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. 2023 Jul 6;11(7):1214.
doi: 10.3390/vaccines11071214.

Cellular and Humoral Immune Responses after Breakthrough Infection in Patients Undergoing Hemodialysis

Masataro Toda  1 , Ayumi Yoshifuji  1   2 , Tetsuo Nakayama  3 , Setsuko Mise-Omata  4 , Emi Oyama  1 , Yoshifumi Uwamino  2   5 , Ho Namkoong  2 , Motoaki Komatsu  1 , Akihiko Yoshimura  4 , Naoki Hasegawa  2 , Kan Kikuchi  6 , Munekazu Ryuzaki  1
Affiliations

Cellular and Humoral Immune Responses after Breakthrough Infection in Patients Undergoing Hemodialysis

Masataro Toda et al. Vaccines (Basel). .

Abstract

Coronavirus disease 2019 (COVID-19) following primary immunization (breakthrough infection) has been reported in hemodialysis patients; however, their post-infection immune status remains unclear. We evaluated the humoral and cellular immunity of hemodialysis patients after breakthrough infection. Hemodialysis patients who had received primary immunization against COVID-19 at least six months prior to the study but developed mild/moderate COVID-19 before a booster dose (breakthrough infection group) and hemodialysis patients who were not infected with COVID-19 but received a booster dose (booster immunization group) were recruited. In both groups, SARS-CoV-2 antigen-specific cytokines and IgG levels were measured three weeks after infection or three weeks after receiving a booster dose. Memory T and B cells were also counted in the breakthrough infection group using flow cytometry three weeks after infection. Significantly higher SARS-CoV-2 antigen-specific IgG, IFN-γ, IL-5, TNF-α, and IL-6 levels occurred in the breakthrough infection group compared to the booster immunization group (p = 0.013, 0.039, 0.024, 0.017, and 0.039, respectively). The SARS-CoV-2 antigen-specific IgG and cytokine levels were not significantly different between the two groups. The breakthrough infection group had significantly higher percentages of central and effector memory T cells and regulatory T cells than the comparison group (p = 0.008, 0.031, and 0.026, respectively). Breakthrough infections may induce stronger cellular and humoral immune responses than booster immunizations in hemodialysis patients.

Keywords: COVID-19; booster vaccination; breakthrough infection; hemodialysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Anti-S1 antibody titers. Anti-S1 antibody titers were measured two weeks after infection in the breakthrough infection group and three weeks after receiving the booster dose in the booster immunization group. HD patients in the breakthrough infection group had a significantly higher anti-S1 antibody titer than those in the booster immunization group (p = 0.004). In addition, in the breakthrough infection group, HD patients tended to have higher anti-S1 antibody titers than the controls; however, in the booster immunization group, the anti-S1 antibody titers were similar between the HD patients and the controls. **: p ≤ 0.01, *: p < 0.05. HD: hemodialysis.
Figure 2
Figure 2
Cytokine levels in response to SARS-CoV-2 antigens. The cytokine levels were measured using SARS-CoV-2 antigen-stimulated blood samples collected two weeks after infection in the breakthrough infection group and three weeks after receiving the booster dose in the booster immunization group. IFN-γ, IL-5, TNF-α, and IL-6 were significantly higher in HD patients after breakthrough infection compared to HD patients who received a booster immunization (p = 0.039, 0.037, 0.039, and 0.017, respectively). There was no significant difference in all the cytokine levels between the HD patients and control patients in both the breakthrough infection and booster immunization groups. *: p < 0.05. HD: hemodialysis; G-CSF: granulocyte-colony stimulating factor; GM-CSF: granulocyte–macrophage colony-stimulating factor; IFN: interferon; IL: interleukin; TNF-α: tissue necrotic factor-α.
Figure 3
Figure 3
The analysis of memory T and B cells. Peripheral blood mononuclear cells were sampled two weeks after breakthrough infection and were stained with monoclonal antibodies, and memory T cells and anti-RBD IgG antibody-expressing B cells were counted using flow cytometry. (a) The number of anti-RBD IgG antibody-expressing B cells tended to be higher in HD patients than in control patients. (b) The percentage of central memory T cells was significantly higher in HD patients than in control patients (p = 0.008). The percentage of effector memory T cells was significantly higher in HD patients than in control patients (p = 0.031). (c) The percentage of regulatory T cells was significantly higher in HD patients than in control patients (p = 0.026). The representative fluorescence-activated cell sorting (FACS) profiles for control and HD patients are shown above each figure (a–c). **: p ≤ 0.01; *: p < 0.05. HD: hemodialysis.
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