Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study

Abstract

Background Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection. Methods and findings We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 nonusers on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI −3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts

“…A recent cohort study demonstrated that NSAIDs were not associated with 30-day mortality or other severe COVID-19 outcomes in Danish people who tested positive for SARS-CoV-2. 20 This study was well conducted with robust methodology and of large sample size but it might still be subject to potential issues around selective testing for COVID-19. Furthermore, specific types of NSAIDs were not explored in the analyses, limiting the interpretation of the results.…”

“… 18 19 One cohort study was recently conducted to investigate such association, but individual NSAIDs were not specifically investigated. 20 …”

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

“… 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 …”

Potential for increased prevalence of neuropathic pain after the COVID-19 pandemic

“… 46 Multiple concerns have been raised about the use of nonsteroidal anti-inflammatory agents in patients infected with SARS Co-2, but recent large-scale surveys seem to indicate that their use is not associated with significant increase in mortality, hospitalization, or ICU admission. 38 The mainstay of therapy for neuropathic pain is represented by gabapentinoids (gabapentin and pregabalin), antidepressants (serotonin and noradrenalin reuptake inhibitor antidepressants or tricyclic antidepressants), tramadol, and topical agents (lidocaine plasters, capsaicin high concentration patches or botulinum toxin A for peripheral neuropathic pain), while strong opioids may be considered in refractory cases. 19 , 47 However, these drugs have an overall modest therapeutic efficacy.…”