No link between NSAIDs, more severe COVID-19
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There is no association between the use of NSAIDs and increased COVID-19 severity or mortality, according to data published in The Lancet Rheumatology.
“Studies of patients with non-SARS-CoV-2 respiratory infection have found associations between NSAID (including cyclooxygenase [COX]-2 inhibitors) use and increased rates of complications,” Thomas M. Drake, MBChB, of the University of Edinburgh’s Usher Institute, in the United Kingdom, and colleagues wrote. “These studies found that NSAID use was associated with higher rates of myocardial infarction, pleural empyema and longer length of hospital stay. However, outcomes used in such pneumonia studies, for example empyema, are less frequent in patients with SARS-CoV-2 infection.”
“In preclinical models, there is evidence that NSAIDs decrease pulmonary edema, lessen endothelial leakiness, and reduce the severity of acute respiratory distress syndrome (ARDS), leading to the suggestion they might be useful in the treatment of COVID-19, with at least one clinical trial currently underway,” they added.
To analyze whether NSAID use is associated with increased COVID-19 severity, Drake and colleagues conducted a prospective, multicenter cohort study of 78,674 patients across 255 health care facilities in England, Scotland and Wales. Participants included patients of any age who were hospitalized with confirmed or highly suspected SARS-CoV-2 infection, leading to COVID-19, between Jan. 17, 2020, and Aug. 10, 2020. In all, 72,179 patients had death outcomes available for matching. Among this group, 4,211 were recorded as taking systemic NSAIDs prior to hospitalization.
The primary outcome was in-hospital mortality, while secondary outcomes included disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. The researchers used logistic regression to estimate the effects of NSAIDs, adjusting for confounding variables, as well as propensity score matching to further estimate their effects, accounting for covariate differences in populations.
After propensity score matching, Drake and colleagues established two balanced groups of NSAID users and non-users, each with 4,205 patients, for comparison.
According to the researchers, there were no significant differences in severity between the two groups at hospitalization. After adjusting for explanatory variables, there was no association between NSAID use and worse in-hospital mortality (matched OR = 0.95; 95% CI, 0.84-1.07), critical care admission (matched OR = 1.01; 95% CI, 0.87-1.17), requirement for invasive ventilation (matched OR = 0.96; 95% CI, 0.80-1.17), requirement for non-invasive ventilation (matched OR = 1.12; 95% CI, 0.96-1.32), requirement for oxygen (matched OR = 1; 95% CI, 0.89-1.12), or acute kidney injury (matched OR = 1.08; 95% CI, 0.92-1.26).
“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,” Drake and colleagues wrote. “Our study did not capture whether NSAIDs were continued in hospital, so we cannot make any recommendations on whether these should be withheld or continued after hospital admission.
“There are important groups of patients who rely on NSAIDs for pain relief, including those with inflammatory joint diseases, bone pain, gout, postoperative pain and menstrual pain, who would otherwise have few non-opioid options for pain relief,” they added. “Taken together, clinicians should continue to prescribe and manage NSAIDs in the same way as before the COVID-19 pandemic began.”
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