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

Abstract

Objective To evaluate the SARS-CoV-2 anti-spike IgG antibodies production after the vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in healthcare workers. Patients and methods This prospective observational study (RENAISSANCE) had as primary endpoint the evaluation of serologic response to BNT162b2 14-days after second dose. SARS-CoV-2 anti-spike IgG antibodies were evaluated with LIAISON® SARS-CoV-2 TrimericS IgG assay, able to detect presence of both binding and neutralizing antibodies for trimeric Spike glycoprotein. Subjects were recruited from February 1, 2021 to February 22, 2021. Occurrence of vaccine-breakthrough infections was assessed by RT-PCR on symptomatic/contact cases, up to June 6, 2021. Results Out of 2569 staff only were 4 non-responders (0.16%, 95%CI:0.04%-0.41%). All 4 non-responders were severely immunosuppressed and on treatment with mycophenolate mofetil/mycophenolic acid. At 14-days since 2° dose, the 67.5% of staff had anti-S IgG titers ≥2000 BAU/mL, 19.2% between 1500- 2000 BAU/ml, 9.8% between 1000-1500 BAU/ml, and 3.4% ≤1000 BAU/ml. Females had a higher probability of having higher titers than males (64.5% [1044/1618] vs. 58.3% [410/703]; p=0.005). This was confirmed after adjusting for age group (OR [95%CI]: 1.275 [1.062-1.531]; p=0.009). Four months after the end of vaccination program, only 13 subjects (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 non-responder. This subject was the only requiring hospitalization for severe COVID-19. Conclusion Vaccination campaign among healthcare workers at the ASST GOM Niguarda has resulted in a significative serologic response, and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised subjects.

Impaired seroconversion after SARS-CoV-2 mRNA vaccines in patients with solid tumours receiving anticancer treatment

“…About 6% of cancer patients in treatment failed to develop an immune response after mRNA vaccination, as compared to only 0.2% in controls, accounting for a 30-fold higher probability. Of note, all 4 subjects with no antibodies in the control group were on immunosuppressive treatment with mycophenolate mofetil at the time of vaccination, impacting on seroconversion 28 .…”

“…Seroconversion was evaluated as the production of anti-S immunoglobulin G (IgG) after the completion of a vaccination course (2 doses of BNT162b2 or mRNA-1273) and compared with a cohort of historical controls from a surveillance program led from December 2020 to February 2021 in healthcare workers at the same institution (RENAISSANCE trial) 28 . The neutralizing activity of anti-S IgG antibodies was measured in the cohort of cancer patients to support the accuracy of immunogenicity.…”

“…Assuming a 99.9% seroconversion rate (H 0 ) according to the preliminary analysis in healthy controls (RENAISSANCE trial 28 ), and with at least 168 vaccinated fragile patients, we have 90% power to observe an absolute reduction of 4% in seroconversion rate (H 1 ), with a clinical significant δ threshold of at least 1% reduction, and a type I error of 2.5%. Clinically relevant variables were correlated with seroconversion rate and reported with proper significance tests and in a univariate/multivariate logistic regression model.…”

“…To this aim, we designed SINFONIA-V, a mono-institutional prospective observational study carried out at a comprehensive cancer center (Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy), comparing results with those of an extensive surveillance program performed in the same institution in healthcare workers 28 .…”

Estimation of R0 for the spread of SARS-CoV-2 in Germany from Excess Mortality

“…20% who have already been infected, an estimated 20% immunity due to the vaccinations can be added (vaccination rate multiplied by effectiveness), so that we assume that the proportion of immunity towards SARS-CoV-2-infection in Germany is less than expected due to waning immunity. In spite of this, the protection by vaccination against severe infection and death by SARS-CoV-2 infection is well established to be high 30 . However, this is not the focus here but rather transmission of the virus taking also recent and longer time ago previously vaccinated people also into account, and thus the influence of all these different factors on the resulting R0.…”