Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections

SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron

Characteristics Associated with Serological Covid-19 Vaccine Response and Durability in an Older Population with Significant Comorbidity:The Danish Nationwide ENFORCE Study

OBJECTIVES: To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and durability of vaccine-induced antibodies. METHODS: Adults without history of SARS-CoV-2 infection from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase IV study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90 and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 post-1(st) vaccination. Non-durable vaccine-response was defined as day 90 responders that no longer had significant responses by day 180. RESULTS: Of 6544 participants completing two vaccine doses (median age 64, interquartile range:54–75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by a mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hypo-responsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG; 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type and number of co-morbidities were associated with all four outcomes. Additionally, age >=75y was associated with hypo-responsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds-ratio:1.59, 95% confidence interval:1.25–2.01) but not for Spike IgG. CONCLUSIONS: Comorbidity, male sex and vaccine type were risk factors for hypo-responsiveness and non-durable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-2(nd) vaccination levels for most individuals after 6 months

Impact of age and comorbidities on SARS-CoV-2 vaccine-induced T cell immunity

Abstract Background Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. Methods In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51–72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. Results We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. Conclusions SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization