J Korean Med Sci.  2023 Sep;38(36):e280. 10.3346/jkms.2023.38.e280.

Risk Factors for the Prescription of Ineffective Antiviral Candidates for COVID-19 During the Early Pandemic Period in Korea

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 2Division of Infectious Diseases, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
  • 3Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Korea
  • 4College of Pharmacy, Dankook University, Cheonan, Korea
  • 5Public Healthcare Center, Seoul National University Hospital, Seoul, Korea
  • 6Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 7Department of Medicine, Seoul National University College of Medicine, Seoul, Korea

Abstract

Background
Although the evidence of treatment for coronavirus disease 2019 (COVID-19) changed rapidly, little is known about the patterns of potential pharmacological treatment during the early period of the COVID-19 pandemic in Korea and the risk factors for ineffective prescription.
Methods
Using claims data from the Korean National Health Insurance System, this retrospective cohort study included admission episodes for COVID-19 from February to December 2020. Ineffective antiviral prescriptions for COVID-19 were defined as lopinavir/ ritonavir (LPN/r) and hydroxychloroquine (HCQ) prescribed after July 2020, according to the revised National Institute of Health COVID-19 treatment guidelines. Factors associated with ineffective prescriptions, including patient and hospital factors, were identified by multivariate logistic regression analysis.
Results
Of the 15,723 COVID-19 admission episodes from February to June 2020, 4,183 (26.6%) included prescriptions of LPN/r, and 3,312 (21.1%) included prescriptions of HCQ. Of the 48,843 admission episodes from July to December 2020, after the guidelines were revised, 2,258 (4.6%) and 182 (0.4%) included prescriptions of ineffective LPN/r and HCQ, respectively. Patient factors independently associated with ineffective antiviral prescription were older age (adjusted odds ratio [aOR] per 10-year increase, 1.17; 95% confidence interval [CI], 1.14–1.20) and severe condition with an oxygen requirement (aOR, 2.49; 95% CI, 2.24–2.77). The prescription of ineffective antiviral drugs was highly prevalent in primary and nursing hospitals (aOR, 40.58; 95% CI, 31.97–51.50), public sector hospitals (aOR, 15.61; 95% CI, 12.76–19.09), and regions in which these drugs were highly prescribed before July 2020 (aOR, 10.65; 95% CI, 8.26–13.74).
Conclusion
Ineffective antiviral agents were prescribed to a substantial number of patients during the first year of the COVID-19 pandemic in Korea. Treatment with these ineffective drugs tended to be prolonged in severely ill patients and in primary and public hospitals.

Keyword

Emerging Infectious Disease; Pandemics; Disaster Medicine; COVID-19; Hydroxychloroquine; Lopinavir/Ritonavir

Figure

  • Fig. 1 Chronological presentation of the prescription of candidate antiviral agents and corticosteroids for coronavirus disease 2019 treatment in Korea according to disease severity. (A) All patients, (B) patients who received oxygen therapy.


