Previous SARS-CoV-2 Infection, Age, and Frailty Are Associated With 6-Month Vaccine-Induced Anti-Spike Antibody Titer in Nursing Home Residents

Abstract

Objectives: Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group.

Design: Longitudinal cohort study.

Setting and participants: Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine.

Methods: Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity.

Results: Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32-3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89-4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: -0.05; 95% CI: -0.08 to -0.02; P < .001) and frailty (β: -0.22; 95% CI: -0.33 to -0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity.

Conclusions and implications: In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population.

Keywords: COVID-19; Nursing homes; SARS-CoV-2.0; antibody; long-term care; vaccine.

Fig. 1

Antibody response to SARS-CoV-2 mRNA vaccine in older nursing home residents. (A) Antibody responses in all participants (N = 86) at baseline, 5 weeks, and 6 months after vaccination (top). (B) Antibody responses in SARS-CoV-2–naïve individuals (bottom left). (C) Antibody responses in participants with previous SARS-CoV-2 infection (bottom right).

Fig. 2

Neutralization capacity of the antibody response to SARS-CoV-2 vaccination. (A) Correlation between neutralization capacity and anti-Spike antibody titer (n = 24) (top left). (B) Neutralization capacity at baseline, 5 weeks, and 6 months post vaccination with a SARS-CoV-2 mRNA vaccine (top right). (C) Neutralization capacity over time in SARS-CoV-2–naïve participants. (D) Neutralization capacity over time in participants previously infected with SARS-CoV-2. Note: Neutralization values are presented as a percentage of a pool of 6 pre-pandemic controls, with greater. Note: Neutralization values are presented as a percentage of a pool of 6 pre-pandemic controls, with greater values indicating poorer neutralization capacity.