ACE2 Receptor Research Articles

Candida and Long Covid: Mannan Not from Heaven

The pandemic has supercharged growing awareness of the gut microbiome as a critical determinant of human health. “Long haulers” share microbiomes similar to those seen in myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia, all frequently associated with Candida overgrowth (CO). Candida can synthesize its own IDO, altering tryptophan metabolism (ATM). Zonulin, a circulating protein that increases intestinal and endothelial permeability, has emerged as a central player. Candida hyphal walls express proteins analogous to gliadin/gluten, e.g., celiac disease (CeD), and mannans, e.g., Crohn’s disease (CrD), that may trigger antigliadin and anti-Gq coupled GPCR auto-antibodies linked to their lectin binding domain respectively. Hyphal mannan may induce auto-antibodies to AT1Rs, α1-ARs, mAChRs, and β2-ARs, prominent in LC, and regulate T cell receptors (TCRs) and regulatory B cell function, compromised in not only LC (vitiligo, psoriasis, alopecia) but also SLE, RA, and many other autoimmune diseases. All are Gq coupled GPCRs. The spike protein S on SARS CoV2 can attach to both the ACE2 receptor (required for tryptophan absorption) and Toll-like receptor4 (TLR4) bearing endothelial cells and enterocytes. Spike protein S is persistent in most with LC and, as a ligand for TLR4, can also activate zonulin. S can also activate the NLRP3 inflammasome, as can candidalysin. This inflammasome is directly connected to dementia, cancer, autoimmunity and obesity. Candidalysin causes hypercitrullination, instrumental in creating ACPAs (anti-citrullinated peptide antibodies) linked to LC, MCAS (mast cell activation syndrome), HSD (hypermobility spectrum disorder), and APS (antiphospholipid syndrome). A hypothetical pathophysiologic model is proposed implicating pre-existing CO, aggravated by Covid-19, in not only the genesis of LC but also that of autoimmune disease, dementia, cancer, many chronic diseases, and aging.

Identification of South African Plant-Based Bioactive Compounds as Potential Inhibitors against the SARS-CoV-2 Receptor.

The expected progress in SARS-CoV-2 vaccinations, as anticipated in 2020 and 2021, has fallen short, exacerbating global disparities due to a lack of universally recognized "safe and effective" vaccines. This study focuses on extracts of South African medicinal plants, Artemisia annua and Artemisia afra, to identify metabolomic bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors. The extracts were monitored for cytotoxicity using a resazurin cell viability assay and xCELLigence real-time cell analyzer. Chemical profiling was performed using UPLC-MS/MS, orthogonal projection to latent structures (OPLS), and evaluated using principle component analysis (PCA) models. Identified bioactive compounds were subjected to in vitro SARS-CoV-2 enzyme inhibition assay using standard methods and docked into the spike (S) glycoprotein of SARS-CoV-2 using Schrodinger® suite followed by molecular dynamics simulation studies. Cell viability assays revealed non-toxic effects of extracts on HEK293T cells at lower concentrations. Chemical profiling identified 81 bioactive compounds, with compounds like 6″-O-acetylglycitin, 25-hydroxyvitamin D3-26,23-lactone, and sesaminol glucoside showing promising binding affinity. Molecular dynamics simulations suggested less stable binding, but in vitro studies demonstrated the ability of these compounds to interfere with SARS-CoV-2 spike protein's binding to the human ACE2 receptor. Sesaminol glucoside emerged as the most effective inhibitor against this interaction. This study emphasizes the importance of multiplatform metabolite profiling and chemometrics to understand plant extract composition. This finding is of immense significance in terms of unravelling metabolomics bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors and holds promise for phytotherapeutics against SARS-CoV-2.

