COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Etiology Wong AY, MacKenna B, Morton CE, et al. Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts. Ann Rheum Dis. 2021 Jan 21. pii: annrheumdis-2020-219517. doi: 10.1136/annrheumdis-2020-219517.

OBJECTIVES: To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.

METHODS: We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region.

RESULTS: In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use.

CONCLUSIONS: We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

Discipline / Specialty Area Score
Family Medicine (FM)/General Practice (GP)
Emergency Medicine
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Intensivist/Critical Care
Comments from MORE raters

Emergency Medicine rater

Chronic and acute analgesia in the midst of an opioid epidemic and global COVID-19 pandemic already challenges effective transitions of care to mitigate oligoanalgesia ( This analysis of nearly 1.5 million patients strongly indicates that NSAIDs need not be avoided out of concern for increased COVID-19-related mortality.

Emergency Medicine rater

Although this was not a randomized trial, this study will make clinicians more comfortable recommending NSAIDs for Covid symptoms.

Family Medicine (FM)/General Practice (GP) rater

There were two study populations in England: 1) 2,463,707 people who ever used NSAIDs in the past 3 years from the general population; and 2) 1,708,781 people with rheumatoid arthritis / osteoarthritis. Comparing users and non-users in each group revealed no association between NSAIDs and COVID-19 related death.

Family Medicine (FM)/General Practice (GP) rater

Negative study results such as this regarding the safety of NSAIDs in Covid are extremely important for patient and treating clinician confidence in continuing necessary medications. Previous smaller studies suggested the safety of continuing NSAIDs, but many doctors may not know that this large and well conducted study clearly supported earlier suggestions of safety.

Infectious Disease rater

This study used a large retrospective database to provide reassuring data on the lack of adverse effects of NSAIDs in COVID-19 infection.

Rheumatology rater

This is quite reassuring information for many practitioners managing patients with rheumatic diseases. Although this information was expected because of prior studies, having a largely confirmatory study of this magnitude with sound methodology is very useful.