Serum angiotensin-converting enzyme 2 as a potential biomarker for SARS-CoV-2 infection and vaccine efficacy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 12, 2022

Various species of the SARS-CoV-2 host cell receptor, angiotensin-converting enzyme 2 (ACE2), are present in serum, which may result from virus entry and subsequent proteolytic processing membrane receptor. We have recently demonstrated changes particular ACE2 infected humans, either cleaved fragments or circulating full-length species. Here, we further explore potential serum as a biomarker to test infection vaccine efficacy susceptible transgenic K18-hACE2 mice expressing human ACE2. First, samples derived challenged with lethal dose SARS-CoV-2, observed an increase levels fragment at day post-challenge, represent through entry. These elevated were maintained until death animals 6 post-challenge. The form displayed sizable peak 4, declined Noticeably, immunization two doses MVA-CoV2-S candidate prevented SARS-CoV-2. was extended vaccinated after re-challenge. findings highlight that could be for disease progression vaccination against

Language: Английский

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Mechanism Underlying the Immune Responses of a Sublingual Vaccine for SARS-CoV-2 with RBD Antigen and Adjuvant, Poly(I:C) or AddaS03, in Non-human Primates

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 16, 2023

Abstract A sublingual vaccine formulated with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and Poly(I:C)) adjuvant was assessed for its safety in non-human primates. This Poly(I:C)-adjuvanted safe compared to the AddaS03-adjuvanted blood tests plasma CRP. The of also confirmed through quantitative reverse transcription PCR six genes ELISA four cytokines associated inflammation related reactions. Poly(I:C)- or produced RBD-specific IgA antibodies nasal washings, saliva, plasma. neutralizing were detected plasma, suggesting that adjuvanted-sublingual vaccines protect against infection. “Yin Yang”-like unique transcriptional regulation observed DNA microarray analyses white cell RNAs from both vaccines, suppressing enhancing immune responses up- downregulating these responses. Poly(I:C) adjuvanted vaccination induced atypical downregulation suppression tolerance; Treg differentiation; T-cell exhaustion. Therefore, is favorable can induce a balanced “Yin/Yang” -like effect on

Language: Английский

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The Serum ACE2, CTSL, AngII, and TNFα Levels after COVID-19 and mRNA Vaccines: The Molecular Basis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(12), P. 3160 - 3160

Published: Nov. 27, 2023

The SARS-CoV-2 virus as well the COVID-19 mRNA vaccines cause an increased production of proinflammatory cytokines.We investigated relationship between ACE2, CTSL, AngII, TNFα and serum levels IL-6, IL-10, IL-33, IL-28A, CD40L, total IgM, IgG, IgA absolute count T- B-lymphocytes in patients, vaccinees healthy individuals.We measured humoral biomarkers (CD40L, IL-33) by ELISA method. Immunophenotyping lymphocyte subpopulations was performed flow cytometry. Total immunoglobulins were analyzed turbidimetry method.The results established increase for AngII severely ill patients vaccinated persons. correlation analysis described a positive ACE2 cytokines IL-33 (r = 0.539) CD40L 0.520), 0.504), 0.416), 0.437) IL-28A 0.592). Correlation confirmed only two relationships 0.491) 0.458).In summary, findings presented this study unveil complex web interactions within immune system response to infection vaccination.

Language: Английский

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ACE2 Receptor: A Potential Pharmacological Target in COVID-19

Current Protein and Peptide Science, Journal Year: 2023, Volume and Issue: 24(9), P. 701 - 710

Published: Aug. 17, 2023

Studies have shown that injection of recombinant angiotensin-converting enzyme 2 (ACE2) significantly increased circulatory levels ACE2 activity, reduced cardiac hypertrophy and fibrosis, effectively lowered blood pressure. In addition, ameliorated albuminuria might contribute to renal protection. Meanwhile, potential pharmacological treatments based on are attracting increasing attention from scientists following a growing understanding the role receptor in pathogenesis coronavirus disease 2019 (COVID-19). this article, we comprehensively summarized literature structure, distribution, function ACE2. More importantly, draw conclusion decoys such as sACE2, hrsACE2 ACE2-derived peptides, drugs down-regulating or TMPRSS2 gene expression, application epigenetic modifiers Traditional Chinese Medicine represent promising approaches for future COVID-19 treatment.

