Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection

Abstract

The immune response after SARS-CoV-2 vaccine administration appears to be characterized by high inter-individual variation, even in SARS-CoV-2 positive subjects, who could have experienced different post-infection, unresolved conditions. We monitored anti-SARS-CoV-2 IgG levels and kinetics along with circulating biomarkers in a cohort of 175 healthcare workers during early immunization with COVID-19 mRNA-LNP BNT162b2 vaccine, to identify the associated factors. Subjects with a previous SARS-CoV-2 infection were characterized by higher BMI and CRP levels and lower neutrophil count with respect to naïve subjects. Baseline IgG levels resulted associated with CRP independently on BMI and inflammatory diseases. Among 137 subjects undergoing vaccination and monitored after the first and the second dose, three kinetic patterns were identified. The pattern showing a rapid growth was characterized by higher IgG levels at baseline and higher CRP and MCHC levels than negative subjects. Subjects previously exposed to SARS-CoV-2 showed higher levels of CRP, suggesting persistence of unresolved inflammation. These levels are the main determinant of IgG levels at baseline and characterized subjects belonging to the best performing, post-vaccine antibody kinetic pattern.

Figure 1

Baseline IgG levels and time distance (days) between measurement and SARS-CoV-2 first negative nasal swab among subjects previously positive to RT-PCR, stratified by (panel A) history of symptoms and (panel B) positivity duration (N = 48).

Figure 2

Antibody levels following vaccination (baseline—T0, 20 days after first dose—T1, 14 days after 2nd dose—T2): pattern shape, coefficients and goodness-of-fit parameters for the sub-population groups identified from trajectory analyses (best model), in the overall sample with repeated serum IgG measurements at T0, T1 and T2 (n = 137). Y log scale. ^: On the log-transformed serum IgG variable; nr not relevant (linear model); *: Bayesian Information Criterion, on the number of observations (n = 137 unique subjects, 3 time measurement each); **: Bayesian Information Criterion, on the number of unique subjects (n = 137 unique subjects).