Adverse Outcomes and Mortality in Users of Non-Steroidal Anti-Inflammatory Drugs tested positive for SARS-CoV-2: A Danish Nationwide Cohort Study

Lund, Lars Christian; Kristensen, Kasper Bruun; Reilev, Mette; Christensen, Steffen; Thomsen, Reimar W.; Christiansen, Christian Fynbo; Støvring, Henrik; Johansen, Nanna Borup; Brun, Nikolai C.; Hallas, Jesper; Pottegaard, Anton

doi:10.1101/2020.06.08.20115683

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…However, our findings do not support this conjecture. Indeed, there are parallels between our results and those from previous studies investigating the impact of ibuprofen on the severity of COVID-19 in South Korea (16) and Denmark (17). In those studies, NSAIDs conferred no additional risk of morbidity or mortality.…”

Section: Discussionsupporting

confidence: 87%

“…Interestingly, Lund et al also attempted to examine the impact of age and sex on COVID‐19 severity in patients taking NSAIDs compared to their matched controls. They identified no clear differences in outcomes across age or sex, although the study may not have been sufficiently powered to identify these as potential effect modifiers (17).…”

Section: Discussionmentioning

confidence: 99%

“…In both reviews it was concluded that there was no clear association between NSAIDs and these outcomes but they noted that the evidence was scarce. Several studies examined the impact of NSAIDs on the disease course in patients with COVID-19 (16,17), including those with acute respiratory distress syndrome (18). However, smaller-scale clinical studies to date have been unable to adequately investigate whether use of NSAIDs could confer susceptibility to infection due to SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

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Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID‐19

Chandan

Zemedikun

Thayakaran

et al. 2021

Arthritis & Rheumatology

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Objective. To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.Methods. We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.Results. During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex. Conclusion.No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID‐19

Chandan

Zemedikun

Thayakaran

et al. 2021

Arthritis & Rheumatology

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Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment

et al. 2022

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A massive worldwide vaccination campaign constitutes the main tool against the COVID-19 pandemic. However, drug treatments are also necessary. Antivirals are the most frequently considered treatments. However, strategies targeting mechanisms involved in disease aggravation may also be effective. A major role of the tissue renin-angiotensin system (RAS) in the pathophysiology and severity of COVID-19 has been suggested. The main link between RAS and COVID-19 is angiotensin-converting enzyme 2 (ACE2), a central RAS component and the primary binding site for SARS-CoV-2 that facilitates the virus entry into host cells. An initial suggestion that the susceptibility to infection and disease severity may be enhanced by angiotensin type-1 receptor blockers (ARBs) and ACE inhibitors (ACEIs) because they increase ACE2 levels, led to the consideration of discontinuing treatments in thousands of patients. More recent experimental and clinical data indicate that ACEIs and, particularly, ARBs can be beneficial for COVID-19 outcome, both by reducing inflammatory responses and by triggering mechanisms (such as ADAM17 inhibition) counteracting viral entry. Strategies directly activating RAS anti-inflammatory components such as soluble ACE2, Angiotensin 1-7 analogues, and Mas or AT2 receptor agonists may also be beneficial. However, while ACEIs and ARBs are cheap and widely used, the second type of strategies are currently under study.

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Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Leal

Chen

et al. 2021

COVID

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Ibuprofen is a common over-the-counter drug taken for pain relief. However, recent studies have raised concerns about its potential toxic effect with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been proposed that ibuprofen may increase levels of angiotensin-converting enzyme 2 (ACE2), the human receptor for SARS-CoV-2 infection. Therefore, paracetamol is suggested as an alternative to ibuprofen for treating COVID-19 symptoms. Nevertheless, the relationship between intake of paracetamol or ibuprofen and either susceptibility to infection by SARS-CoV-2 or modulation of cellular ACE2 levels remains unclear. In this study, we combined data from human medical records and cells in culture to explore the role of the intake of these drugs in COVID-19. Although ibuprofen did not influence COVID-19 infectivity or ACE2 levels, paracetamol intake was associated with a lower occurrence of COVID-19 in our cohort. We also found that paracetamol led to decreased ACE2 protein levels in cultured cells. Our work identifies a putative protective effect of paracetamol against SARS-CoV-2 infection. Future work should explore the molecular mechanisms underlying the relationship between paracetamol and COVID-19.

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Adverse Outcomes and Mortality in Users of Non-Steroidal Anti-Inflammatory Drugs tested positive for SARS-CoV-2: A Danish Nationwide Cohort Study

Cited by 7 publications

References 28 publications

Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID‐19

Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID‐19

Drugs Modulating Renin-Angiotensin System in COVID-19 Treatment

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

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