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COVID's Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19.

ABSTRACT: A modern iteration of Occam's Razor posits that "the simplest explanation is usually correct." Coronavirus Disease 2019 involves widespread organ damage and uneven mortality demographics, deemed unexpected from what was originally thought to be "a straightforward respiratory virus." The simplest explanation is that both the expected and unexpected aspects of COVID-19 share a common mechanism. Silent hypoxia, atypical acute respiratory distress syndrome (ARDS), stroke, olfactory loss, myocarditis, and increased mortality rates in the elderly, in men, in African-Americans, and in patients with obesity, diabetes, and cancer-all bear the fingerprints of the renin-angiotensin system (RAS) imbalance, suggesting that RAS is the common culprit. This article examines what RAS is and how it works, then from that baseline, the article presents the evidence suggesting RAS involvement in the disparate manifestations of COVID-19. Understanding the deeper workings of RAS helps one make sense of severe COVID-19. In addition, recognizing the role of RAS imbalance suggests potential routes to mitigate COVID-19 severity.

SUBMITTER: Czick M

PROVIDER: S-EPMC7495349 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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COVID's Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19.

Czick Maureen M Shapter Christine C Shapter Robert R

Diabetes, metabolic syndrome and obesity : targets and therapy 20200911

A modern iteration of Occam's Razor posits that "the simplest explanation is usually correct." Coronavirus Disease 2019 involves widespread organ damage and uneven mortality demographics, deemed unexpected from what was originally thought to be "a straightforward respiratory virus." The simplest explanation is that both the expected and unexpected aspects of COVID-19 share a common mechanism. Silent hypoxia, atypical acute respiratory distress syndrome (ARDS), stroke, olfactory loss, myocarditis ...[more]

PMID: 32982349

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Project description:Vaccine hesitancy and refusal to be vaccinated are major reasons why mass vaccination strategies do not reach the intended coverage, even if adequate vaccine supply has been achieved. The main objective of this study is to explore the role and contribution of trust in public willingness to accept COVID-19 vaccinations. The study utilised a qualitative synthesis of literature around hesitancy, willingness to accept vaccination, and the role of trust. Data were extracted from the literature and first categorised using a deductive approach, and later analysed in QSR NVivo using a mix of deductive and inductive approaches. The impact of trust was mostly borne out in the willingness to accept a vaccine, but details on what trust is, how and why it affects willingness or lack of it, was not frequently reported. Three types of trust were identified: 1) Trust in the quality and safety of vaccines; 2) Institutional trust; and 3) Interpersonal trust in the professionals who communicate about and administer the vaccine. Trust in the vaccines' quality and safety, and institutional affiliation significantly contributed towards willingness to be vaccinated. The bulk of the literature focused on how interpersonal trust and personal attributes of potential vaccinees affected the willingness to accept the vaccine. This complex relationship included a fragility of beliefs and perceptions at an individual level, with a bidirectional relationship to societal perceptions. Perceptions of vaccines had a predominant role in decision-making, in contrast to more science-based decision-making. Although globally, the perceptions and beliefs contributing to trust had commonalities and relevance, trust was often found to be dependent on factors embedded in local social, cultural, institutional, and individual attributes and experiences. Understanding different types of trust offers potential approaches to motivate undecided people to receive vaccine; and vaccine refusers to revisit their decisions.

Project description:BackgroundThe pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required.MethodsCOVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome.ResultsSignificantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects.ConclusionHerein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.

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COVID's Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19.

Publications

COVID's Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19.

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