Anti-inflammatory drugs and the renin-angiotensin-aldosterone system: Current knowledge and potential effects on early SARS-CoV-2 infection

Cabbab, Iris Louise N.; Manalo, Rafael Vincent M.

doi:10.1016/j.virusres.2020.198190

Cited by 12 publications

(12 citation statements)

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“…In clinical studies of small cohorts of COVID-19 patients, treatment with NSAIDs was associated with either adverse clinical outcomes ( Jeong et al, 2020 ) or no effect on mortality rate ( Abu Esba et al, 2020 ; Chandan et al, 2020 ; Lund et al, 2020 ) or a modest beneficial effect on survival rates ( Bruce et al, 2020 ). The mechanisms of NSAID actions and their potential use in COVID-19 patients have recently been discussed ( Cabbab & Manalo, 2020 ; Micallef, Soeiro, & Jonville-Béra, 2020 ). The effects of steroids, NSAIDs, and pharmacologically related compounds on ACE2 activity and expression are summarized in Table 6 .…”

Section: Corticosteroids Non-steroid Anti-inflammatory Drugs and Acmentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

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The recent emergence of coronavirus disease-2019 (COVID-19) as a global pandemic has prompted scientists to address an urgent need for defining mechanisms of disease pathology and treatment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, employs angiotensin converting enzyme 2 (ACE2) as its primary target for cell surface attachment and likely entry into the host cell. Thus, understanding factors that may regulate the expression and function of ACE2 in the healthy and diseased body is critical for clinical intervention. Over 66% of all adults in the United States are currently using a prescription drug and while earlier findings have focused on possible upregulation of ACE2 expression through the use of renin angiotensin system (RAS) inhibitors, mounting evidence suggests that various other widely administered drugs used in the treatment of hypertension, heart failure, diabetes mellitus, hyperlipidemias, coagulation disorders, and pulmonary disease may also present a varied risk for COVID-19. Specifically, we summarize mechanisms on how heparin, statins, steroids and phytochemicals, besides their established therapeutic effects, may also interfere with SARS-CoV-2 viral entry into cells. We also describe evidence on the effect of several vitamins, phytochemicals, and naturally occurring compounds on ACE2 expression and activity in various tissues and disease models. This comprehensive review aims to provide a timely compendium on the potential impact of commonly prescribed drugs and pharmacologically active compounds on COVID-19 pathology and risk through regulation of ACE2 and RAS signaling.

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Section: Corticosteroids Non-steroid Anti-inflammatory Drugs and Acmentioning

confidence: 99%

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Öz

Lorke

Kabbani

2021

Pharmacology & Therapeutics

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“…SARS-CoV-2 enters respiratory epithelial cells via ACE2 interactions, causing receptor internalization and subsequent down-regulation (21). Reduced ACE2 levels, which have been shown to regulate RAS, could lead to RAS dysfunction, potentially enhancing inflammation and airway vascular permeability (22).…”

Section: Renin-angiotensin System (Ras) Dysfunctionmentioning

confidence: 99%

Tailoring glucocorticoids in patients with severe COVID-19: a narrative review

Luo¹,

Qian²,

Huang³

et al. 2021

Ann Transl Med

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To discuss the pathogenesis of severe coronavirus disease 2019 (COVID-19) infection and the pharmacological effects of glucocorticoids (GCs) toward this infection. To review randomized controlled trials (RCTs) using GCs to treat patients with severe COVID-19, and investigate whether GC timing, dosage, or duration affect clinical outcomes. Finally. to discuss the use of biological markers, respiratory parameters, and radiological evidence to select patients for improved GC therapeutic precision.Background: COVID-19 has become an unprecedented global challenge. As GCs have been used as key immunomodulators to treat inflammation-related diseases, they may play key roles in limiting disease progression by modulating immune responses, cytokine production, and endothelial function in patients with severe COVID-19, who often experience excessive cytokine production and endothelial and reninangiotensin system (RAS) dysfunction. Current clinical trials have partially proven this efficacy, but GC timing, dosage, and duration vary greatly, with no unifying consensus, thereby creating confusion.Methods: Publications through March 2021 were retrieved from the Web of Science and PubMed. Results from cited references in published articles were also included.Conclusions: GCs play key roles in treating severe COVID-19 infections. Pharmacologically, GCs could modulate immune cells, reduce cytokine and chemokine, and improve endothelial functions in patients with severe COVID-19. Benefits of GCs have been observed in multiple clinical trials, but the timing, dosage and duration vary across studies. Tapering as an option is not widely accepted. However, early initiation of treatment, a tailored dosage with appropriate tapering may be of particular importance, but evidence is inconclusive and more investigations are needed. Biological markers, respiratory parameters, and radiological evidence could also help select patients for specific tailored treatments.

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“…The World Health Organization (WHO) initially recommended that ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in the management of COVID-19 symptoms as there were anecdotal reports that NSAIDs such as ibuprofen could worsen effects of SARS-CoV-2 during the early phase of COVID-19[ 22 ]. WHO later withdrew their recommendation because of a lack of clinical evidence[ 22 ]. Indeed, Rinott and colleagues[ 23 ] reported that ibuprofen use was not associated with worse clinical outcomes when compared to paracetamol or no antipyretic use.…”

Section: Non-steroidal Anti-inflammatory Drugs and Paracetamolmentioning

confidence: 99%

“…22 WHO later withdrew their recommendation because of a lack of clinical evidence. 22 Indeed, Rinott and colleagues 23 reported that ibuprofen use was not associated with worse clinical outcomes when compared with paracetamol or no antipyretic use.…”

Section: Nsaids and Paracetamolmentioning

confidence: 99%

Anaesthesia-related drugs and SARS-CoV-2 infection

Hirota

Lambert

2021

British Journal of Anaesthesia

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EditordAlthough there is extensive discussion of COVID anaesthesia management and infection control in the operating theatre, there are few articles examining whether perioperative anaesthesia-related drugs could affect COVID-19. Here, we discuss this possibility.SARS-CoV-2 binding sites (Fig. 1) Angiotensin converting enzyme 2 Angiotensin converting enzyme 2 (ACE2) is the best-known target cell receptor for SARS-CoV-2 internalisation. It is widely distributed in human cells and tissues and highly expressed in the small intestine, testes, kidneys, heart, thyroid, lungs, salivary glands, and adipose tissues, but not in the vocal folds, epiglottis, and trachea. 1 Sigma-1 receptor SARS-CoV-2 interacts with sigma receptors via non-structural protein 6 and coronavirus open reading frame (Orf) 9c proteins to infect cells. 2 Knockout and knockdown of sigma-1 receptor (Sig-1R), but not of Sig-2R, decreased SARS-CoV-2 replication. Modulation of Sig-1R may thus affect the early steps of viral endocytosis to change SARS-CoV-2 infection for immunologic enhancement. 3

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Anti-inflammatory drugs and the renin-angiotensin-aldosterone system: Current knowledge and potential effects on early SARS-CoV-2 infection

Cited by 12 publications

References 100 publications

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

Tailoring glucocorticoids in patients with severe COVID-19: a narrative review

Anaesthesia-related drugs and SARS-CoV-2 infection

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