Peptide S4 is an entry inhibitor of SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant socioeconomic burden, and combating COVID-19 is imperative. Blocking the SARS-CoV-2 RBD–ACE2 interaction is a promising therapeutic approach for viral infections, as SARS-CoV-2 binds to the ACE2 receptors of host cells via the RBD of spike proteins to infiltrate these cells. We used computer-aided drug design technology and cellular experiments to screen for peptide S4 with high affinity and specificity for the human ACE2 receptor through structural analysis of SARS-CoV-2 and ACE2 interactions. Cellular experiments revealed that peptide S4 effectively inhibited SARS-CoV-2 and HCoV-NL63 viruses from infecting host cells and was safe for cells at effective concentrations. Based on these findings, peptide S4 may be a potential pharmaceutical agent for clinical application in the treatment of the ongoing SARS-CoV-2 pandemic.

Impact of mutations in SARS-CoV-2 recombinant sub-variant XBB.1.16 on the binding affinity with human ACE2 receptor

Despite the waning threat of the COVID-19 pandemic, its detrimental impact on global health persists. Regardless of natural immunity or immunity obtained through vaccination, emerging variants of the virus continue to undergo mutations and propagate globally. The persistent mutations in SARS-CoV-2, along with the subsequent formation of recombinant sub-variants has become a challenge for researchers and health professionals, raising concerns about the efficacy of current vaccines. Gaining a better understanding of the biochemical interactions between the Spike Protein (RBD) of SARS-CoV-2 variants and the human ACE2 receptor can prove to be beneficial in designing and developing antiviral therapeutics that are equally effective against all strains and emerging variants. Our objective in this study was to investigate the interfacial binding pattern of the SARS-CoV-2 RBD-ACE2 complex of the Wild Type (WT), Omicron, and the Omicron recombinant sub-variant XBB.1.16. We aimed to examine the atomic level factors and observe how mutations influence the interaction between the virus and its host using Molecular Dynamics simulation, MM/GBSA energy calculations, and Principal Component Analysis. Our findings reveal a higher degree of structural deviation and flexibility in XBB.1.16 compared to WT and Omicron. PCA indicated a wider cluster and significant flexibility in the movements of XBB.1.16 which can also be observed in free energy landscapes, while the normal mode analysis revealed converging motions within the RBD-ACE2 complexes which can facilitate the interaction between them. A pattern of decreased binding affinity was observed in case of XBB.1.16 when compared to the WT and Omicron. These observed deviations in XBB.1.16 when compared to its parent lineage Omicron, and WT can be attributed to the mutations specific to it. Collectively, these results enhance our understanding of the impact of mutations on the interaction between this strain and the host, taking us one step closer to designing effective antiviral therapeutics against the continually mutating strains.

Comparing receptor binding properties of SARS-CoV-2 and of SARS-CoV virus by using unsupervised machine learning models

This work continues our recent molecular dynamics investigation of the three systems of the human ACE2 receptor interacting with the viral RBDs of SARS-CoV virus and two variants of SARS-CoV-2 viruses. The simulations are extended and analyzed using unsupervised machine learning models to give complementary descriptions of hidden features of the viral binding mechanism. Specifically, the principal component analysis (PCA) and the variational autoencoder (VAE) models are employed, both are classified as dimensionality reduction approaches with different focuses. The results support the molecular dynamics results that the two variants of SARS-CoV-2 bind stronger and more stable to the human ACE2 receptor than SARS-CoV virus does. Moreover, stronger bindings also affect the structure of the human receptor, making it fluctuate more, a sensitive feature which is hard to detect using standard analyses. Unexpectedly, it is found that the VAE model can learn and arrange randomly shuffled protein structures obtained from molecular dynamics in time order in the latent space representation. This result potentially has promising application in computational biomolecules. One could use this VAE model to jump forward in time during a molecular dynamics simulation, and to enhance the sampling of protein configuration space.

