Front Immunol. 2023;14:1106664.

Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

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제1저자 이찬미, 최평균, 강창경 · 교신저자 박완범, 박상원, 신현무

PMID 37033936 PMC10073433 DOI 10.3389/fimmu.2023.1106664 IF 7 감염내과

소속 (9)

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Department of Anatomy & Cell Biology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
BK21 FOUR Biomedical Science Project, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Wide River Institute of Immunology, Seoul National University, Hongcheon, Republic of Korea.

Abstract

BACKGROUND Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19.

METHODS We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively.

RESULTS Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19.

CONCLUSIONS Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Keywords

COVID-19SARS-CoV-2antibodybreakthrough infectionimmune response

Figures

**Figure 1** Humoral immune responses to SARS-CoV-2 within 1 week after symptom onset in patients with breakthrough COVID-19. **(A)**. Anti-S1 IgG antibody titers in the control (vaccinated subjects without infection), severe, and non-severe groups. **(B)**. Anti-S1 IgG antibody titers according to the number of days from symptom onset. **(C)**. IgG-binding activities to RBD_WT. **(D)**. IgG-binding activities to RBD_Delta. The dotted line shows the positive cutoff value of the anti-S1 IgG O.D. ratio. Vertical and horizontal lines indicate the median with the interquartile range.

**Figure 2** Anti-S1 IgG antibody kinetics over time after SARS-CoV-2 infection in vaccinated and unvaccinated patients. Serial antibody titers in vaccinated patients with non-severe (n = 10) and severe (n = 17) breakthrough COVID-19 and unvaccinated patients with SARS-CoV-2 infection (n = 7) are plotted. The dotted line shows the positive cutoff value of the anti-S1 IgG O.D. ratio.

**Figure 3** T cell responses within 1 week after diagnosis of breakthrough COVID-19. **(A)** AIM⁺ CD4⁺ T cells stimulated with the whole spike Ag, and the matched WT and Delta Ags. **(B)** AIM⁺ CD8⁺ T cells stimulated with the whole spike Ag, and the matched WT and Delta Ags. The control group denotes vaccinated subjects without breakthrough COVID-19. Vertical and horizontal lines indicate the median with the interquartile range.

그림 출처: PubMed Central 공개 논문 (PMC10073433)

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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