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Archive for the ‘SARS-COV2 Hijacking the Complement and Coagulation Systems’ Category


Bradykinin Hypothesis: Potential Explanation for COVID-19

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED on 9/14/2020

First Randomized Trial Backs Safety of ACE and ARB Heart Drugs in COVID-19 Patients

BRACE CORONA trial presented in a Hot Line Session at ESC Congress 2020

September 8, 2020 – Heart patients hospitalized with COVID-19 (SARS-CoV-2) can safely continue taking angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), according to the BRACE CORONA trial presented in a Hot Line session at the virtual European Society of Cardiology (ESC) Congress 2020.[1]

ACE inhibitors and ARBs are commonly taken by heart patients to reduce blood pressure and to treat heart failure. There is conflicting observational evidence about the potential clinical impact of ACE inhibitors and ARBs on patients with COVID-19.[2] Select preclinical investigations have raised concerns about their safety in patients with COVID-19. Preliminary data hypothesize that renin-angiotensin-aldosterone system (RAAS) inhibitors could benefit patients with COVID-19 by decreasing acute lung damage and preventing angiotensin-II-mediated pulmonary inflammation.

Given the frequent use of these agents worldwide, randomized clinical trial evidence is urgently needed to guide the management of patients with COVID-19.

SOURCE

https://www.dicardiology.com/content/first-randomized-trial-backs-safety-ace-and-arb-heart-drugs-covid-19-patients

Related ACE and ARB Content Related to COVID-19:

ESC Council on Hypertension Says ACE-I and ARBs Do Not Increase COVID-19 Mortality

AHA Explains Severe COVID-19 is Closely Associated With Heart Issues

 

The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

Justin D. Pearlman, MD, PhD, FACC – Scientific Expert & Key Opinion Leader on Cardiovascular Diseases, Cardiac Imaging & Complex Diagnosis in Cardiology: Senior Editor & Author

The BRACE CORONA TRIAL compared outcomes for COVID19 patients previously on ACE inhibitor or ARB of holding the medication for a month, or not, and saw no significant benefit from withholding either class of medication. The basis for specific concern is the fact that the COVID19 virus utilizes ACE2 receptors for its invasion, and that disturbances in the renin-angiotensin and bradykinin levels and capillary leak have been observed with COVID19 infections. ACEI and ARB medications both modulate the renin angiotensin system, but with different impact on bradykinin levels. Changes in bradykinin levels cause for dry cough seen with ACE inhibitors like lisinopril that are not seen with angiotensin receptor blockers (ARB) such as Losartan. The absence of significant differences in outcome measures by holding either drug weakens the Jacobson’s bradykinin hypothesis based on a cascade of observations related to the ACE2 receptor and downstream effects. The new observations on safety of both ACEI and ARB weaken Jacobson’s hypothesis of a primary importance of renin angiotensin and bradykinin changes in the course and complications of COVID19 infection.

The ACE gene product degrades bradykinin. Jacobson’s bradykinin hypothesis suggested that the observations of capillary leak and disturbances in the renal angiotensin system may be prime factors rather than bystanders. Jacobson made strong statements from associations, but the lack of impact of stoppage of either ACE inhibitors or Angiotensin Receptor Blockers (ARB) argues that his observations are not major in determination of outcomes.

Bradykinin Hypothesis: Potential Explanation for COVID-19

The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS. Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2.

critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. These bradykinin-driven outcomesexplain many of the symptoms being observed in COVID-19.

Jacobson says, “What we’ve found is that the imbalance in the renin-angiotensin system (RAS) pathway that appeared to be present in Covid-19 patients could be responsible for constantly resensitizing bradykinin receptors. So, this imbalance in the RAS pathways will take the brakes off the bottom of the bradykinin pathway at the receptor level. In addition, the downregulation of the ACE gene in Covid-19 patients, which usually degrades bradykinin, is another key imbalance in the regulation of bradykinin levels. We have also observed that the key negative regulator at the top of the bradykinin pathway is dramatically down-regulated. Thus, you likely have an increase in bradykin production as well, stopping many of the braking mechanisms usually in place, so the bradykinin signal spirals out of control.”

The bradykinin hypothesis also extends to many of Covid-19’s effects on the heart. About one in five hospitalized Covid-19 patients have damage to their hearts, even if they never had cardiac issues before. Some of this is likely due to the virus infecting the heart directly through its ACE2 receptors. But the RAS also controls aspects of cardiac contractions and blood pressure. According to the researchers, bradykinin storms could create arrhythmias and low blood pressure, which are often seen in Covid-19 patients.

“the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,” which had been previously identified in Covid-19 patients, but that “the two may be intricately linked.”

According to Jacobson and his team, MRI studies in France revealed that many Covid-19 patients have evidence of leaky blood vessels in their brains.

bradykinin would indeed be likely to increase the permeability of the blood-brain barrier. In addition, similar neurological symptoms have been observed in other diseases that result from an excess of bradykinin.”

Increased bradykinin levels could also account for other common Covid-19 symptoms. ACE inhibitors — a class of drugs used to treat high blood pressure — have a similar effect on the RAS system as Covid-19, increasing bradykinin levels. In fact, Jacobson and his team note in their paper that “the virus… acts pharmacologically as an ACE inhibitor” — almost directly mirroring the actions of these drugs.

SOURCE

https://elifesciences.org/articles/59177?utm_source=Unknown+List&utm_campaign=7a5785d58d-EMAIL_CAMPAIGN_2020_07_27_02_37&utm_medium=email&utm_term=0_-7a5785d58d-

Potential therapeutic development path is to

  • repurpose existing FDA approved drugs such as Danazol, Stanasolol, Icatibant, Ecallantide, Berinert, Cynryze, Haegarda, etc.. to reduce the amount of bradykinin signaling to prevent the escalation of the bradykinin storm.
  • Partnerships with pharmaceutical companies and clinical research are needed to design and implement the right clinical trials to see how these types of treatments can be applied.
  • Systems biology perspective and think that attempts to inhibit the virus itself will also probably require a combinatorial strategy it’s possible that we will need a combinatorial approach to therapies both on the human side and on the viral side
  • Other compounds could treat symptoms associated with bradykinin storms. Hymecromone, for example, could reduce hyaluronic acid levels, potentially stopping deadly hydrogels from forming in the lungs. And timbetasin could mimic the mechanism that the researchers believe protects women from more severe Covid-19 infections

https://www.forbes.com/sites/cognitiveworld/2020/08/05/your-lungs-can-fill-up-with-jell-o-scientists-discover-a-new-pathway-for-covid-19-inflammatory-response/#7a80ff4c24be

 

A Supercomputer Analyzed Covid-19 — and an Interesting New Theory Has Emerged

A closer look at the Bradykinin hypothesis

Thomas Smith Sep 1, 2020

Earlier this summer, the Summit supercomputer at Oak Ridge National Lab in Tennessee set about crunching data on more than 40,000 genes from 17,000 genetic samples in an effort to better understand Covid-19. Summit is the second-fastest computer in the world, but the process — which involved analyzing 2.5 billion genetic combinations — still took more than a week.

When Summit was done, researchers analyzed the results. It was, in the words of Dr. Daniel Jacobson, lead researcher and chief scientist for computational systems biology at Oak Ridge, a “eureka moment.” The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis. The hypothesis provides a model that explains many aspects of Covid-19, including some of its most bizarre symptoms. It also suggests 10-plus potential treatments, many of which are already FDA approved. Jacobson’s group published their results in a paper in the journal eLife in early July.