The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses

Foxes are susceptible to SARS-CoV-2 in laboratory settings, and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes. In this study, we assessed the binding capacities of fox ACE2 to important sarbecoviruses, including SARS-CoV, SARS-CoV-2, and animal-origin SARS-CoV-2 related viruses. Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains (RBDs) of sarbecoviruses. We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV, SARS-CoV-2 prototype (PT), and Omicron BF.7. Through structural analysis, we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2, thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants. In addition, the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-π interaction with K353 in the fox ACE2 receptor. This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD. These results indicate that foxes serve as potential hosts for numerous sarbecoviruses, highlighting the critical importance of surveillance efforts.

Effects of ACE inhibitor/ARB therapy and long COVID on kidney disease: a retrospective cohort study using real-world data.

The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65-0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03-2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00-2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality.

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.

Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2-induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21-encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2-induced neuropathogenesis.

RESEARCH OF MANIFESTATION OF THE ORAL MUCOSA IN COVID-19

The oral cavity is one of the main gates for coronavirus (SARS-CoV-2); the oral cavity also suffers greatly from this infection, because it is one of the most vulnerable places. In addition, since the salivary glands can serve as a reservoir for viruses and support their release into the external environment, it was concluded that saliva, as a component of oral fluid, can play an important role in the spread of coronavirus infection. This is mainly due to the ACE-2 receptor, which have a high level of expression in the keratinized surface epithelial cells of the oral mucosa, especially in the epithelial cells of the dorsal part of the tongue, tonsils, vocal cords, salivary glands and sinuses, due to which the virus replicates in and causes both oral lesions and oral symptoms mouth After entering the cell, the virus delays the response of the immune system, allowing the infection to progress, and it becomes much more difficult to fight it. Accordingly, due to the relatively high level of COVID-19-associated complications, timely diagnosis of clinical forms, including high-risk patients with prognosis their clinical course and the selection of drug treatment appropriate to the severity of the clinical course remain quite complex and controversial issues. It was emphasized that in some cases oral symptoms may be the initial or only sign of disease, and dentists should take this into account when performing a thorough clinical examination of the oral cavity.

Structure-based Virtual Screening from Natural Products as Inhibitors of SARS-CoV-2 Spike Protein and ACE2 Receptor Binding and their Biological Evaluation In vitro.

In the last years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 760 million infections and 6.9 million deaths. Currently, remains a public health problem with limited pharmacological treatments. Among the virus drug targets, the SARS-CoV-2 spike protein attracts the development of new anti-SARS-CoV-2 agents. The aim of this work was to identify new compounds derived from natural products (BIOFACQUIM and Selleckchem databases) as potential inhibitors of the spike receptor binding domain (RBD)-ACE2 binding complex. Molecular docking, molecular dynamics simulations, and ADME-Tox analysis were performed to screen and select the potential inhibitors. ELISA-based enzyme assay was done to confirm our predictive model. Twenty compounds were identified as potential binders of RBD of the spike protein. In vitro assay showed compound B-8 caused 48% inhibition at 50 μM, and their binding pattern exhibited interactions via hydrogen bonds with the key amino acid residues present on the RBD. Compound B-8 can be used as a scaffold to develop new and more efficient antiviral drugs.

The outcome of COVID-19 infection among Saudi oncology patients.

