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Background: Heterogeneity of the population in relation to infection, COVID-19 vaccination, and host characteristics is likely reflected in the underlying SARS-CoV-2 antibody responses. Methods: We measured IgM, IgA, and IgG levels against SARS-CoV-2 spike and nucleocapsid antigens in 1076 adults of a cohort study in Catalonia between June and November 2020 and a second time between May and July 2021. Questionnaire data and electronic health records on vaccination and COVID-19 testing were available in both periods. Data on several lifestyle, health-related, and sociodemographic characteristics were also available. Results: Antibody seroreversion occurred in 35.8% of the 64 participants non-vaccinated and infected almost a year ago and was related to asymptomatic infection, age above 60 years, and smoking. Moreover, the analysis on kinetics revealed that among all responses, IgG RBD, IgA RBD, and IgG S2 decreased less within 1 year after infection. Among vaccinated, 2.1% did not present antibodies at the time of testing and approximately 1% had breakthrough infections post-vaccination. In the post-vaccination era, IgM responses and those against nucleoprotein were much less prevalent. In previously infected individuals, vaccination boosted the immune response and there was a slight but statistically significant increase in responses after a 2nd compared to the 1st dose. Infected vaccinated participants had superior antibody levels across time compared to naïve-vaccinated people. mRNA vaccines and, particularly the Spikevax, induced higher antibodies after 1st and 2nd doses compared to Vaxzevria or Janssen COVID-19 vaccines. In multivariable regression analyses, antibody responses after vaccination were predicted by the type of vaccine, infection age, sex, smoking, and mental and cardiovascular diseases. Conclusions: Our data support that infected people would benefit from vaccination. Results also indicate that hybrid immunity results in superior antibody responses and infection-naïve people would need a booster dose earlier than previously infected people. Mental diseases are associated with less efficient responses to vaccination. This work was funded by Incentius a l’Avaluació de Centres CERCA (in_CERCA); EIT HEALTH BP2020-20873-Certify.Health.; Fundació Privada Daniel Bravo Andreu; PID2019-110810RB-I00 grant (Spanish Ministry of Science & Innovation). Rocio Rubio had the support of the Health Department, Catalan Government (PERIS SLT017/20/000224). E.P. was supported by a grant from the Junta de Andalucía/EU. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S). ISGlobal and IGTP receive support from the Generalitat de Catalunya through the CERCA Program. GCAT was funded by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026) and have additional suport by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529), National Grant PI18/01512 and VEIS project (001-P-001647) (co-funded by European Regional Development Fund (ERDF), “A way to build Europe”).