According to the team’s findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease’s cardiac and GI symptoms.

https://elemental.medium.com/a-supercomputer-analyzed-covid-19-and-an-interesting-new-theory-has-emerged-31cb8eba9d63

Researchers Use Supercomputers To Discover New Pathway For Covid-19 Inflammation

COGNITIVE WORLD

A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm

  1. Michael R Garvin
  2. Christiane Alvarez
  3. J Izaak Miller
  4. Erica T Prates
  5. Angelica M Walker
  6. B Kirtley Amos
  7. Alan E Mast
  8. Amy Justice
  9. Bruce Aronow
  10. Daniel JacobsonIs a corresponding author
  1. Oak Ridge National Laboratory, Biosciences Division, United States
  2. University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, United States
  3. University of Kentucky, Department of Horticulture, United States
  4. Versiti Blood Research Institute, Medical College of Wisconsin, United States
  5. VA Connecticut Healthcare/General Internal Medicine, Yale University School of Medicine, United States
  6. University of Cincinnati, United States
  7. Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, United States
  8. University of Tennessee Knoxville, Department of Psychology, Austin Peay Building, United States

Abstract

Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS. Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2.Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. These bradykinin-driven outcomes explain many of the symptoms being observed in COVID-19.

https://elifesciences.org/articles/59177?utm_source=Unknown+List&utm_campaign=7a5785d58d-EMAIL_CAMPAIGN_2020_07_27_02_37&utm_medium=email&utm_term=0_-7a5785d58d-

Short Report 

https://www.forbes.com/sites/cognitiveworld/2020/08/05/your-lungs-can-fill-up-with-jell-o-scientists-discover-a-new-pathway-for-covid-19-inflammatory-response/#7a80ff4c24be

A hypothesized role for dysregulated bradykinin signaling in COVID‐19 respiratory complications

1 Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit MI, USA,
2 College of Health and Human Services, Eastern Michigan University, Ypsilanti MI, USA,
Joseph A. Roche, ude.enyaw@ehcor.hpesoj.
corresponding authorCorresponding author.
*Correspondence
Joseph A. Roche, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, USA.
Email: ude.enyaw@ehcor.hpesoj,

Abstract

As of April 20, 2020, over time, the COVID‐19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des‐Arg(9)‐bradykinin‐ and bradykinin‐mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID‐19. Through our hypothesis, we make the prediction that the FDA‐approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID‐19 morbidity and mortality.

Keywords: bradykinin, bradykinin receptor, coronavirus, icatibant, inflammation, injury

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267506/

 

 

Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome

Frank L van de Veerdonk1*, Mihai G Netea1,2, Marcel van Deuren1,

Jos WM van der Meer1, Quirijn de Mast1, Roger J Bru¨ggemann3,

Hans van der Hoeven4

van de Veerdonk et al. eLife 2020;9:e57555. DOI: https://doi.org/10.7554/eLife.57555 1 of 9

Abstract

COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. Here, we hypothesize that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19. We propose that blocking the B2R and inhibiting plasma kallikrein activity might have an ameliorating effect on early disease caused by COVID-19 and might prevent acute respiratory distress syndrome (ARDS). In addition, this pathway might indirectly be responsive to anti-inflammatory agents.

 

Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach

Frank L. van de Veerdonk1*, Mihai G. Netea1,2, Marcel van Deuren1, Jos W.M. van der Meer1, Quirijn de Mast1, Roger J. Brüggemann3, Hans van der Hoeven4

doi:10.20944/preprints202004.0023.v1

Abstract

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that antiinflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

 

Emerging Pandemic Diseases: How We Got to COVID-19

David M. Morens1,* and Anthony S. Fauci1

1Office of the Director, National Institute of Allergy & Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

*Correspondence: dm270q@nih.gov

https://doi.org/10.1016/j.cell.2020.08.021

SUMMARY

Infectious diseases prevalent in humans and animals are caused by pathogens that once emerged from other animal hosts. In addition to these established infections, new infectious diseases periodically emerge. In extreme cases they may cause pandemics such as COVID-19; in other cases, dead-end infections or smaller epidemics result. Established diseases may also re-emerge, for example by extending geographically or by becoming more transmissible or more pathogenic. Disease emergence reflects dynamic balances and imbalances, within complex globally distributed ecosystems comprising humans, animals, pathogens, and the environment. Understanding these variables is a necessary step in controlling future devastating disease emergences.