e23085 Background: Little data are available surrounding the outcomes and risk factors of COVID-19 in Saudi oncological patients. This study aims to elucidate the outcomes of COVID-19 infection among Saudi oncology patients and associated risk factors. Methods: We retrospectively reviewed the medical files of oncology patients who were diagnosed with COVID-19 at the King Faisal Specialist Hospital and Research Centre. The time from a positive PCR until death or last follow-up was calculated as COVID-specific survival. A p-value less than 0.05 was selected as the threshold for statistical significance. Results: 161 oncological patients were included in our analysis. The mean age was 53.83±15.81. 85 (52.8%) patients were female, 17 (10.6%) had a positive history of smoking, and 57 (35.4%) were obese. 70 (43.5%) patients had diabetes mellitus, 64 (39.8%) had hypertension, and 25 (15.5%) had dyslipidemia. The most common cancer in the group was breast cancer, which was present in 24 (14.9%), followed by non-Hodgkin lymphoma, colon cancer, and acute leukemia, respectively. 57 (35.4%) patients had no evidence of disease (NED) at presentation. Furthermore, 65 (40.4%) patients had received antineoplastic therapy within 30 days before infection. 25 (15.5%) patients had stage A COVID-19, 59 (36.6%) had stage B, 48 (29.8%) had stage C, and 29 (18%) had stage D. There was no difference between active and no NED patients in remission in regard to the stages of COVID-19 infection at presentation (p = 0.05). However, the stages of COVID were less severe in patients who received antineoplastic therapy (p = 0.02). 32 (19.9%) patients received tocilizumab during the acute phase of infection. Only 5 (3.1%) patients suffered COVID-specific death. Therefore, the median COVID-specific survival was not reached. Tocilizumab (p = 0.34), corticosteroids (p = 0.77), ACE inhibitors (p = 0.45) had no impact on COVID-specific death in our patient population. In patients who received steroid treatment, the duration of corticosteroid had no impact on survival (HR: 0.76, p = 0.39). Ventilation also had no impact on survival (p = 0.55). There was no difference between patients who received antineoplastic therapy within 30 days from infection and those who did not (p = 0.99). Finally, we noted no difference in survival between patients with active disease and NED patients (p = 0.17). Conclusions: COVID-related mortality is lower in Saudi oncology patients compared to other countries. Early management and admission of oncological patients may result in overall improved outcome. In line with some studies, antineoplastic therapy can reduce COVID-19 severity, possibly due to reduced ACE receptor expression.

COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Sequential Infection with Influenza A Virus Followed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Leads to More Severe Disease and Encephalitis in a Mouse Model of COVID-19.

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection ('twinfection') is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19.

Vibration assisted electron tunnelling in COVID-19 infection using quantum state diffusion.

The spread of the COVID-19 virus has become a global health crisis, and finding effective treatments and preventions is a top priority. The field of quantum biology primarily focuses on energy or charge transfer, with a particular emphasis on photosynthesis. However, there is evidence to suggest that cellular receptors such as olfactory or neural receptors may also use vibration-assisted electron tunnelling to enhance their functions. Quantum tunnelling has also been observed in enzyme activity, which is relevant to the invasion of host cells by the SARS-CoV-2 virus. Additionally, COVID-19 appears to disrupt receptors such as olfactory receptors. These findings suggest that quantum effects could provide new insights into the mechanisms of biological systems and disease, including potential treatments for COVID-19. We have applied the open quantum system approach using Quantum State Diffusion to solve the non-linear stochastic Schrödinger equation (SSE) for COVID-19 virus infection. Our model includes the mechanism when the spike protein of the virus binds with an ACE2 receptor is considered as dimer. These two entities form a system and then coupled with the cell membrane, which is modelled as a set of harmonic oscillators (bath). By simulating the SSE, we find that there is vibration-assisted electron tunnelling happening in certain biological parameters and coupling regimes. Furthermore, our model contributes to the ongoing research to understand the fundamental nature of virus dynamics. It proposes that vibration-assisted electron tunneling could be a molecular phenomenon that augments the lock-and-key process for olfaction. This insight may enhance our understanding of the underlying mechanisms governing virus-receptor interactions and could potentially lead to the development of novel therapeutic strategies.

