Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19

Bruce, Eilidh; Barlow-Pay, Fenella; Short, Roxanna; Vilches‐Moraga, Arturo; Price, Angeline; McGovern, Aine; Braude, Philip; Stechman, Michael; Moug, Susan; McCarthy, Kathryn; Hewitt, Jonathan; Carter, Ben; Myint, Phyo Kyaw

doi:10.3390/jcm9082586

Cited by 52 publications

(56 citation statements)

References 22 publications

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“… 40 Although clinical implications of these in vivo findings caused confusion and trepidation in early stages of the COVID-19 pandemic, recent data from patients with COVID-19 show that non-steroidal anti-inflammatory drugs use is not associated with 30-day mortality, hospitalization, intensive care unit admission, mechanical ventilation, or renal replacement therapy in patients with COVID-19. 12 , 50 Similarly, a systematic review found that ACE inhibitors or angiotensin II type-I receptor blockers use was not associated with an increased severity of COVID-19 illness. 51 …”

Section: Sars-cov-2 Neurotropism and Its Implications For Pain Andmentioning

confidence: 99%

Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain

McFarland

Yousuf

Shiers

et al. 2021

PR9

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SARS-CoV-2 is a novel coronavirus that infects cells through the angiotensin-converting enzyme 2 receptor, aided by proteases that prime the spike protein of the virus to enhance cellular entry. Neuropilin 1 and 2 (NRP1 and NRP2) act as additional viral entry factors. SARS-CoV-2 infection causes COVID-19 disease. There is now strong evidence for neurological impacts of COVID-19, with pain as an important symptom, both in the acute phase of the disease and at later stages that are colloquially referred to as "long COVID." In this narrative review, we discuss how COVID-19 may interact with the peripheral nervous system to cause pain in the early and late stages of the disease. We begin with a review of the state of the science on how viruses cause pain through direct and indirect interactions with nociceptors. We then cover what we currently know about how the unique cytokine profiles of moderate and severe COVID-19 may drive plasticity in nociceptors to promote pain and worsen existing pain states. Finally, we review evidence for direct infection of nociceptors by SARS-CoV-2 and the implications of this potential neurotropism. The state of the science points to multiple potential mechanisms through which COVID-19 could induce changes in nociceptor excitability that would be expected to promote pain, induce neuropathies, and worsen existing pain states.

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Section: Sars-cov-2 Neurotropism and Its Implications For Pain Andmentioning

confidence: 99%

Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain

McFarland

Yousuf

Shiers

et al. 2021

PR9

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“…Several studies are accumulating and reappraising the importance of NSAIDs in COVID-19 management (Bruce et al, 2020;Kutti Sridharan et al, 2020;Smart and Fawkes, 2020;Zolk et al, 2020); interestingly two in silico screenings independently identified the COX-II inhibitor celecoxib as a potential anti-SARS-CoV-2 drug, and a very recent study still under peer review reports its beneficial effects plus famotidine in hospitalized patients (Tomera et al, 2020).…”

Section: Nsaids Paracetamol and Covid-19mentioning

confidence: 99%

“…On the other hand, the warning was immediately questioned ( Moore et al., 2020 ; Rothuizen et al., 2020 ) and few months later a study on the association between routine use of NSAIDs and outcomes in hospitalized COVID-19 patients drawn completely different conclusions ( Bruce et al., 2020 ).…”

Section: Nsaids Paracetamol and Covid-19mentioning

confidence: 99%

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

Sestili

Fimognari

2020

Front. Pharmacol.

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COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and hostdirected medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.

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“…The bases for that warning mostly relied on anecdotal reports and non-peer-reviewed expert opinions, which went on to speculate that patients may be more vulnerable to SARS-CoV-2 infection if take drugs with proposed ability to increase ACE-2 expression, such as ACE inhibitors, Ang II receptor blockers and ibuprofen [ 57 , 84 ]. Soon after, numerous other global authorities urged prudence and several reports stressed the need for further evidence to get a clearer picture [ 85 , 86 , 87 , 88 , 89 , 90 ]. To this end, four registered trials are currently investigating the impact of ibuprofen (NCT04383899; NCT04334629; NCT04382768) and of naproxen (NCT04325633) on COVID-19 disease.…”

Section: Nsaid Use During Covid-19 Pandemic: Pros and Consmentioning

confidence: 99%

“…In severe cases of COVID-19, ARDS is often associated with the development of a cytokine release syndrome. In this framework, a NSAID-dependent COX inhibition may reduce the recruitment of polymorphonuclear cells (in particular neutrophils) that during the course of inflammation eventually change the profile of lipid mediators produced toward synthesis of SPM metabolites [ 85 , 96 , 99 , 100 , 101 ]. Another potential issue to consider is that the anti-inflammatory and antipyretic effects of NSAIDs and acetaminophen may mask the early symptoms of infection and thus delay diagnosis and rapid management of the affected patients [ 56 , 57 ].…”

Section: Nsaid Use During Covid-19 Pandemic: Pros and Consmentioning

confidence: 99%

Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review

Lariccia

Magi

Serfilippi

et al. 2020

JCM

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The novel coronavirus disease 2019 (COVID-19) is a global pandemic that continues to sweep across the world, posing an urgent need for effective therapies and prevention of the spread of the severe acute respiratory syndrome related to coronavirus-2 (SARS-CoV-2). A major hypothesis that is currently guiding research and clinical care posits that an excessive and uncontrolled surge of pro-inflammatory cytokines (the so-called “cytokine storm”) drives morbidity and mortality in the most severe cases. In the overall efforts made to develop effective and safe therapies (including vaccines) for COVID-19, clinicians are thus repurposing ready-to-use drugs with direct or indirect anti-inflammatory and immunomodulatory activities. Speculatively, there are many opportunities and challenges in targeting immune/inflammatory processes in the evolving settings of COVID-19 disease because of the need to safely balance the fight against virus and aggressive inflammation versus the suppression of host immune defenses and the risk of additional harms in already compromised patients. To this end, many studies are globally underway to weigh the pros and cons of tailoring drugs used for inflammatory-driven conditions to COVID-19 patient care, and the next step will be to summarize the growing clinical trial experience into clean clinical practice. Based on the current evidence, anti-inflammatory drugs should be considered as complementary approaches to anti-viral drugs that need to be timely introduced in the management of COVID-19 according to disease severity. While drugs that target SARS-CoV-2 entry or replication are expected to confer the greatest benefits at the early stage of the infection, anti-inflammatory drugs would be more effective in limiting the inflammatory processes that drive the worsening of the disease.

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Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19

Cited by 52 publications

References 22 publications

Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain

Neurobiology of SARS-CoV-2 interactions with the peripheral nervous system: implications for COVID-19 and pain

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review

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