Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study

  1. Han Eol Jeong
  2. Hyesung Lee
  3. Hyun Joon Shin
  4. Young June Choe
  5. Kristian B Filion
  6. Ju-Young Shin

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Abstract

Background

Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells.

Methods

We conducted a cohort study using South Korea’s nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding.

Results

Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14).

Conclusions

While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.

Article activity feed

  1. Version published to 10.1093/cid/ciaa1056
  2. Version published to 10.1101/2020.06.01.20119768v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.06.01.20119768: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: 14 This study was approved by the Institutional Review Board of Sungkyunkwan University (SKKU 2020-03-012), which waived the requirement of obtaining informed consent.
    Consent: 14 This study was approved by the Institutional Review Board of Sungkyunkwan University (SKKU 2020-03-012), which waived the requirement of obtaining informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Use of co-medications were defined using ATC codes and included the following medications: angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor II blockers (ARBs), β-blockers, calcium channel blockers, diuretics, and nitrates (Supplementary Material 2).
    ATC
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, given the limitations of pharmacovigilance assessments, causality could not be assessed. Moreover, a systematic review of observational studies found an increased risk of pleuropulmonary complications, disseminated infection, abscess, prolonged illness, delays in antibiotic prescriptions associated with NSAIDs in patients with community-acquired pneumonia.21,22 It is possible that NSAIDs use could have similarly worsened outcomes from SARS-CoV-2 pneumonia. Our findings showed a particularly increased risk of cardiovascular or renal complications among NSAIDs users (IPTW OR 1·87, 95% CI 1·25-2·80) compared to non-users. This finding is consistent to the results of two case-crossover studies conducted among patients with acute respiratory infections, which found that NSAIDs use, as compared with non-use, was associated with increased risks of ischemic stroke (aOR 2·27, 95% CI 2·00-2·58) and myocardial infarction (aOR 3·41, 95% CI 2·80-4·16).23,24 In addition to the established risks of myocardial infarction and stroke associated with NSAIDs use in the general population,25,26 our findings suggest an elevated risk of cardiovascular complications with NSAIDs use in COVID-19 patients. Moreover, use of NSAIDs that results in nephrotoxicity27,28 may be more common among those seriously affected by COVID-19, as health conditions could be further exacerbated by fever and dehydration. The underlying pathogenic link between NSAIDs and COVID-19 has yet to be elucidated. However,...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  4. Version published to 10.1101/2020.06.01.20119768v1 on medRxiv