The Effect of the Immunization Schedule and Antibody Levels (Anti-S) on the Risk of SARS-CoV-2 Infection in a Large Cohort of Healthcare Workers in Northern Italy

Abstract

Given their occupational risk profile, HCWs were the first to receive anti-SARS-CoV-2 vaccination. However, breakthrough infections remained common, mainly sustained by new SARS-CoV-2 variants of concern (VOCs) that rapidly spread one after another in Italy. Evidence suggests that the measured level of anti-SARS-CoV-2 antibodies does not clearly predict the level of protection conferred by either natural infection or vaccine-induced immunization, highlighting the need for further study on the diversity in susceptibility to SARS-CoV-2 infection. The present study aimed to characterize different risk profiles for SARS-CoV-2 infection in HCWs who had recently received the booster dose, and who were classified according to their immunization profile. The very small number of workers infected during the 8 months following the primary-cycle administration represents proof of the vaccine's effectiveness against non-omicron strains. The comparison among different immunization profiles showed that hybrid immunization (vaccine plus natural infection) elicits higher antibody levels. However, hybrid immunization does not always provide better protection against reinfection, thus suggesting that the immunization profile plays a major role as a virus-host interaction modifier. Despite the high resistance to the reinfection, the peri-booster infection had a not-neglectable infection rate (5.6%), this further reinforcing the importance of preventive measures.

Keywords: COVID-19 vaccines; HCWs; SARS-CoV-2; hybrid immunization; immunization profiles; serological response.

Figure 1

Trends of the anti-SARS-CoV-2-S levels (U/mL) over time in the whole sample stratified by the timing of the occurrence of previous SARS-CoV-2 infection. Curves were obtained from the predictions of the bootstrapped piecewise linear mixed model adjusted by age and gender. The day of the booster injection was set as the reference for time. The gap between the two periods (before and after the booster) was due to the absence of an anti-S serological assay performed during the interval between T₃ and T₄, when the booster dose was administered. Due to the infections occurred in such interval the no previous infection group was split in two, originating the peri-booster infection group, which curve can be only seen on the right part of the figure.

Figure 2

Kaplan–Meier curves measuring time without infection obtained according to the considered immunization profiles. The booster injection date was considered a reference for the time axis.