No Link Found Between Non-Steroidal Anti-Inflammatory Treatment and Severe COVID-19 Outcomes

Professor Ewen M. Harrison

During the early months of the COVID-19 pandemic, the preexisting use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, was thought to increase disease severity in patients with COVID-19.

Investigators, led by Prof Ewen M Harrison, Centre for Medical Informatics, Usher Institute, University of Edinburgh, conducted a prospective, multi-center cohort study and found that the use of NSAIDs were not associated with higher mortality or increased severity of COVID-19.

Study

The goal of the study was to characterize the safety of NSAIDs, while identifying if pre-existing NSAIDs use was associated with an increased severity of COVID-19.

Investigators used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Clinical Characterization Protocol (CCP) for Severe Emerging Infection in the study, which was activated for COVID-19 in January 2020.

Eligibility for the study included patients of any age admitted to the hospital with a confirmed or highly suspected SARS-CoV-2 Infection leading to COVID-19 between January – August 2020.

Data on admission, hospital stay, and discharge were collected, as well as demographic data including age, sex, and comorbidities. Information on current NSAIDs medication or medication taken within the past 2 weeks from the study were also collected.

The primary outcome included in-hospital morality, while the secondary outcomes were admission to critical care, use of invasive mechanical ventilation, use of non-invasive ventilation, use of supplementary oxygen, and occurrence of acute kidney injury.

Logistic regression estimated the effects of NSAIDs and adjusted for confounding variables. Investigators also used propensity score matching to estimate the treatment effect of NSAIDs and accounted for covariate differences in the populations.

Results

The study included 78,674 patients enrolled 255 healthcare facilities in the United Kingdom between January – August 2020. The patient population represented 60% of the total people admitted to the hospital with COVID-19.

Of the patients, 72,179 had death outcomes for matching. Demographics included 38,151 male (56.1%) and 29,564 (43.5%) female patients.

The study cohort included 4211 (5.8%) patients recorded as taking systemic NSAIDs before they were admitted to hospital. Propensity score matching created balanced groups of NSAIDs users and non-NSAIDs users, with 4205 patients in each group.

Investigators found 1279 (30.4%) of 4211 patients in the NSAIDs group died versus 21 256 (31.3%) of 67,698 patients in the non-NSAIDs group.

After matching, the team found NSAIDs use was not associated with worse in-hospital mortality with an odds ratio (OR) of 0.95 (95% CI, 0.84 – 1.07, P = 0.35).

Patients taking NSADS were also not more likely to require critical care admission, (OR 1.01; 95% CI, 0.81 – 1.17; P = .89), invasive ventilation (OR 0.96; 95% CI, 0.80 – 1.17; P = .69), or non-invasive ventilation (OR 1.12; 95% CI, 0.96 – 1.32); P = 0.14), compared to those not taking NSAIDs.

Investigators also found they were not more likely to require supplementary oxygen (OR 1.00; 95% CI, 0.89 – 1.12; P = 0.97) or sustain acute kidney injury (OR 1.08; 95% CI, 0.92 – 1.26; P = 0.33) compared to those not taking NSAIDs.

The use of ibuprofen was not associated with increased mortality compared with those not taking any NSAIDs (OR 0.90; 95% CI, 0.71 – 1.13; P = .36) or those taking other NSAIDs (OR 0.82; 95% CI, 0.66 – 1.03; P = .082).

Conclusion

Investigators concluded that patients admitted to the hospital with COVID-19 and were also taking NSAIDs did not have more severe disease than those not taking NSAIDs.

“For clinicians and patients, our findings should provide reassurance that NSAIDs can be used as indicated in the community without increasing the severity of COVID-19,” investigators wrote.

The study, “Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study,” was published online in The Lancet Rheumatology.