== Host factors influence around the dynamics of anti-S/RBD IgG antibodies in healthcare workers, Romania, 2021. variant. Nevertheless, breakthrough infections were present in 6.65% of all participants, without any correlation with the previous level of anti-S/RBD IgG. Protection against the ancestral and Omicron variants is maintained at least three months after a booster in HCW, possibly reflecting a continuous antigenic stimulation in the professional setting. Keywords:SARS-CoV-2, vaccination, booster dose, healthcare workers, immune response, host factors, breakthrough infections == 1. Introduction == The newly emerged Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused an unprecedented global pandemic with more than 513 million confirmed cases and 6.2 million deaths by 1 May 2022. In Romania, as of 1 May 2022, there are more than 2.8 million confirmed cases and 65,000 deaths [1,2]. Most cases of COVID-19 are moderate to moderate, and those infected recover without specific treatment; however, severe disease can occur in various proportions, especially in the elderly and those with underlying medical conditions [3,4]. In addition, convalescent patients, irrespective of the clinical form of the acute infection, can experience persistent, variable symptomatology generally defined as long COVID-19, including newly diagnosed cardiovascular, metabolic, autoimmune, or neurologic diseases. As such, prevention measures are needed to reduce viral exposure. Healthcare workers (HCW) represent a particularly vulnerable group due to their essential role in patients care and their increased and continuous exposure to infection. Vaccination is usually a critical prophylaxis measure, aimed to ensure not only the safety of HCW and their patients, but also to interrupt the chains of viral transmission in the community [5]. As such, HCW were prioritized by most countries for vaccination at the beginning of 2021. The currently approved vaccines are highly efficient in protection against hospitalization and severe contamination; nevertheless, their efficacy seems to diminish over time, especially against symptomatic contamination and breakthrough infections in vaccinated people, including HCW. The humoral immune response to COVID-19 vaccines is usually influenced by Ac2-26 a large number of factors: previous COVID-19 infection, age, immunosuppression, type of vaccine, the number of doses received, and time since vaccination [5,6,7]. Longer intervals between the first and second dose of an mRNA vaccine correlate with stronger and more persistent immune responses [8]. Information regarding the duration of immunity after vaccination is not yet conclusive; it remains to be decided if a decrease in serum antibody levels can be used to indicate the degree of protection and the necessity of booster shots. It is hypothesized that protection is less influenced by waning antibody levels and instead is usually more dependent on the initial Ac2-26 immune response and the emergence of viral variants able to evade pre-existing immunity [9]. In previous studies of the dynamics of immune response in HCW six months after vaccination and/or contamination, we and other research groups reported that the best protection is usually conferred by vaccination in those with prior contamination, via the development Unc5b of persistent and more broadly neutralizing antibodies as well as stronger cellular immune responses compared to those elicited by a two-dose vaccination regimen only [10,11,12,13]. Medium- and long-term follow-ups of the kinetics of the Ac2-26 immune response after COVID-19 vaccination are necessary to predict the level of protection and adjust protective measures for different risk groups [5,6,7]. AIM:To evaluate the dynamics and persistence of the humoral immune response in healthcare workers one year after SARS-CoV-2 vaccination with an mRNA vaccine, and to examine the contribution of host factors that may influence the humoral immune response (gender, age, comorbidities, BMI, and previous SARS-CoV-2 contamination). == 2. Materials and Methods == == 2.1. Participant Selection and Data Collection == HCW from four hospitals in Bucharest, Romania (Victor Babes Hospital for Infectious and Tropical Diseases, University Emergency Hospital, Dr. Carol Davila Nephrology Clinical Hospital, and Stefan S. Nicolau Institute of Virology), volunteered to participate in this 12 month prospective longitudinal observational study to determine the dynamics of antibody levels after anti-COVID-19 vaccination. At the time of enrollment, all participants were vaccinated with two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech). Convenience sampling was used to select participants from designated hospitals. People were voluntarily enrolled in the study after receiving a complete package of information about the study and signing the informed.