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. 2023 Dec 1;11(12):1803.
doi: 10.3390/vaccines11121803.

Humoral Response Kinetics and Cross-Immunity in Hospitalized Patients with SARS-CoV-2 WT, Delta, or Omicron Infections: A Comparison between Vaccinated and Unvaccinated Cohorts

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Humoral Response Kinetics and Cross-Immunity in Hospitalized Patients with SARS-CoV-2 WT, Delta, or Omicron Infections: A Comparison between Vaccinated and Unvaccinated Cohorts

Hyunhye Kang et al. Vaccines (Basel). .

Abstract

With the ongoing evolution of severe acute respiratory virus-2 (SARS-CoV-2), the number of confirmed COVID-19 cases continues to rise. This study aims to investigate the impact of vaccination status, SARS-CoV-2 variants, and disease severity on the humoral immune response, including cross-neutralizing activity, in hospitalized COVID-19 patients. This retrospective cohort study involved 122 symptomatic COVID-19 patients hospitalized in a single center. Patients were categorized based on the causative specific SARS-CoV-2 variants (33 wild-type (WT), 54 Delta and 35 Omicron) and their vaccination history. Sequential samples were collected to assess binding antibody responses (anti-S/RBD and anti-N) and surrogate virus neutralization tests (sVNTs) against WT, Omicron BA.1, and BA.4/5. The vaccinated breakthrough infection group (V) exhibited higher levels of anti-S/RBD compared to the variant-matched unvaccinated groups (UVs). The Delta infection resulted in a more rapid production of anti-S/RBD levels compared to infections with WT or Omicron variants. Unvaccinated severe WT or Delta infections had higher anti-S/RBD levels compared to mild cases, but this was not the case with Omicron infection. In vaccinated patients, there was no difference in antibody levels between mild and severe infections. Both Delta (V) and Omicron (V) groups showed strong cross-neutralizing activity against WT and Omicron (BA.1 and BA.4/5), ranging from 79.3% to 97.0%. WT (UV) and Delta (UV) infections had reduced neutralizing activity against BA.1 (0.8% to 12.0%) and BA.4/5 (32.8% to 41.0%). Interestingly, patients who received vaccines based on the ancestral spike exhibited positive neutralizing activity against BA.4/5, even though none of the study participants had been exposed to BA.4/5 and it is antigenically more advanced. Our findings suggest that a previous vaccination enhanced the humoral immune response and broadened cross-neutralizing activity to SARS-CoV-2 variants in hospitalized COVID-19 patients.

Keywords: SARS-CoV-2; humoral immunity; neutralization; vaccine; variant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study enrollment and Determination of SARS-CoV-2 variants. n, total number of patients in each group; UV, unvaccinated; V, vaccinated.
Figure 2
Figure 2
Kinetics of anti-S/RBD and anti-N responses. Kinetics of binding antibody response to WT, Delta and Omicron variants from unvaccinated (A,C) and vaccinated (B,D) patients. The median antibody titers of WT, Delta, and Omicron infected individuals are indicated by the squares, triangles, and circles, respectively, and the error bars indicate 95% CI. ns, not significant, * p < 0.05, ** p < 0.01, *** p < 0.001 by Mann-Whitney U test.
Figure 3
Figure 3
Anti-S/RBD and anti-N antibody levels stratified by disease severity in hospitalized patients infected with SARS-CoV-2 WT, Delta or Omicron variants. Comparison of anti-S/RBD (A,B) and anti-N (C,D) antibody levels in patients with vaccinated breakthrough and unvaccinated infections between mild and severe patients with exposure to WT, Delta and Omicron variants, separately. The WT infected group includes only unvaccinated patients. Each group is color-coded as follows: WT (UV), purple; Delta (UV), light blue; Omicron (UV), orange; Delta (V), blue; Omicron (V), red. The median antibody titers are indicated by the horizontal lines and the error bars indicate 95% CI. ns, not significant, * p < 0.05, ** p < 0.01, *** p < 0.001 by Mann-Whitney U test.
Figure 4
Figure 4
Neutralizing activity to Wild type and Omicron variants (BA.1 and BA/4/5) in hospitalized patients infected with SARS-CoV-2 WT, Delta or Omicron variants. Neutralizing activity against Wild type (WT) (A), Omicron BA.1 (B) and Omicron BA.4/5 (C) in each vaccine and variant combination. Each group is color-coded as follows: WT (UV), purple; Delta (UV), light blue; Omicron (UV), orange; Delta (V), blue; Omicron (V), red. The horizontal dotted line represents the cutoff of the assay (30%). Median percent inhibition of neutralizing antibodies is indicated by the horizontal lines and the error bars indicate 95% CI. ns, not significant, * p < 0.05, by Mann-Whitney test.
Figure 5
Figure 5
Comparison of neutralizing activity to Wild type and Omicron variants (BA.1 and BA.4/5) in unvaccinated (A) and vaccinated (B) patients with SARS-CoV-2 WT, Delta or Omicron variants. The horizontal dotted lines represent the cutoff of the assay (30%). Each group is color-coded as follows: WT (UV), purple; Delta (UV), light blue; Omicron (UV), orange; Delta (V), blue; Omicron (V), red. Dotted line connecting points indicated immunocompromised patients. Empty circle indicates patients with mild disease and full circle indicates patients with severe disease.

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References

    1. Barouch D.H. COVID-19 Vaccines—Immunity, Variants, Boosters. N. Engl. J. Med. 2022;387:1011–1020. doi: 10.1056/NEJMra2206573. - DOI - PMC - PubMed
    1. Lee J., Lee D.G., Jung J., Ryu J.H., Shin S., Cho S.Y., Lee R., Oh E.J. Comprehensive assessment of SARS-CoV-2 antibodies against various antigenic epitopes after naive COVID-19 infection and vaccination (BNT162b2 or ChAdOx1 nCoV-19) Front. Immunol. 2022;13:1038712. doi: 10.3389/fimmu.2022.1038712. - DOI - PMC - PubMed
    1. Jeong S., Kim J.S., Lee S.K., Cho E.J., Hyun J., Song W., Kim H.S. Tracking the Genomic Evolution of SARS-CoV-2 for 29 Months in South Korea. Viruses. 2023;15:873. doi: 10.3390/v15040873. - DOI - PMC - PubMed
    1. Scovino A.M., Dahab E.C., Vieira G.F., Freire-de-Lima L., Freire-de-Lima C.G., Morrot A. SARS-CoV-2’s Variants of Concern: A Brief Characterization. Front. Immunol. 2022;13:834098. doi: 10.3389/fimmu.2022.834098. - DOI - PMC - PubMed
    1. Blaszczuk A., Michalski A., Malm M., Drop B., Polz-Dacewicz M. Antibodies to NCP, RBD and S2 SARS-CoV-2 in Vaccinated and Unvaccinated Healthcare Workers. Vaccines. 2022;10:1169. doi: 10.3390/vaccines10081169. - DOI - PMC - PubMed

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