Virus-like structures for combination antigen protein mRNA vaccination

Improved vaccination requires better delivery of antigens and activation of the natural immune response. Here we report a lipid nanoparticle system with the capacity to carry antigens, including mRNA and proteins, which is formed into a virus-like structure by surface decoration with spike proteins, demonstrating application against SARS-CoV-2 variants. The strategy uses S1 protein from Omicron BA.1 on the surface to deliver mRNA of S1 protein from XBB.1. The virus-like particle enables specific augmentation of mRNAs expressed in human respiratory epithelial cells and macrophages via the interaction the surface S1 protein with ACE2 or DC-SIGN receptors. Activation of macrophages and dendritic cells is demonstrated by the same receptor binding. The combination of protein and mRNA increases the antibody response in BALB/c mice compared with mRNA and protein vaccines alone. Our exploration of the mechanism of this robust immunity suggests it might involve cross-presentation to diverse subsets of dendritic cells ranging from activated innate immune signals to adaptive immune signals.

SPIKENET: An Evidence-Based Therapy for Long COVID.

The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.

#2649 Blood pressure tend to decrease following COVID-19 infection in patients with chronic kidney disease—lessons learned from a community based cohort

Abstract Background and Aims Pre-existing hypertension (HTN) has been implicated as one of the most common co-morbidities in COVID-19 patients, likely contributing to disease severity. Additionally, the port of viral entry to the host cell—ACE2 receptor, which is a part of the renin-angiotensin-aldosterone system, was initially thought to cause blood pressure (BP) dysregulation. Recently, several large cohorts have been published, connecting COVID-19 infection to new-onset HTN. Nevertheless, the association of HTN with COVID-19 in patients with chronic kidney disease (CKD) in a community setting has not been fully elucidated. We aimed to study the effect of COVID-19 infection on BP in patients with CKD. Method In this cohort study we utilized the Maccabi Healthcare Services (MHS) database during the COVID-19 pandemic. MHS is a nationwide health care payer-provider, providing health services to approximately 2.6 million Israelis. Data is automatically collected and includes comprehensive laboratory results from a single central lab, full pharmacy prescription and purchase data, physician visits, vital signs documentation, imaging and extensive demographic information on each patient. The database includes several automatically formulated registries including a well validated CKD registry. On July 31st 2023 we looked at point prevalence of patients registered as having CKD stages I-V, defined as eGFR <60 ml/min and/or albuminuria over 30 mg on 24 hour urine collection or 30 mg/g creatinine on urine albumin to creatinine ratio, or proteinuria above 150 mg either at spot urine protein to creatinine ratio or over 24 hour collection. We included CKD patients over the age of 18 years, who had mostly mild COVID-19 disease, detected by SARS-CoV-2 PCR or antigen test between January 1st 2020 and December 31st 2022. Examinees were included only if they had at least one blood pressure measurement documented, in their primary care clinic, in the year prior to infection, and at least one measurement during the 12 months period following COVID-19. Only the 1st documented COVID-19 infection of each patient was included. We compared the differences in BP values between pre and post COVID-19. Results Out of 1,821,685 adults at Maccabi HMS in 2023, 193,566 patients were registered as having CKD. Of those, 86,618 had a documented first COVID-19 infection between the years 2020-2022, and 44,410 of them had documented BP measurements both prior and after COVID-19 were analyzed. Mean age for all CKD patients who had COVID-19 was 69.2 (SD-12.9) years and 22,151 (49.9%) were males. Most patients had CKD stage III—26,939 (60%), and 535 (1.2%) were on dialysis. Not surprisingly, 76% of CKD patients had a preexisting diagnosis of HTN and 44% had diabetes mellitus. Average BP values during the year prior to COVID-19 were 133/76.5 mmHg (SD 14.8 and 8.55, respectively). Mean BP values post COVID-19 were 132/75/9 mmHg (SD 15.5 and 8.9, respectively). This translates into a reduction of 1 mmHg in systolic BP and 0.6 mmHg in diastolic BP in the year prior to COVID-19 infection as compared with pre-covid-19 infection (P-value 0.03 and 0.004, respectively). Conclusion Contrary to previous studies, that linked COVID-19 infection to a higher set-point of BP, our data demonstrates in a large community-based cohort of CKD patients, that BP does not increase and even trends down following COVID-19. As patients were one year older during their post-covid year, and some had withdrew ACE inhibitors or ARB, due to erroneous fear of adverse effect on Covid-19 infectivity, we believe that our results may even underestimate the extent of decrease in BP. Further investigation might reveal the possible mechanisms related to this favorable BP decrease after COVID-19 infection, in CKD patients.

