Renin-Angiotensin-Aldosterone Inhibitors and Susceptibility to and Severity of COVID-19

Curfman, Gregory D.

doi:10.1001/jama.2020.11401

Cited by 15 publications

(14 citation statements)

References 7 publications

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“…29 Even if ACEi/ARB do upregulate ACE2 receptors, which they may 30 or may not, 31 the absence of upregulation of TMPRSS2 may inhibit enhanced viral entry into cells. 28 Our study is limited by the fact that it was observational and thus may have been subject to bias and confounding. We conducted a propensity score-matched analysis to reduce as far as possible biases when estimating treatment effects.…”

Section: Discussionmentioning

confidence: 98%

Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

Bauer

Gore

Sama

et al. 2020

J of Clinical Hypertension

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It remains uncertain whether the hypertension (HT) medications angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS‐CoV‐2 infection. We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID‐19) as defined by hospitalization or mortality among individuals diagnosed with COVID‐19. We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use. In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID‐19 diagnosis. In our study, pre‐infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID‐19. Risk was further elevated in patients under age 65 with these comorbidities or cancer. Twenty percent of those with severe COVID‐19 compared to 9% with less severe COVID‐19 used ACEi, 8% and 4%, respectively, used ARB. In propensity score‐matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID‐19. Thiazide use did not modify this relationship. Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID‐19 severity. In conclusion, cardiovascular‐related comorbidities were associated with severe COVID‐19 outcomes, especially among patients under age 65. We found no substantial increased risk of severe COVID‐19 among patients taking antihypertensive medications. Our findings support recommendations against discontinuing use of renin–angiotensin system (RAS) inhibitors to prevent severe COVID‐19.

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Section: Discussionmentioning

confidence: 98%

Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

Bauer

Gore

Sama

et al. 2020

J of Clinical Hypertension

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“…Both of these large studies demonstrated that the use of an ACEi and ARB is not associated with an increased risk of infection with SARS-CoV-2. Thus, these agents should not be discontinued, unless the drugs cannot be tolerated due to hemodynamic instability [126]. If a COVID-19 patient has an indication for these agents, therapy should be started or continued.…”

Section: Renin-angiotensin-aldosterone System Inhibitorsmentioning

confidence: 99%

Pharmaco-Immunomodulatory Therapy in COVID-19

Rizk

Kalantar-Zadeh

Mehra

et al. 2020

Drugs

255

244

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The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colonystimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms. Key Points COVID-19 is a syndrome of viral replication and a host inflammatory response. Tackling the immune response may be as important as addressing viral replication. Specific and non-specific immune modulators have the potential to inhibit cytokines and quell the cytokine storm.

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“…Ethnicity may also be important, with patients in the United Kingdom of Bangladesh origin having appreciably increased mortality from COVID-19 [66][67][68][69] . There were concerns initially that renin-angiotensin inhibitors would enhance susceptibility to COVID-19, as well as increase its severity, leading to recommendations to stop these treatments, which is a concern in Bangladesh given current high prevalence rates of CVD, diabetes, and hypertension 17,19,20,70 . However encouragingly, recent studies have shown no such association 71,72 .…”

Section: Risk Factors and Approaches To Prevent And Treat Covid-19 -Gmentioning

confidence: 99%

Availability and price changes of potential medicines and equipment for the prevention and treatment of COVID-19 among pharmacy and drug stores in Bangladesh; findings and implications

Haque

Islam

Iqbal

et al. 2020

Bangladesh J Med Sci

107

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Objective: There are concerns with increased prices and drug shortages for pertinent medicines and personal protective equipment (PPE) to prevent and treat COVID-19 enhanced by misinformation. Community pharmacists and drug stores play a significant role in disease management in Bangladesh due to high co-payments. Consequently, a need to review prices and availability in the pandemic. Materials and Methods: Multiple approach involving a review and questionnaire among pharmacies and stores early March to end May 2020. Results and Discussion: 170 pharmacies and drug stores took part, giving a response rate of 63.9%. Encouragingly, no change in utilization of antimalarial medicines in 51.2% of stores despite global endorsements. However, increased utilisation of antibiotics (70.6%), analgesics (97.6%), vitamins (90.6%) and PPE (over 95%). Encouragingly, increases in purchasing of PPE. No increase in prices among 50% of the stores for antimalarials, with a similar situation for antibiotics (65.3%), analgesics (54.7%), and vitamins (51.8%). However, price increases typically for PPE (over 90% of stores). Shortages also seen for medicines and PPE, again greater for PPE. Conclusions: The pandemic has impacted on the supply and prices of medicines and PPE in Bangladesh. Key stakeholder groups can play a role addressing misinformation, with enhanced local production helping address future shortages and prices. Bangladesh Journal of Medical Science Vol.19(0) 2020 p. S 36-S 50

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Renin-Angiotensin-Aldosterone Inhibitors and Susceptibility to and Severity of COVID-19

Cited by 15 publications

References 7 publications

Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study

Pharmaco-Immunomodulatory Therapy in COVID-19

Availability and price changes of potential medicines and equipment for the prevention and treatment of COVID-19 among pharmacy and drug stores in Bangladesh; findings and implications

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