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Why Blood Clots Are a Major Problem in Severe COVID-19

Reporter: Aviva Lev-Ari, PhD, RN

 

  • Clotting in uninjured blood vessels is a common occurrence in hospital patients, especially those in the intensive care unit.

  • In a July report in the journal Blood, Al-Samkari and colleagues found that nearly 10 percent of 400 people hospitalized for Covid-19 developed clots. In a February report by researchers in China, about 70 percent of people who died of Covid-19 had widespread clotting, while few survivors did.
  • people who died of Covid-19 were nine times as likely to be speckled with tiny clots as those of people who died of influenza
  • SARS-CoV-2 infects and damages the cells lining blood vessels, it could expose the tissue underneath
  • clotting results from inflammation. And here, many experts are eyeing a set of proteins called the complement system
  • These proteins, known collectively as complement, attack invaders and call in other parts of the immune system to assist. They also can activate platelets and promote clotting.
  • Claudia Kemper1,2,3 said “complementologists think that this is a massive part of the disease”  signs of complement activity in the lungs and livers of people who died from Covid-19
  • Laurence found several active complement proteins in the skin and blood vessels of his early Covid-19 clotting cases
  • a New York team found that patients were more likely to become very ill and die if they had a history of clotting or bleeding, or if they had macular degeneration, which can indicate complement problems.
  • Genes involved in complement and clotting responses were more active when the virus was present in patients’ nasal swabs.
  • immune element may promote clotting in severe Covid-19 cases: an overreaction called a cytokine storm, in which the body releases an excess of inflammation-promoting cytokine molecules.
  • Body’s response in need of control: (1) control the clotting, (2) control the inflammation, (2) control the complement pathway in tandem with antiviral Remdesivir that controls the viral replication thus the viral load.
  • Balance the risk of clotting with the danger of bleeding (bleeds into the digestive system for these patients, but they may also hemorrhage in the lungs, brain or spots where medical devices pierce the skin)
  • Dosage of blood thinners is debated – 40 Studies found for: anticoagulation | Covid19
    Also searched for COVID and SARS-CoV-2See Search Details
  • there is no evidence that people with less severe Covid-19, who do not require hospitalization, should take blood thinners or aspirin to ward off clots.
  • Management of Clotting: Argatroban, for example, is a Food and Drug Administration-approved anticoagulant that interferes with thrombin, an element of the clotting cascade. Eculizumab, which blocks one of the complement proteins, is approved for certain inflammatory conditions.
  • Clinical judgement is used in light of lack of evidence

 

SOURCES

Why Blood Clots Are a Major Problem in Severe Covid-19

SMITHSONIANMAG.COM

https://www.smithsonianmag.com/science-nature/why-blood-clots-are-major-problem-severe-covid-19-180975678/

Complement and the Regulation of T Cell Responses

Annual Review of Immunology

Vol. 36:309-338 (Volume publication date April 2018)
https://doi.org/10.1146/annurev-immunol-042617-053245

Complement Dysregulation and Disease: Insights from Contemporary Genetics

M. Kathryn Liszewski,1 Anuja Java,2

Elizabeth C. Schramm,3 and John P. Atkinson1

1Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; email: j.p.atkinson@wustl.edu

2Division of Nephrology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110

3Serion Inc., St. Louis, Missouri 63108

 