Reference

1. Kim ES, Chin BS, Kang CK, Kim NJ, Kang YM, Choi JP, et al. Clinical course and outcomes of patients with severe acute respiratory syndrome coronavirus 2 infection: a preliminary report of the first 28 patients from the Korean cohort study on COVID-19. J Korean Med Sci. 2020; 35(13):e142. PMID: 32242348.
Article
2. Suh HJ, Kim DH, Heo EY, Lee HW, Lee JK, Lee CS, et al. Clinical characteristics of COVID-19: clinical dynamics of mild severe acute respiratory syndrome coronavirus 2 infection detected by early active surveillance. J Korean Med Sci. 2020; 35(32):e297. PMID: 32808513.
Article
3. Kim PS, Read SW, Fauci AS. Therapy for early COVID-19: a critical need. JAMA. 2020; 324(21):2149–2150. PMID: 33175121.
4. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, January 28, 2020. Accessed April 25, 2023. https://apps.who.int/iris/handle/10665/330893 .
5. World Health Organization. Therapeutics and COVID-19: living guideline, November 20, 2020. Accessed April 25, 2023. https://apps.who.int/iris/handle/10665/336729 .
6. National Institutes of Health COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. April 21, 2020. Accessed April 25, 2023. https://www.covid19treatmentguidelines.nih.gov/ .
7. The National Institute for Health and Care Excellence (NICE) guideline: COVID-19 rapid guideline: managing COVID-19, March 23, 2021. Accessed April 25, 2023. https://www.nice.org.uk/guidance/ng191 .
8. Jeon J, Chin B. Treatment options for patients with mild-to-moderate coronavirus disease 2019 in Korea. J Korean Med Sci. 2022; 37(48):e352. PMID: 36513054.
Article
9. Park DH, Kang CK, Choe PG, Kim NJ, Park WB, Oh MD. How we have treated severe to critically ill patients with coronavirus disease 2019 in Korea. J Korean Med Sci. 2022; 37(49):e353. PMID: 36536547.
Article
10. WHO Solidarity Trial Consortium. Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al. Repurposed antiviral drugs for Covid-19 - interim WHO solidarity trial results. N Engl J Med. 2021; 384(6):497–511. PMID: 33264556.
Article
11. FDA News Release. Coronavirus (COVID-19) update: FDA revokes emergency use authorization for chloroquine and hydroxychloroquine, June 15, 2020. Accessed April 25, 2023. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and#:~:text=Today%2C%20the%20U.S.%20Food%20and,clinical%20trial%20was%20unavailable%2C%20or .
12. Kang CK, Seong MW, Choi SJ, Kim TS, Choe PG, Song SH, et al. In vitro activity of lopinavir/ritonavir and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 at concentrations achievable by usual doses. Korean J Intern Med. 2020; 35(4):782–787. PMID: 32460458.
Article
13. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020; 382(19):1787–1799. PMID: 32187464.
14. Riva L, Yuan S, Yin X, Martin-Sancho L, Matsunaga N, Pache L, et al. Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature. 2020; 586(7827):113–119. PMID: 32707573.
Article
15. Weston S, Coleman CM, Haupt R, Logue J, Matthews K, Li Y, et al. Broad anti-coronavirus activity of food and drug administration-approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo. J Virol. 2020; 94(21):e01218-20. PMID: 32817221.
Article
16. Berendes S, Heywood P, Oliver S, Garner P. Quality of private and public ambulatory health care in low and middle income countries: systematic review of comparative studies. PLoS Med. 2011; 8(4):e1000433. PMID: 21532746.
Article
17. Basu S, Andrews J, Kishore S, Panjabi R, Stuckler D. Comparative performance of private and public healthcare systems in low- and middle-income countries: a systematic review. PLoS Med. 2012; 9(6):e1001244. PMID: 22723748.
Article
18. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020; 395(10223):473–475. PMID: 32043983.
19. Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020; 395(10225):683–684. PMID: 32122468.
Article
20. RECOVERY Collaborative Group. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021; 384(8):693–704. PMID: 32678530.
Article
21. World Health Organization. Therapeutics and COVID-19: living guideline. September 2, 2020. Accessed April 25, 2023. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.4 .
22. The National Institutes of Health COVID-19 Treatment Guidelines Panel provides recommendations for dexamethasone in patients with COVID-19. Updated June 25, 2020. Accessed April 25, 2023. https://files.covid19treatmentguidelines.nih.gov/guidelines/archive/recommendations-for-dexametha-06-25-2020.pdf .
23. Watanabe JH, Kwon J, Nan B, Abeles SR, Jia S, Mehta SR. Medication use patterns in hospitalized patients with COVID-19 in California during the pandemic. JAMA Netw Open. 2021; 4(5):e2110775. PMID: 34019090.
24. Nori P, Bartash R, Cowman K, Dackis M, Pirofski LA. Is burnout infectious? Understanding drivers of burnout and job satisfaction among academic infectious diseases physicians. Open Forum Infect Dis. 2019; 6(4):ofz092. PMID: 31041336.
Article
25. Lugtenberg M, Zegers-van Schaick JM, Westert GP, Burgers JS. Why don’t physicians adhere to guideline recommendations in practice? An analysis of barriers among Dutch general practitioners. Implement Sci. 2009; 4(1):54. PMID: 19674440.
Article
26. Lugtenberg M, Burgers JS, Han D, Westert GP. General practitioners’ preferences for interventions to improve guideline adherence. J Eval Clin Pract. 2014; 20(6):820–826. PMID: 24953439.
Article
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr