Thematic Article
Volume 9 Issue 4 - 2021
Renin-Angiotensin System, SARS-CoV-2 and Hypotheses about Adverse Effects Following Vaccination
Paolo Bellavite*
Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy
*Corresponding Author: Paolo Bellavite, Department of Medicine, Section of General Pathology, University of Verona, Verona, Italy.
Received: March 15, 2021; Published: March 30, 2021




Abstract

Coronavirus disease 2019 (COVID-19) affects the lungs but also the cardiovascular system, especially since the spike protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) uses the angiotensin-converting enzyme 2 (ACE2), existing on the membrane of many cell species, as a receptor. This connection has consequences on the renin-angiotensin system, arterial pressure and coagulation. An imbalance of blood pressure control, of coagulation and platelet functions, and of the kinin-kallikrein system may occur in natural disease but is also partly reflected in some possible negative consequences following vaccination. Knowledge of these mechanisms could help to identify the subjects most at risk of complications and to correctly carry out the causality assessment of adverse events.

Keywords: COVID-19; Renin-Angiotensin System; ACE2; Vaccination; Spike Protein; Arterial Pressure; Kinine System; Immunopharmacology; Thrombosis

References

  1. Alifano M., et al. “Renin-angiotensin system at the heart of COVID-19 pandemic”. Biochimie 174 (2020): 30-33.
  2. Verdecchia P., et al. “The pivotal link between ACE2 deficiency and SARS-CoV-2 infection”. European Journal of Internal Medicine 76 (2020): 14-20.
  3. Barrera FJ., et al. “Prevalence of Diabetes and Hypertension and Their Associated Risks for Poor Outcomes in Covid-19 Patients”. Journal of the Endocrine Society 9 (2020): bvaa102.
  4. Puliyel J and Naik P. “Revised World Health Organization (WHO)'s causality assessment of adverse events following immunization-a critique”. F1000 Research 7 (2018): 243.
  5. Bellavite P. “Causality assessment of adverse events following immunization: the problem of multifactorial pathology”. F1000 Research 9 (2020): 170.
  6. Bellavite P and Donzelli A. “Adverse events following measles-mumps-rubella-varicella vaccine: an independent perspective on Italian pharmacovigilance data”. F1000 Research 9 (2020): 1176.
  7. Du F., et al. “COVID-19: the role of excessive cytokine release and potential ACE2 down-regulation in promoting hypercoagulable state associated with severe illness”. The Journal of Thrombosis and Thrombolysis (2020): 1-17.
  8. Lu J and Sun PD. “High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity”. Journal of Biological Chemistry52 (2020): 18579-18588.
  9. Ramlall V., et al. “Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection”. Nature Medicine 10 (2020): 1609-1615.
  10. Liu PP., et al. “The Science Underlying COVID-19: Implications for the Cardiovascular System”. Circulation1 (2020): 68-78.
  11. Oz M and Lorke DE. “Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury”. Biomedicine and Pharmacotherapy 136 (2021): 111193.
  12. Davidson AM., et al. “Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor: Therapeutic Implications”. Hypertension5 (2020): 1339-1349.
  13. Pang J., et al. “Friend or Foe? ACE2 inhibitors and GLP-1R agonists in COVID-19 treatment”. Obesity Medicine (2021): 100312.
  14. Albashir AAD. “Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors and Coronavirus Disease 2019 (COVID-19)”. Southern Medical Journal 1 (2021): 51-56.
  15. Costa LB., et al. “Insights on SARS-CoV-2 Molecular Interactions With the Renin-Angiotensin System”. Frontiers in Cell and Developmental Biology 8 (2020): 559841.
  16. Rahman MM., et al. “Potential detrimental role of soluble ACE2 in severe COVID-19 comorbid patients”. Reviews in Medical Virology (2021).
  17. Rojas A., et al. “SARS-CoV-2-mediated inflammatory response in lungs: should we look at RAGE?” Inflammation Research 7 (2020): 641-643.
  18. Kaplan AP and Joseph K. “Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway”. Advances in Immunology 121 (2014): 41-89.
  19. McCarthy CG., et al. “A new storm on the horizon in COVID-19: Bradykinin-induced vascular complications”. Vascular Pharmacology (2020): 106826.
  20. Garvin MR., et al. “A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm”. Elife (2020): 9.
  21. Sidarta-Oliveira D., et al. “SARS-CoV-2 receptor is co-expressed with elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells”. Scientific Reports1 (2020): 19522.
  22. Lippi G., et al. “Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19)”. Annals of Clinical Biochemistry3 (2020): 262-265.
  23. Cervellin G., et al. “Serum potassium levels inversely correlate with D-dimer in patients with acute-onset atrial fibrillation”. Arquivos Brasileiros de Cardiologia 3 (2015): 181-184.
  24. Roche JA and Roche R. “A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications”. The FASEB Journal6 (2020): 7265-7269.
  25. Muslim S., et al. “Treatment Options Available for COVID-19 and an Analysis on Possible Role of Combination of rhACE2, Angiotensin (1-7) and Angiotensin (1-9) as Effective Therapeutic Measure”. SN Comprehensive Clinical Medicine 22 (2020): 1-6.
  26. Fratta Pasini AM., et al. “Potential Role of Antioxidant and Anti-Inflammatory Therapies to Prevent Severe SARS-Cov-2 Complications”. Antioxidants 2 (2021): 272.
  27. Bernard I., et al. “Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19”. Viruses1 (2020): 29.
  28. Pellegrini D., et al. “Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study”. Circulation10 (2021): 1031-1042.
  29. Zhang S., et al. “SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19”. Journal of Hematology and Oncology 1 (2020): 120.
  30. Nuovo GJ., et al. “Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein”. Annals of Diagnostic Pathology 51 (2021): 151682.
  31. Petrone L., et al. “A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients”. Clinical Microbiology and Infection (2020).
  32. Hester CG and Frank MM. “Complement activation by IgG containing immune complexes regulates the interaction of C1q with its ligands”. Molecular Immunology 116 (2019): 117-130.
  33. Wang K., et al. “Elevated Angiotensin 1-7/Angiotensin II Ratio Predicts Favorable Outcomes in Patients With Heart Failure”. Circulation: Heart Failure7 (2020): e006939.
  34. Bellavite P., et al. “A colorimetric method for the measurement of platelet adhesion in microtiter plates”. Analytical Biochemistry 2 (1994): 444-450.
  35. Suzuki YJ and Gychka SG. “SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Host Cells: Implications for Possible Consequences of COVID-19 Vaccines”. Vaccines1 (2021).
  36. Causality assessment of an adverse event following immunization (AEFI): user manual for the revised WHO classification (Second edition). 2nd Edition edn. Geneva: World Health Organization (2018).
Citation: Paolo Bellavite. “Renin-Angiotensin System, SARS-CoV-2 and Hypotheses about Adverse Effects Following Vaccination”. EC Pharmacology and Toxicology 9.4 (2021): 01-10.

PubMed Indexed Article


EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005


EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777


EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347


EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478


EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253


EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033


EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992


EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505


EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793


EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211


EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047


EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560


EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318


EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


News and Events


April Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the April issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before May 04, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to editor@ecronicon.uk