Keywords

atypical hemolytic uremic syndrome, age-related macular degeneration,

alternative complement pathway, C3 glomerulopathies, factor H, CD46,

factor I, C3, factor B

Abstract

The vertebrate complement system consists of sequentially interacting proteins that provide for a rapid and powerful host defense. Nearly 60 proteins comprise three activation pathways (classical, alternative, and lectin) and a terminal cytolytic pathway common to all. Attesting to its potency, nearly half of the system’s components are engaged in its regulation. An emerging theme over the past decade is that variations in these inhibitors predispose to two scourges of modern humans. One, occurring most often in childhood, is a rare but deadly thrombomicroangiopathy called atypical hemolytic uremic syndrome. The other, age-related macular degeneration, is the most common form of blindness in the elderly. Their seemingly unrelated clinical presentations and pathologies share the common theme of overactivity of the complement system’s alternative pathway. This review summarizes insights gained from contemporary genetics for understanding how dysregulation of this powerful innate immune system leads to these human diseases.

CONCLUSIONS AND PERSPECTIVES

Over the last decade, a remarkable advance has been the elucidation of the role of mutations in complement regulators and components in aHUS, AMD, and C3G. Next-generation sequencing has led theway to these discoveries, but functional assessments are the critical factors in definitively associating pathogenesis with genetic variants.

Most exciting has been the development and approval by the FDA of the monoclonal antibody, eculizumab, as the new standard of care for treatment of aHUS. Challenges remain, however because eculizumab is costly and the duration of treatment remains uncertain and warrants further prospective studies. The use of eculizumab in C3G should also be prospectively addressed.

Furthermore, given the increasing number of mutations in the complement regulatory proteins identified in aHUS and C3G and the heterogeneity in the mechanisms leading to dysregulation of the AP, there is a need for further assessment of the genetic variants of unknown significance. As yet, no complement inhibitor has been approved to treat AMD.

These analyses coupled with the anticipated new developments of complement therapeutics will help establish patient-tailored therapies based on each patient’s specific alteration. The future holds much promise for the further delineation of complement-disease associations and for novel complement-targeted therapeutic agents.

SOURCE

Annu. Rev. Pathol. Mech. Dis. 2017. 12:25–52

https://www.annualreviews.org/doi/10.1146/annurev-pathol-012615-044145

 

 

Other related articles published in this Open Access Online Scientific Journal include the following: 

 

Is SARS-COV2 Hijacking the Complement and Coagulation Systems?

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/08/04/is-sars-cov2-hijacking-the-complement-and-coagulation-systems/

 

New Etiology for COVID-19: Death results from Immune-Mediation (virus-independent immunopathology: lung and reticuloendothelial system) vs Pathogen-Mediation causing Organ Dysfunction & Hyper-Inflammation – Immunomodulatory Therapeutic Approaches (dexamethasone)

Curators: Stephen J. Williams and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/07/12/new-etiology-for-covid-19-death-results-from-immune-mediation-virus-independent-immunopathology-lung-and-reticuloendothelial-system-vs-pathogen-mediation-causing-organ-dysfunction-hyper-infl/

Corticosteroid, Dexamethasone Improves Survival in COVID-19: Deaths reduction by 1/3 in ventilated patients and by 1/5 in other patients receiving oxygen only

Reporter: Aviva Lev-Ari, PhD, RN – bold face and color fonts added

https://pharmaceuticalintelligence.com/2020/06/27/corticosteroid-dexamethasone-improves-survival-in-covid-19-deaths-reduction-by-1-3-in-ventilated-patients-and-by-1-5-in-other-patients-receiving-oxygen-only/

SAR-Cov-2 is probably a vasculotropic RNA virus affecting the blood vessels: Endothelial cell infection and endotheliitis in COVID-19

Reporter: Aviva Lev-Ari, PhD, RN – Bold face and colors are my addition

https://pharmaceuticalintelligence.com/2020/06/01/sar-cov-2-is-probably-a-vasculotropic-rna-virus-affecting-the-blood-vessels-endothelial-cell-infection-and-endotheliitis-in-covid-19/

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