Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea

  1. Kyungmin Huh
  2. Wonjun Ji
  3. Minsun Kang
  4. Jinwook Hong
  5. Gi Hwan Bae
  6. Rugyeom Lee
  7. Yewon Na
  8. Hyoseon Choi
  9. Seon Yeong Gong
  10. Jaehun Jung

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Abstract

Background

Identifying the association between medications taken prior to the infection of coronavirus disease (COVID-19) might be useful during the current pandemic until a proven treatment is developed. We aimed to determine whether the risk of developing COVID-19 was associated with the use of various drugs that may increase or decrease susceptibility to severe acute respiratory syndrome coronavirus 2 infection and COVID-19.

Methods and Findings

A case-control study was performed using a nationwide claims database of South Korea, where a large testing capacity has been available throughout the pandemic. Exposure was defined as the prescription of study drugs that would have been continued until ≤7 days before the testing for COVID-19. Adults were considered eligible if they were ≥18 years old and tested for COVID-19. Among the 65,149 eligible subjects (mean age, 48.3 years; 49.4% male), 5,172 (7.9%) were diagnosed with COVID-19. Hydroxychloroquine was not significantly associated with the risk of COVID-19 (adjusted odds ratio [aOR], 1.48; 95% CI, 0.95–2.31). In the overall population, lower risks of COVID-19 were associated with the use of camostat (aOR, 0.45; 95% CI, 0.20–1.02) and amiodarone (aOR, 0.54; 95% CI, 0.33–0.89), although the differences were not significant in the subgroup analyses. Angiotensin receptor blockers were also associated with a slightly increased risk of COVID-19 (aOR, 1.13; 95% CI, 1.01–1.26), which was also not observed in the subgroup analysis. The study limitations include potential bias regarding the controls’ characteristics, inability to determine prescription compliance, and a lack of information regarding the severity of underlying conditions.

Conclusions

No medications were consistently associated with increased or decreased risks of COVID-19. These findings suggest that a more cautious approach is warranted for the clinical use of re-purposed drugs until the results are available from clinical trials.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.04.20089904: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study’s retrospective protocol was approved by the institutional review board of the Gil Medical Center, Gachon University College of Medicine and Science (GFIRB2020-118).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All analyses were performed using SAS software (version 9.4; SAS Institute Inc., Cary, NC, USA).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    The present study also has several limitations. First, our design was vulnerable to bias in the characteristics of “test-negative” controls. Controls were older and had more comorbidities in our study, and we suspect that older people with underlying conditions had higher chance of developing acute respiratory symptoms which led to vigorous testing. However, we conducted robust multivariable analyses and a subgroup analysis on DG area where the risk of community transmission was substantially higher. Second, the use of claims data precludes an analysis of prescription compliance or the accuracy of comorbidity diagnoses. Third, we could not obtain data regarding the severity of the underlying conditions, performance status, and socioeconomic characteristics. Last, some drugs were prescribed infrequently and the small sample sizes limited the statistical power of the related analyses. In conclusion, we observed that no medications were consistently associated with the risk for COVID-19. Camostat and amiodarone might be associated with lower risk, which warrants further studies. However, the use of HCQ, ACEIs/ARBs, or statins was not associated with a significant change in the risk of COVID-19. Our findings suggest that repurposing these pharmaceutical agents may not provide significant clinical benefits for the patients with COVID-19. Clinical trials are needed to generate high-quality evidence regarding the efficacy of these agents in this setting.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.05.04.20089904 on medRxiv