Language: Английский

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Extracellular vesicles and angiotensin-converting enzyme 2 in COVID-19 disease

Biocell, Journal Year: 2024, Volume and Issue: 48(1), P. 1 - 8

Published: Jan. 1, 2024

Extracellular vesicles (EVs) are membranous vesicular structures released from almost all eukaryotic cell types under different physiological or pathological conditions. Growing evidence demonstrates that EVs can serve as mediators of intercellular communication between donor and recipient cells microorganism-infected noninfected cells. Coronavirus disease 2019 (COVID-19) is caused by infection the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host in system various extra-pulmonary tissue/organs, resulting complications multiple organ systems. As surface receptor, angiotensin-converting enzyme (ACE2) mediates cellular entry SARS-CoV-2 into patients with COVID-19. Recent studies have found ACE2 be EVs, which been shown to interfere virus thus may involved COVID-19 pathophysiology. In addition, ACE2, neprilysin (NEP), thimet oligopeptidase (TOP) key enzymes regulate angiotensin metabolism converting II I 1-7, latter has protective effects counterbalancing harmful disease. This review summarizes recent research progress regarding EV-associated NEP, TOP perspectives their potential involvement pathophysiology

Language: Английский

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Reduced Salivary Gustin and Statherin in Long-COVID Cohort with Impaired Bitter Taste

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(22), P. 6816 - 6816

Published: Nov. 13, 2024

Background/Objectives: Taste dysfunction is a frequent symptom of acute coronavirus disease (COVID)-19 caused by the severe respiratory syndrome coronavirus-2 (SARS-CoV-2). While majority those affected reported recovery over time, emerging data suggest that 20–25% individuals experience persistent taste dysfunction, constituting common long COVID. Gustation mediated continuously renewing bud cells. A balance between counteracting processes cell generation and death maintains homeostatic turnover. Sonic hedgehog (SHH) morphogenic protein promotes proliferation differentiation. Enzymatic proteins such as gustin modulate environment around receptors influence perception. Hence, we hypothesized increased turnover reduced taste-related salivary contribute to in Methods: Unstimulated whole saliva (UWS) was collected from with COVID experiencing after obtaining informed consent. The normal control included archived samples catalogued prior 2019. perception objectively determined waterless empirical test. SHH, gustin, inflammatory cytokines UWS were ELISA. expressions epithelial taste-cell-specific markers cellular assessed immunoflurorescence. Results: Impaired bitter most long-COVID cohort. Salivary significantly lower correlated score. Cellular showed keratin-10- small-proline-rich protein-positive cells well SHH-, occluding- KCNQ1-positive Conclusions: could be marker for impaired

Language: Английский

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Circulating angiotensin converting enzyme 2 and COVID-19

World Journal of Clinical Cases, Journal Year: 2022, Volume and Issue: 10(34), P. 12470 - 12483

Published: Dec. 1, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. SARS-CoV-2 infection-related illness been dubbed the disease 2019 (COVID-19) by World Health Organization. Asymptomatic and subclinical infections, hyper-inflammatory state, mortality are all examples of clinical signs. After attaching to angiotensin converting enzyme (ACE2) receptor, virus can enter cells through membrane fusion endocytosis. In addition enabling viruses cling target cells, connection between spike protein (S-protein) ACE2 may potentially impair functionality ACE2. Blood pressure is controlled ACE2, which catalyzes hydrolysis active vasoconstrictor octapeptide (Ang) II heptapeptide Ang-(1-7) free L-Phe. Additionally, Ang I be broken down into Ang-(1-9) metabolized Ang-(1-7). Numerous studies have demonstrated that circulating (cACE2) ability restore myocardial damage in variety cardiovascular diseases anti-inflammatory, antioxidant, anti-apoptotic, anti-cardiomyocyte fibrosis actions. There some suggestions for raising expression COVID-19 patients, might used as creation novel treatment therapies. With regard this, neutralized soluble recombinant human (hrsACE2), binds viral S-protein reduces organs, including heart, kidneys, lungs, lowering concentrations enhancing conversion This review aims investigate how presence cACE2 related. there will discussion number potential therapeutic approaches tip ACE/ACE-2 balance favor ACE-2/Ang-(1-7) axis.

