Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNedshort- And long-term Immune reSponSe evAluatioN in health Care workErs

Objective To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. Methods This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription–polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. Results Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. Conclusion The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals. Abbreviations and Acronyms: BAU, binding antibody unit; IMPDH, inosine-5′-monophosphate dehydrogenase; IQR, interquartile range; MPA, mycophenolic acid; RT-PCR, reverse transcription–polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VOC, variant of concern On December 21, 2020, the European Commission granted the first European conditional marketing authorization for the active immunization of adults older than 16 years with the BNT162b2 vaccine (Pfizer-BioNTech). This approval was the result of an unprecedented effort undertaken by companies, regulatory authorities, and academia that enabled the development of vaccines in as short as 10 months. Soon after the approval, vaccination campaigns for health care workers across the United States and Europe began immediately. As of May 10, 2021, the Centers for Disease Control and Prevention COVID-19 vaccination tracker has counted a total of 259,716,989 doses administered in the United States (https://covid.cdc.gov/covid-data-tracker/#vaccinations). BNT162b2 is a vaccine containing a nucleoside-modified messenger RNA (mRNA) able to encode the full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein, enclosed within a lipid nanoparticle shell with the role of protecting it from degradation and thus promoting delivery to the target cell. In the phase 3 trial that led to market approval, the BNT162b2 vaccine demonstrated 95% clinical efficacy in preventing COVID-19 (95% CI, 90.3 to 97.6; >0.9999 posterior probability of true vaccine efficacy >30%).1 The immunogenicity of BNT162b2 had previously been evaluated in smaller phase 1-2 trials. These demonstrated that for all doses tested, anti-S IgG antibody production was detectable at 21 days after the first dose, with a boost effect from the second dose, leading to a peak antibody response within the next 7 days. A 50% neutralization titer was found to peak at 7 days after the second dose in the population between 18 and 55 years of age; but in the population between 65 and 85 years of age, the peak of production was reached 14 days after the second dose.2 The rapid approval of COVID-19 vaccines, dictated by the impending need, previously had led to a poor representation, in clinical trials, of variability in background and clinical and demographic conditions of the population to which clinical practice studies are called to respond. BNT162b2 clinical trials systematically excluded immunosuppressed individuals and those with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention. In addition, the immunogenicity of the BNT162b2 at the approved dose of 30 μg has been evaluated in only 12 participants in the age group of 18 to 55 years and 12 in the age group of 65 to 85 years.2 Data on large populations, more representative of the general population in individual epidemiologic settings, are therefore urgently needed. The RENAISSANCE study is an observational study that aimed to evaluate the serologic response to the BNT162b2 COVID-19 vaccine in the staff of the main COVID-19 reference hospital of Milan, Italy, at multiple time points after a hospital-wide vaccination campaign. Here we report the efficacy of the BNT162b2 vaccine in promoting anti-S antibody production and conferring protection against symptomatic and severe forms of COVID-19 at day 14 after the second vaccine dose in more than 2500 health care workers.