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. 2020 Sep 8;17(9):e1003308.
doi: 10.1371/journal.pmed.1003308. eCollection 2020 Sep.

Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study

Lars Christian Lund  1 , Kasper Bruun Kristensen  1 , Mette Reilev  1 , Steffen Christensen  2 , Reimar Wernich Thomsen  3 , Christian Fynbo Christiansen  3 , Henrik Støvring  1   4 , Nanna Borup Johansen  5 , Nikolai Constantin Brun  5 , Jesper Hallas  1 , Anton Pottegård  1
Affiliations

Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study

Lars Christian Lund et al. PLoS Med. .

Abstract

Background: Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.

Methods and findings: We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI -3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI -3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI -3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI -2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD -0.2%, 95% CI -2.0% to 1.6%, p = 0.81). The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.

Conclusions: Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.

Trial registration: The European Union electronic Register of Post-Authorisation Studies EUPAS34734.

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Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: KBK, NBJ, SC, NB, declare no conflicts of interest. RWT and CFC declare no personal conflicts of interest, yet the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study. HS reports personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from Roche, outside the submitted work. AP and JH report participation in research funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Servier and LEO Pharma, all with funds paid to the institution where they were employed (no personal fees) and with no relation to the work reported in this paper. LCL reports participation in research projects funded by Menarini Pharmaceutical and LEO Pharma, with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this paper. MR reports participation in research projects funded by LEO Pharma, with funds paid to the institution where she was employed (no personal fees) and with no relation to the work reported in this paper.

Figures

Fig 1
Fig 1. Study design diagram.
NSAID, non-steroidal anti-inflammatory drug; RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
See this image and copyright information in PMC

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