001). The presence of bacterial pneumonia was greatest in the intermediate group (72.2%), compared to the favorable group (17.4%), and the poor group (56%); this was significant (p<0.0001). In-hospital mortality was seen in 28.1%.

Most patients were male, obese, had moderate-level comorbidity, a history of tobacco abuse, and government-funded insurance. Nearly 50% required mechanical ventilation, and about 28% died during hospitalization. Bacterial pneumonia was most prevalent in intubated groups. Patients who were intubated with a good outcome were intubated earlier during their hospital course, with an average difference of 135.6 hours. A history of cigarette smoking and chronic lung disease were associated with poor outcomes.

The COVID-19 pandemic has revealed a bidirectional relationship between SARS-CoV-2 infection and diabetes mellitus. Existing evidence strongly suggests hyperglycemia as an independent risk factor for severe COVID-19, resulting in increased morbidity and mortality. Conversely, recent studies have reported new-onset diabetes following SARS-CoV-2 infection, hinting at a potential direct viral attack on pancreatic beta cells. In this review, we explore how hyperglycemia, a hallmark of diabetes, might influence SARS-CoV-2 entry and accessory proteins in pancreatic β-cells. We examine how the virus may enter and manipulate such cells, focusing on the role of the spike protein and its interaction with host receptors. Additionally, we analyze potential effects on endosomal processing and accessory proteins involved in viral infection. Our analysis suggests a complex interplay between hyperglycemia and SARS-CoV-2 in pancreatic β-cells. Understanding these mechanisms may help unlock urgent therapeutic strategies to mitigate the detrimental effects of COVID-19 in diabetic patients and unveil if the virus itself can trigger diabetes onset.

To examine the long-term effects of COVID-19 on surgical nurses.

Individuals contaminated with COVID-19 may face several metabolic or psychological issues, primarily in the respiratory, cardiovascular, nervous, musculoskeletal and renal systems during the late period. However, the long-term epidemiology is still not clear.

Descriptive cross-sectional study.

The study included nurses (n = 509) who had been diagnosed with COVID-19 at least 12 weeks before and worked in surgical departments. We collected the study data via an online survey using the snowball sampling method between December 2021 and May 2022. This study followed the Reporting of Observational Studies in Epidemiology Guideline.

The mean age of the nurses was 31.66 ± 8.74 years. Nurses stated that they were diagnosed with COVID-19 approximately 36 weeks before participating in this study. We found that the nurses mostly experienced palpitation (83.5%), headache (73.5%), dyspnea (64.1%), anosmia (57.6%), arthralgia (55.7%) and burnout (58.4%) during the late period after COVID-19.

The long-term effects of COVID-19 were related to multiple organ dysfunctions.

Since the study was conducted with healthy individuals who had previously experienced COVID-19, there is no patient contribution.

This study focuses on the long-term effects of COVID-19 on nurses. The results support the long-term effects of COVID-19 and are thought to contribute to the literature.

Rho kinase (ROCK) pathway plays a critical role in post-COVID-19 pulmonary fibrosis (PCPF) and its intervention with angiotensin-converting enzyme 2 (ACE2) and vascular endothelial growth factor (VEGF) will be a potential therapeutic target.

The present study was conducted to investigate the efficacy of zoledronate (ZA) on carbon tetrachloride (CCl4) induced pulmonary fibrosis (PF) in rats through targeting ACE2, ROCK, and VEGF signaling pathways.

Fifty male Wistar rats were divided into five groups: control, vehicle-treated, PF, PF-ZA 50, and PF-ZA 100 groups. ZA was given in two different doses 100 and 50 μg/kg/week intraperitoneally. After anesthesia, mean arterial blood pressure (MBP) was measured. After scarification, lung coefficient was calculated. Lung levels of ACE 2, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), VEGF, glutathione (GSH), and superoxide dismutase (SOD) were measured. Expression of ROCK, phosphorylated myosin phosphatase target subunit 1 (P-MYPT1), and matrix metalloproteinase (MMP-1), along with histopathological changes and immune-histochemical staining for lung α-smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNFα), and caspase-3, were evaluated.

ZA significantly prevented the decrease in MBP. ZA significantly increased ACE2, GSH, and SOD and significantly decreased IL-1β, TGF-β, and VEGF in lung in comparison to PF group. ZA prevented the histopathological changes induced by CCl4. ZA inhibited lung expression of ROCK, P-MYPT1, MMP-1, α-SMA, TNFα, and caspase-3 with significant differences favoring the high dose intervention.

ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.

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.