J Korean Med Sci.  2022 Aug;37(32):e252. 10.3346/jkms.2022.37.e252.

Breakthrough COVID-19 Infection During the Delta Variant Dominant Period: Individualized Care Based on Vaccination Status Is Needed

  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 2Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea
  • 3Division of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea


The clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon.
We retrospectively analyzed hospitalized COVID-19 patients during a delta variantdominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status.
A total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients.
In the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.


Breakthrough Infection; SARS-CoV-2; COVID-19; Severe Progression; Oxygen Therapy


  • Fig. 1 Study setting. A total of 438 patients were enrolled, 188 of whom were unvaccinated and 250 of whom were vaccinated. The vaccinated group was divided into the fully vaccinated group and the partially vaccinated group.

  • Fig. 2 Requirement for oxygen therapy at admission and during hospitalization among the unvaccinated (n = 188) and fully vaccinated groups (n = 133). The results are presented as the number of individuals in the UV group and the FV group. Among the 188 patients in UV group, 35 patients required oxygen at admission and 31 patients out of the other 153 patients (20.3%, 31/153) experienced clinical aggravation to need new oxygen requirement. Among the 133 patients in FV group, 13 patients required oxygen at admission and 13 patients out of the other 120 patients (10.8%, 13/120) experienced clinical aggravation to need new oxygen requirement.UV = unvaccinated, FV = fully vaccinated.


1. Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020; 383(27):2603–2615. PMID: 33301246.
2. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021; 384(5):403–416. PMID: 33378609.
3. Falsey AR, Sobieszczyk ME, Hirsch I, Sproule S, Robb ML, Corey L, et al. Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine. N Engl J Med. 2021; 385(25):2348–2360. PMID: 34587382.
4. Yi S, Kim JM, Choe YJ, Hong S, Choi S, Ahn SB, et al. SARS-CoV-2 delta variant breakthrough infection and onward secondary transmission in household. J Korean Med Sci. 2022; 37(1):e12. PMID: 34981682.
5. Wi YM, Kim SH, Peck KR. An outbreak of breakthrough infections by the SARS-CoV-2 delta variant in a psychiatric closed ward. J Korean Med Sci. 2022; 37(4):e28. PMID: 35075827.
6. Tang P, Hasan MR, Chemaitelly H, Yassine HM, Benslimane FM, Al Khatib HA, et al. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 delta variant in Qatar. Nat Med. 2021; 27(12):2136–2143. PMID: 34728831.
7. Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 (delta) variant. N Engl J Med. 2021; 385(7):585–594. PMID: 34289274.
8. Lin DY, Gu Y, Wheeler B, Young H, Holloway S, Sunny SK, et al. Effectiveness of COVID-19 vaccines over a 9-month period in North Carolina. N Engl J Med. 2022; 386(10):933–941. PMID: 35020982.
9. Lambden S, Laterre PF, Levy MM, Francois B. The SOFA score-development, utility and challenges of accurate assessment in clinical trials. Crit Care. 2019; 23(1):374. PMID: 31775846.
10. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373–383. PMID: 3558716.
11. 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.
12. Korea Disease Control and Prevention Agency. Global trends and characteristics of the SARS-CoV-2 delta variant. Public Health Wkly Rep. 2021; 14(33):2363–2365.
13. Korea Disease Control and Prevention Agency. July 2021 status and characteristics of the COVID-19 variant virus outbreak in the Republic of Korea. Public Health Wkly Rep. 2021; 14(48):3388–3396.
14. Sun J, Zheng Q, Madhira V, Olex AL, Anzalone AJ, Vinson A, et al. Association between immune dysfunction and COVID-19 breakthrough infection after SARS-CoV-2 vaccination in the US. JAMA Intern Med. 2022; 182(2):153–162. PMID: 34962505.
15. Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, et al. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021; 326(20):2043–2054. PMID: 34734975.
16. Sieswerda E, de Boer MG, Bonten MM, Boersma WG, Jonkers RE, Aleva RM, et al. Recommendations for antibacterial therapy in adults with COVID-19 - an evidence based guideline. Clin Microbiol Infect. 2021; 27(1):61–66. PMID: 33010444.
17. Shin DH, Kang M, Song KH, Jung J, Kim ES, Kim HB. A call for antimicrobial stewardship in patients with COVID-19: a nationwide cohort study in Korea. Clin Microbiol Infect. 2021; 27(4):653–655. PMID: 33137513.
18. Ong SW, Hui TC, Lee YS, Haja Mohideen SM, Young BE, Tan CH, et al. High-risk chest radiographic features associated with COVID-19 disease severity. PLoS One. 2021; 16(1):e0245518. PMID: 33444415.
19. Jung J, Lee J, Park H, Lim YJ, Kim EO, Park MS, et al. Nosocomial outbreak by delta variant from a fully vaccinated patient. J Korean Med Sci. 2022; 37(17):e133. PMID: 35502502.
Full Text Links
  • JKMS
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr