Ann Lab Med.  2024 Jan;44(1):64-73. 10.3343/alm.2024.44.1.64.

Association Between Low Anti-spike Antibody Levels After the Third Dose of SARS-CoV-2 Vaccination and Hospitalization due to Symptomatic Breakthrough Infection in Kidney Transplant Recipients

• Han A
• Min S
• Jo EA
• Lee H
• Kim YC
• Han SS
• Kang HG
• Ahn YH
• Oh I
• Song EY
• Ha J

• KMID: 2550224
• DOI: http://doi.org/10.3343/alm.2024.44.1.64

Abstract

Background
Whether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients.
Methods
In total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022. The Abbott SARS-CoV-2 IgG II Quant test (Abbott, Chicago, IL, USA) was performed within three weeks before and four weeks after the third vaccination. The incidence of symptomatic breakthrough infection and hospitalization from two weeks to four months post-third vaccination was recorded.
Results
After the third vaccination, the seropositive rate and median antibody titer of the 287 patients increased from 57.1% to 82.2% and from 71.7 (interquartile range [IQR] 7.2– 402.8) to 1,612.1 (IQR 153.9–5,489.1) AU/mL, respectively. Sixty-four (22.3%) patients had symptomatic breakthrough infections, of whom 12 required hospitalization. Lower anti-receptor-binding domain (RBD) IgG levels ( < 400 AU/mL) post-third vaccination were a risk factor for symptomatic breakthrough infection (hazard ratio [HR] = 3.46, P < 0.001). Anti-RBD IgG levels < 200 AU/mL were a critical risk factor for hospitalization (HR = 36.4, P = 0.007).
Conclusions
Low anti-spike IgG levels after third vaccination in kidney transplant recipients were associated with symptomatic breakthrough infection and, particularly, with hospitalization during the Omicron surge. These data can be used to identify patients requiring additional protective measures, such as passive immunization using monoclonal antibodies.

Keyword

Anti-SARS-CoV2 antibody; Breakthrough infection; COVID-19; Kidney transplant; Vaccine

Figure

• 

  Fig. 1 Anti-RBD IgG levels according to the primary vaccine type before and after four weeks and three months following the third vaccination. Abbreviation: RBD, receptor-binding domain.

• 

  Fig. 2 Post-third vaccination anti-spike IgG antibody levels according to the rate of symptomatic breakthrough infections or hospitalization. The P-values for all pairwise comparisons by pairwise Wilcoxon tests are as follows: no infection vs. infection without hospitalization, P=0.040; infection without hospitalization vs. infection with hospitalization, P=0.016; no infection vs. infection with hospitalization, P=0.0001. *P<0.05, **P<0.005, ***P<0.001. Abbreviation: RBD, receptor-binding domain.

• 

  Fig. 3 Kaplan–Meier survival curves of risk of symptomatic breakthrough infection or hospitalization according to post-third vaccination anti-spike IgG levels. (A) When the patients were regrouped according to an anti-spike IgG level of 400 AU/mL (determined based on a ROC curve; data not shown), the risk of developing symptomatic breakthrough infection differed significantly between the groups (log-rank test, P< 0.0001). (B) When the patients were regrouped according to an anti-RBD IgG level of 200 AU/mL (determined based on a ROC curve; data not shown), the risk of hospitalization was higher in patients with anti-RBD IgG <200 AU/mL than in patients with anti-RBD IgG ≥200 AU/mL (log-rank test, P<0.0001). Abbreviation: RBD, receptor-binding domain.

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