NSAID use not tied to increased COVID-19 severity

The use of non-steroidal anti-inflammatory drugs (NSAIDs) prior to hospitalization for COVID-19 does not increase the risk of severe COVID-19 outcomes including mortality and requirement for ventilation or supplemental oxygen, according to findings from the ISARIC-CCP-UK* prospective cohort study.

“[This study] found that in patients who were admitted to hospital with COVID-19, those taking NSAIDs before admission had the same outcomes as those who did not,” the authors noted. “NSAIDs do not appear to increase the risk of worse in-hospital outcomes,” they stressed.

Participants were 72,179 individuals of any age (56.2 percent male) hospitalized with a RT-PCR confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between January 17 and August 10, 2020, at 255 healthcare facilities in England, Scotland, and Wales. Of these, 5.8 percent (n=4,211) had documented systemic NSAID use (excluding aspirin) 2 weeks prior to hospitalization. Patients were followed up throughout hospitalization duration.

There was no significant difference in disease severity between patients with and without NSAID use at hospital admission. Quick Sequential Organ Failure Assessment scores at admission were similar between NSAID users and non-users (mean difference, -0.02; p=0.42), as were National Early Warning Score 2 scores (mean difference, -0.08; p=0.46).

Use of NSAIDs was not associated with an increased risk of in-hospital mortality compared with non-use (matched odds ratio [OR], 0.95, 95 percent confidence interval [CI], 0.84–1.07; p=0.35). [Lancet Rheumatol 2021;3:e498-e506]

The results were consistent when the analysis was limited to patients admitted ≥7 days after symptom onset (OR, 1.11; p=0.37) or those with rheumatological disease (OR, 0.90; p=0.44).

NSAID type did not affect the mortality outcome. Ibuprofen, the most frequently used NSAID in this study, was not associated with a higher mortality risk compared with NSAID non-use (OR, 0.90; p=0.36) or use of other NSAIDs (OR, 0.82; p=0.082).

There was also no significant association between NSAID use and increased risk of admission to critical care (OR, 1.01, 95 percent CI, 0.87–1.17; p=0.89), requirement for either invasive (OR, 0.96, 95 percent CI, 0.80–1.17; p=0.69) or non-invasive ventilation (OR, 1.12, 95 percent CI, 0.96–1.32; p=0.14), requirement for supplementary oxygen (OR, 1.00, 95 percent CI, 0.89–1.12; p=0.97), or incidence of acute kidney injury (OR, 1.08, 95 percent CI, 0.92–1.26; p=0.33).

“NSAIDs are commonly used to treat people … for a range of conditions, from minor aches and pains to chronic conditions such as arthritis and cardiovascular disease. Many people rely on them to be able to carry out their day-to-day activities,” said lead author Professor Ewen Harrison, of the University of Edinburgh, Edinburgh, UK.

According to the authors, unpublished data in the early stage of the COVID-19 pandemic raised questions on the possible impact of NSAID use on the severity of COVID-19. [BMJ 2020;368:m1086]

“When the pandemic began over a year ago, we needed to be sure that these common medications would not lead to worse outcomes in people with COVID-19. We now have clear evidence that NSAIDs are safe to use in patients with COVID-19, which should provide reassurance to both clinicians and patients that they can continue to be used in the same way as before the pandemic began,” Harrison said.

The authors noted that the cohort did not include non-hospitalized COVID-19 patients or those who died before hospitalization. They also acknowledged the lack of data on the indications for the specific NSAIDs, dosages, adherence, and duration of use, including whether NSAIDs were continued during hospitalization.

“[I]t is unclear whether a potential harmful effect of NSAIDs is masked by discontinuation during hospital stay, low dosages, or short treatment duration,” said Dr Kristian Kragholm from Aalborg University Hospital, Aalborg, Denmark, and co-authors in an accompanying commentary. [Lancet Rheumatol 2021;9:e465-e466]

“This study also did not provide any insight into whether comparator drugs (ie, paracetamol) were better, equal, or worse in terms of COVID-19 outcomes,” they added.

These limitations should be addressed in future research, said the study authors.