Role Of Acute Vascular Distress Syndrome In The Development Of Multisystem Inflammatory Syndrome In Sars-Cov-2 And Modern Views On The Research And Treatment Of Critical Coronavirus

Background: The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the complex pathology of the virus, which extends beyond respiratory symptoms to include multisystem inflammatory syndrome (MIS). This review explores the role of Acute Vascular Distress Syndrome (AVDS) in the development of MIS in both adults (MIS-A) and children (MIS-C), providing a comprehensive overview of modern research and treatment approaches for severe coronavirus infections. Methods and Materials: This review synthesizes findings from multiple studies and clinical reports to analyze the mechanisms by which SARS-CoV-2 induces AVDS and subsequently MIS. Key materials include molecular and cellular research data, clinical case studies, and treatment protocols. Diagnostic tools such as PCR and serological testing, as well as various biomarkers like neurofilament light chain and galectin-3, are discussed to elucidate their roles in identifying and managing severe COVID-19 cases. Results: The interaction between SARS-CoV-2 and host endothelial cells, mediated by ACE2 receptors, triggers a cascade of inflammatory responses leading to AVDS. This syndrome is characterized by severe endothelial dysfunction, cytokine storms, and mitochondrial distress, which collectively contribute to the pathogenesis of MIS. Clinical evidence indicates that AVDS is a critical factor in the severity of COVID-19, with widespread implications for multiple organ systems, including the central and peripheral nervous systems. Conclusion: Understanding the role of AVDS in MIS development offers valuable insights into the pathophysiology of severe COVID-19. Effective management requires a multifaceted approach, combining antiviral therapies, immunomodulators, and supportive treatments like extracorporeal membrane oxygenation (ECMO). Future research should focus on targeted therapies to mitigate endothelial damage and improve patient outcomes in critical COVID-19 cases.

SARS-CoV-2 omicron BA.2.87.1 exhibits higher susceptibility to serum neutralization than EG.5.1 and JN.1

ABSTRACT As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.

Pituitary and COVID-19 vaccination: a systematic review.

This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland. PubMed and Tripdatabase were searched from January 1st, 2020 to February 12th, 2024. Case reports, case series and reviews related to post COVID-19 vaccination pituitary disease were included. Eligible articles were tabulated and analysed in the attempt to provide an overview on the epidemiology, clinical presentation, imaging, treatment, outcomes and pathophysiological background of post COVID-19 vaccination pituitary disease. Among the 23 case reports included in this review, post COVID-19 vaccination hypophysitis was reported in 9 patients, pituitary apoplexy (PA) in 6 cases, SIADH in 5 cases and Isolated ACTH deficiency in 2 cases. Additionally, precipitating adrenal crisis was registered in 7 patients and pituitary tumor enlargement in 1 patient after receiving COVID-19 vaccination. Despite the rarity of these events, our research findings suggest an association between COVID-19 vaccination and the subsequent development of pituitary diseases. The most common manifestations include hypophysitis with ADH deficiency, PA and SIADH, with symptoms typically emerging shortly after vaccine administration. Potential pathogenetic mechanisms include molecular mimicry, vaccine adjuvants and vaccine-induced thrombotic thrombocytopenia (VITT), with the presence of ACE2 receptors in the hypothalamus-pituitary system contributing to the process. These findings can aid in diagnostic and treatment decisions for patients presenting with these syndromes. Nevertheless, given the rarity of these events, safety and efficacy of the currently available COVID-19 vaccines remain robust and we strongly advocate continuing pursuing vaccination efforts.