Abstract
We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4 + and CD8 + T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4 + and CD8 + T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC 50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4 + (p = 0.82) and CD8 + (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4 + or CD8 + T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.
Keywords: Comirnaty® COVID-19 vaccine; SARS-CoV-2 Omicron variant; anti-spike antibodies; breakthrough infection; neutralizing antibodies; nursing home residents; spike-reactive T cells.
【저자키워드】 Neutralizing antibodies, Breakthrough infection, anti-spike antibodies, Comirnaty® COVID-19 vaccine, SARS-CoV-2 Omicron variant, nursing home residents, spike-reactive T cells., 【초록키워드】 COVID-19, neutralizing antibody, SARS-CoV-2, Vaccine, COVID-19 vaccine, Neutralizing antibodies, spike, antibody, T cells, nursing home, variant, Infection, risk, cytokine, omicron, CD4, CD8, observational study, flow cytometry, Receptor binding domain, Peripheral blood, T cell, Pseudotyped virus, Neutralization assay, symptomatic, female, Omicron variant, Neutralizing, Breakthrough infection, chemiluminescent immunoassay, total antibody, homologous, booster dose, predict, anti-spike antibodies, Anti-spike, SARS-CoV-2 spike, Immunological response, Frequency, anti-RBD, blood levels, both groups, median age, participant, individual level, SARS-CoV-2-S, likelihood, intracellular cytokine staining, reactive, subsequent, investigated, detectable, evaluated, median, comparable, were measured, quantified, immune parameter, in both groups, not correlated, uninfected participant, 【제목키워드】 COVID-19, SARS-CoV-2, variant, homologous, dose,