Immune Responses to SARS-CoV-2 Infection and Vaccine in a Big Italian COVID-19 Hospital: An 18-Month Follow-Up

Abstract

Objectives: This is a longitudinal prospective study which was designed to assess the trend of anti-SARS-CoV-2 antibodies targeting the Spike (anti-S) and Nucleocapside protein (anti-N) viral antigens over a 9-month period after the administration of an anti-SARS-CoV-2 vaccine in a big COVID-19 hospital located in Northern Italy. Participants: 7411 vaccinated workers were included in a linear mixed-effect model analysis performed to model the anti-S decay over the 9 months following the vaccination, during serological screening performed approximately 2, 4, and 9 months following the first jab administration. Serological tests performed in the 9 months preceding vaccine administration were retrospectively analysed to identify the burden of infections occurring before vaccination. Results: The serological assays were used for monitoring the antibody titres during the observational period. Vaccination significantly reduced the rate of infection and elicited a specific humoral response, which lasted during the whole observational period (9 months). A decay was observed in all considered subgroups. At 35 weeks, workers with no history of pre-vaccine infection showed a significantly lower anti-S titre (−2522 U/mL on average (−2589.7 to −2445.7)); younger workers showed significantly higher anti-S titres (140.2 U/mL on average (82.4 to 201.3)). Only seven immunocompromised workers did not show significant levels of anti-S antibodies; three of them, all females, showed a specific T-cell response. Conclusions: Comparing the 9-month periods before and after the first vaccine dose, a significant reduction in infection rate was observed (1708 cases vs. 156). Pre-vaccine infection, especially if contracted during the first pandemic wave, greatly enhanced the response to vaccination, which was significantly affected also by age both in extent and duration (inversely related). A gender effect on the T-cell immune response was observed in a small group of workers who did not produce antibodies after vaccine administration.

Genome‐wide association studies of response and side effects to the BNT162b2 vaccine in Italian healthcare workers: Increased antibody levels and side effects in carriers of the HLA‐A*03:01 allele

“…The samples analyzed in this study were a subset ( N = 926) of a previously described cohort 23 . Briefly, the original cohort included HCWs employed in ASST Spedali Civili di Brescia (Brescia, Italy) assembled to study the proportion, level and the determinants of humoral response from 21 days to up to 1 year after the first dose of anti SARS‐CoV‐2 vaccine.…”

“…The samples analyzed in this study were a subset (N = 926) of a previously described cohort. 23 Briefly, the original cohort included HCWs employed in ASST Spedali Civili di Brescia (Brescia, Italy) assembled to study the proportion, level and the determinants of humoral response from 21 days to up to 1 year after the first dose of anti SARS-CoV-2 vaccine. The vast majority of participants received a 2nd dose of BNT162b2 vaccine 21 days after the 1st dose; results collected at 2 (T1) and 4 months (T2) after the 1st dose administration have been included in the present study.…”

“…As previously reported, 23 vaccine response (from T1 onwards) was assessed using the Electrochemiluminescence immunoassay (ECLIA) Elecsys ® anti SARS CoV2 S for anti-S (IgG/A/M) detection (Roche Diagnostics International Ltd, Rotkreuz, Switzerland). Elecsys ® Anti-SARS-CoV-2-S is an immunoassay for the in vitro quantitative determination of antibodies (IgG/A/M) targeting the SARS-CoV-2 Spike (S) protein receptor binding domain (RBD) in human serum and plasma.…”

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

“…Based on a meta-analysis of 97 publications from 2020, the overall prevalence of SARS-CoV-2 infection in HCWs was 11% according to PCR test results and 7% according to serological test results [3]. However, in Northern Italy, higher infection rates have been reported [4,5].…”

“…Given their occupational risk profile, HCWs were the first to receive anti-SARS-CoV-2 vaccination starting on 27 December 2020. In May 2021, when vaccination against SARS-CoV-2 became mandatory for Italian HCWs, the vast majority of them were vaccinated [5]. However, breakthrough infections remained common [9], mainly sustained by the spread of new SARS-CoV-2 variants of concern (VOCs) that rapidly spread one after another in our country: alpha (B.1.1.7 and B.1.1.7+E484K), gamma (P.1), delta (B.1.617.2), and omicrons (B.1.1.529) [10].…”