Language: Английский

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S protein, ACE2 and Host Cell Proteases in SARS-CoV2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword?

Published: Dec. 2, 2022

Since the spread of deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how factually enters host cells. Some proteins on each side interaction between and cells are involved as major contributors to this process: 1- nano-machine Spike protein behalf virus, 2- angiotensin converting enzyme II, mono-carboxypeptidase key component renin system cell, 3- some proteases exploited by SARS-CoV2, In review, complex process entrance into with contribution well sequential conformational changes tending increase probability complexification latter receptor cells, discussed. Besides, release catalytic ectodomain II its soluble form extracellular space positive or negative impact infectivity considered.

Language: Английский

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The Emerging Role of Photobiomodulation in COVID-19 Therapy – Part I

Medical Research Archives, Journal Year: 2023, Volume and Issue: 11(8)

Published: Jan. 1, 2023

Background. Infectivity, genomic variability, and symptomatic diversity of the SARS-CoV-2 virus represents a persistent challenge in treatment acute long COVID-19 diseases. A direct consequence pervasive ACE-2 receptors susceptible to virion’s spike protein, disease trajectories commence as upper respiratory infection migrating into bronchia (presenting coughing, dyspnea, fever), followed by viremic circulatory distress from inflammation visceral epithelium vascular endothelia, decreased blood perfusion, hypoxia. Severe cases include hyperinflammation, cytokine storms, multisystem inflammatory syndrome with lung nerve damage, chronic cognitive deficits. Method. This paper (Part I) considers requirements for treating deep-tissue photobiomodulation (PBM) sinuses, lungs other populated organs using transdermal transcranial light primary therapeutic modality. Analysis. detailed analysis optics, biophysics, numerical simulations, quantum photochemistry non-invasive deep tissue PBM infected was performed including optical design, photonic control, irradiance, fluence, modulation, protocols. Results. Analysis concludes large-area 3D bendable LED pads are best suited transdermally treat whole-organ lungs, abdominal cavity (and transcranially long-COVID). Robotic laser scanning another viable option provided angle incidence is minimal. Penetration depth depends on wavelength (not power) red (635nm) NIR (850nm) shown adequately penetrate through cutaneious parietal fascia viscera. Conclusions. Red LEDs average pulsed irradiances 8.5 13.5 mW/cm2 respectively deliver hands-free doses between 0.5 4.0 J/cm2 60 min sessions surface dose Pl/A = 40 depending transmission coefficients Yx at x>6mm. The designed system performs algorithmic variable frequency protocols covering up 1,200 cm2. Duty factor control limits skin temperatures below 43°C irrespective pulse modulating frequency. mechanistic model PBM, phenomenologically consistent photon penetration studies, COVID trajectories, patient recovery profiles presented. Part II details various case studies positive outcomes thereof confirming efficacious modality COVID-19.

Language: Английский

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Levels of Angiotensin and Kinin Metabolite Peptides Related to COVID-19 Severity

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

In addition to crucial roles in normal human biology, peptide metabolites of the renin–angiotensin (RAS) and kallikrein–kinin systems (KKS) have been reported be altered COVID-19 patients. Here, we evaluate new data on RAS KKS peptides patient serum obtained from a recently developed, fully validated, optimized stable isotope labeling LC-MS assay. We found that angiotensin (ANG) 1, 2, 1–5, 1–7 were downregulated compared COVID-free surrogate controls, while Brad, Brad 1–8, upregulated. This paper focuses uncovering possible diagnostic value these using receiver operating characteristic (ROC) analyses data. ROC plots confirmed all analyte 80 samples patients significantly "normal" values control samples. The best sensitivities selectivities for COVID vs no (both 99% sensitivity, 100% selectivity). then analyzed levels grouped according preassigned World Health Organization (WHO) Severity Index. differentiated with high WHO severity index those low moderate success, BRAD (73% 79% selectivity) Ang (75% 65% giving performance. Results suggest as biomarkers help identify serious cases at relatively early stages.

Language: Английский

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