&lt;p&gt;COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19&lt;/p&gt;

Czick, Maureen E.; Shapter, Christine; Shapter, Robert

doi:10.2147/dmso.s265518

Cited by 9 publications

(7 citation statements)

References 225 publications

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“…(Wiese et al, 2020) hypothesise that pathology in COVID-19 arises from an upregulation of the classical arm of the RAS pathway and a downregulation of the ‘protective arm’ of the RAS pathway. (Czick et al, 2020) suggest a role for RAS imbalance in multiple aspects of COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Marley

2020

Preprint

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BackgroundThe COVID-19 pandemic has claimed over 1 million lives globally and results from the SARS-COV2 virus. COVID-19 is associated with a coagulopathy. In this mixed-methods PRISMA-compliant scoping review, we set out to determine if ARDS, sepsis and DIC could account for the coagulopathy and if there were any other features of the coagulopathy we could determine so as to inform future research. Methods: We used a search strategy to identify papers with clinically relevant thromboembolic events in COVID-19. We then developed a technique referred to as an Abridged Thematic Analysis (ATA) to quickly identify themes in the papers so as to increase the yield of clinically relevant information. We further developed Validated Abridged Thematic Analysis (VATA) to validate the resulting taxonomy of themes. Finally we developed a number of methods that can be used by other researchers to take forwards this work. Results: We identified 56 studies with 10,523 patients, 456 patients with COVID-19 and thromboembolic events (TBE’s) and 586 thrombembolic events. There were an average of 1.3 TBE’s per patient. There were five main arterial territories with corresponding clinical sequelae: Acute limb ischaemia, myocardial infarcts, strokes, mesenteric ischaemia and pulmonary embolism. We also identified DVT’s. There were two further groups: medical-device-related coagulopathy and dermal lesions. In a subgroup of 119 patients we found mortality ranged from 26% in DVT to 79% in acute limb ischaemia although there was evidence of selection bias in the latter group. All patients were hospitalised and the average age of survivors was 63 versus 73 for those who died. 91/150 patients with TE’s had fever. From the ATA, we identified 16 characteristics of the clotting pathology in COVID-19. From the VATA, we identified 34 mechanisms leading to coagulopathy and grouped them according to Virchow’s triad of vascular damage, stasis and hypercoagulability. Coagulopathy occurred with and without each of ARDS, Sepsis and DIC. We conclude that COVID-19 leads to the syndrome of a viral clotting fever in a subgroup of patients and that the presentation of coagulopathy and fever should raise the possibility of COVID-19 as a differential. We make recommendations for future research studies.

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Section: Resultsmentioning

confidence: 99%

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Marley

2020

Preprint

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“…Large comprehensive studies that are consistent with this approach continue to appear in the literature 62 . An additional plausible element, increased generation and activity of bradykinin, has recently appeared within the cytokine storm aspect of this disease 63,64 . While each of these publications discusses potential specific therapy, it warrants noting that this bradykinin pathway is on record as being inhibited by the anti‐TNF therapy discussed here 65,66 …”

Section: Minimising the Harm Of A Cytokine Storm By Inhibiting Inflammatory Cytokinesmentioning

confidence: 89%

Background to new treatments for COVID‐19, including its chronicity, through altering elements of the cytokine storm

Clark

2020

Reviews in Medical Virology

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Summary Anti‐tumour necrosis factor (TNF) biologicals, Dexamethasone and rIL‐7 are of considerable interest in treating COVID‐19 patients who are in danger of, or have become, seriously ill. Yet reducing sepsis mortality by lowering circulating levels of TNF lost favour when positive endpoints in earlier simplistic models could not be reproduced in well‐conducted human trials. Newer information with anti‐TNF biologicals has encouraged reintroducing this concept for treating COVID‐19. Viral models have had encouraging outcomes, as have the effects of anti‐TNF biologicals on community‐acquired COVID‐19 during their long‐term use to treat chronic inflammatory states. The positive outcome of a large scale trial of dexamethasone, and its higher potency late in the disease, harmonises well with its capacity to enhance levels of IL‐7Rα, the receptor for IL‐7, a cytokine that enhances lymphocyte development and is increased during the cytokine storm. Lymphoid germinal centres required for antibody‐based immunity can be harmed by TNF, and restored by reducing TNF. Thus the IL‐7‐ enhancing activity of dexamethasone may explain its higher potency when lymphocytes are depleted later in the infection, while employing anti‐TNF, for several reasons, is much more logical earlier in the infection. This implies dexamethasone could prove to be synergistic with rIL‐7, currently being trialed as a COVID‐19 therapeutic. The principles behind these COVID‐19 therapies are consistent with the observed chronic hypoxia through reduced mitochondrial function, and also the increased severity of this disease in ApoE4‐positive individuals. Many of the debilitating persistent aspects of this disease are predictably susceptible to treatment with perispinal etanercept, since they have cerebral origins.

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“…A common mechanism is shared between both the anticipated and unexpected aspects of COVID-19: silent hypoxia, atypical acute respiratory distress syndrome (ARDS), stroke, loss of smell, myocarditis, and elevated mortality in the elderly, in men, in African Americans, and in obesity, diabetes, and cancer patients. All bear the fingerprints of the imbalance of the renin-angiotensin system (RAS), indicating that the common culprit is RAS [ 2 ]. We also add our daily and continuous observation and explanation as regards the role of anti-hepatitis C medications to protect hepatic patients to this theory.…”

Section: Evidence Synthesis For the Hypothesismentioning

confidence: 99%

Does mass management of chronic hepatitis C protect the Egyptian population against fulminant coronavirus disease-2019? “Postulating a hypothesis”

Negm

2022

Egypt J Bronchol

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Coronavirus disease (COVID-19) is caused by the pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Egypt has launched a national treatment program to provide a cure for Egyptian patients infected with hepatitis C virus (HCV). A common mechanism is shared between both the anticipated and unexpected aspects of COVID-19. The activity of the renin-angiotensin system (RAS) is intrinsically high in the lungs, which is a major source of ACE and hence a significant site of systemic synthesis of Ang II. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2, the etiological agent of the COVID-19 disease. ACE-2 and its angiotensin 1–7 (Ang 1–7) product, which acts on the Mas oncogene receptor, have been shown to play a protective role in fibrogenesis and inflammation of many organs, including the liver and lung. Antiviral treatment with interferon (IFN) in conjunction with ribavirin in patients with chronic hepatitis C reduces serum ACE activity and indirectly affects liver parenchyma fibrogenesis. The antifibrotic activity of sofosbuvir plus daclatasvir (SOF/DAC) is independent of its antiviral action. Elimination of HCV infection by DAA therapy in patients with chronic hepatitis C could improve natural killer (NK) activity by increasing the frequency of CD 16+ CD 56+ NK cells. COVID-19 individuals exhibit enhanced platelet activation and aggregation, as well as platelet-monocyte aggregation, which is linked to coagulative disorders. Lower systemic inflammation and enhanced hepatic synthesis of both pro- and anti-coagulant factors were noticed soon after antiviral therapy. In order to protect against the severity of COVID-19, treatment of chronic hepatitis C has been observed as a possible key as a prophylaxis beside the vaccine and should be tested for evidence or rejection of observation.

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<p>COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19</p>

Cited by 9 publications

References 225 publications

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Background to new treatments for COVID‐19, including its chronicity, through altering elements of the cytokine storm

Does mass management of chronic hepatitis C protect the Egyptian population against fulminant coronavirus disease-2019? “Postulating a hypothesis”

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