The impact of NSAIDs on COVID-19 severity

By Colin Lightfoot, M.Sc. Infection and ImmunityReviewed by Benedette Cuffari, M.Sc.May 18 2022

Since its emergence in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 525 million people and caused more than 6.28 million deaths globally. SARS-CoV-2 infection results in the coronavirus disease 2019 (COVID-19), which is characterized by a wide range of symptoms, with serious effects including pneumonia and hypoxemic respiratory failure.

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Study: NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study. Image Credit: piggu / Shutterstock.com

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) primarily block cyclooxygenase (COX), which is an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The widespread use of NSAIDs causes these medications to often be associated with significant side effects that necessitate hospitalization.

Recent studies have indicated that NSAID treatment decreased both antibody and proinflammatory cytokine responses to SARS-CoV-2 infection in a mouse model of COVID-19. Despite these observations, the timing of NSAID exposure appears to be time-dependent.

Early NSAID treatment, for example, may have a deleterious impact on the initial antiviral immune response in COVID-19. Comparatively, NSAID treatment later on in the infection may reduce immunological-driven pathologies such as the cytokine storm; however, there is little data to support this hypothesis.

About the study

In a recent Virology Journal study, researchers utilized data from the National COVID Cohort Collaborative (N3C) to examine potential correlations of NSAID use in a large, multi-center database. A total of twelve NSAIDs that had been previously tested in a smaller cohort were evaluated for their impact on COVID-19 severity.

N3C collects electronic health record (EHR) data from 66 clinical organizations across the United States. Patient records from the 38 locations that provided data for all factors used in the regression analysis were extracted for this study.

N3C also provides phenotype descriptions that are shared across organizations, such as positive COVID-19 laboratory tests and COVID-19 medical severity classifications. Since previous analyses revealed that NSAID use among outpatients was likely incompletely recorded, the current study focused on inpatients receiving NSAID treatment.

Study findings

In a retrospective study, 857,061 patients with COVID-19 were analyzed, which included twelve NSAIDs that were examined previously in a smaller population. SARS-CoV-2-positive patients were then separated into two groups, which included those who were given an NSAID when they were admitted (treated) and those who did not receive NSAID treatment (controls).

Propensity matching was used to compare NSAID-treated and control patients based on various demographics including age, race, body mass index (BMI), and the existence of 24 comorbidities before COVID-19 presentation to limit the effect of ambiguity.

The investigation consisted of 66,494 SARS-CoV-2-positive patients who had complete data and were not using aspirin or acetaminophen. A total of 19,746 individuals were given an NSAID during the 24 hours leading up to admission and were included in the test group, while the same number of patients who were not on NSAIDs were chosen using propensity matching. For all variables, the standard mean difference between NSAID-treated and control groups was less than 0.1 after propensity matching.

COVID-19 severity, which was described as either moderate or severe, as well as mortality/hospice, were the primary outcomes in this study. The NSAID group showed an increased rate of moderate COVID-19 as compared to the control cohort; however, the NSAID cohort had a lower risk of severe COVID-19 as compared to those with moderate disease. When controlling for patient demographics, a significant association was observed between NSAID use and decreased COVID-19 severity.

The association between NSAID use and secondary outcomes including acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality was also investigated at any time after COVID-19 diagnosis using logistic regression. Death, invasive ventilation, AKI, and ECMO were all considerably reduced when NSAIDs were used.

Implications

In COVID-19 inpatients, NSAID use is not associated with greater COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO. In fact, the current study found that NSAID use instead reduced the risk of these outcomes in COVID-19 patients. Taken together, the findings from the current study provide additional evidence that NSAID use is not associated with any detrimental effects on hospitalized COVID-19 patients.