Whereas individual use of antibody (Ab) tests has shown very limited value during the Covid-19 pandemic, population serological surveys have proven usefulness to characterize relevant epidemiological parameters and to guide public health strategies against COVID-19.1 As of October 2022, in the Valencian Community, Spain, with around five million inhabitants, 94% of the population aged 12 and over was fully vaccinated, and 58% had a booster vaccination administered (about 95% in the over 60s).2 Until that month, the Valencian Community had reported around 1.6 million SARS-CoV-2 infection cases (almost a third of the population),3 yet the cumulative incidence of infection may be underestimated due to the large proportion of asymptomatic people and the reduction in testing after the emergence of Omicron. A population serosurvey in April 2022 showed that at least 52% of the Valencian Community population had been infected.4

Few serosurvey studies involving the general population and extending into the Omicron BA.5 wave have been published.5,6 As a part of the ProVaVac Valencian COVID-19 vaccine research program launched by the Valencian Community Government in March 2021, we conducted a population-based study aimed primarily at estimating the seroprevalence of SARS-CoV-2 Ab in the general Valencian Community population in October 2022, when BA.5 was the predominant variant in Spain.

Of the weighted sample, 90.4% was vaccinated with at least one dose (see Table III in online Appendix). By age, all groups were above 90% except the 0-9 years old group (those under 6 were not candidates for vaccination). 59.2% of the weighted sample and more than 90% of people over 65 years had at least one booster dose. 30.6% of the weighted sample had a previous positive AIDT result registered on the MiVa Network, of which 8.1% had no detectable anti-N Ab.

Of the weighted sample, 98.4% maintained detectable RBD Ab against SARS-CoV-2, either due to vaccination or infection (Table 2). Even in the 0-9 age group, the proportion exceeds 90%. Of the weighted sample, 71% maintained detectable anti-N Ab, with higher figures in youngers (>80% between 10 and 34 years) than in those 65 and over (around 50%). When adding patients with at least one positive AIDT registered, 74.6% of the weighted sample had been infected at some point by SARS-CoV-2. 66.7% were Vac-Exp, 23.7% were Vac-Naïve and 7.9% were UnVac-Exp; the remaining 1.7% were UnVac-naïve, mostly people under 10 years.

As of October 2022, after the BA.1, BA.2 and BA.5 waves,3 three out of four people in the Valencian Community had been infected and two out of three had hybrid immunity, although less than one in three had a positive AIDT registered in the MiVa Network. Differences with the serosurvey of April 2022 (anti-N: 47.9%; Vac-exp: 51.9)4 indicate a high transmission during spring and summer 2022, when around 25% of the Valencian Community population became infected (see Table IV in online Appendix). These results are consistent with seroprevalence studies carried out after the BA.2 wave in British Columbia (Canada)5 and Geneva (Switzerland),6 with figures between 61% and 72% for anti-N seroprevalence.

Our study has some limitations. First, people who have been ordered a lab tested may be different from the general population in propensity to infection. Second, we excluded PCC with less than 7000 people assigned, excluding a good part of rural areas, although these usually organize blood drawn in other most populated villages. And third, precision in the pediatric population was markedly reduced by the low number of lab orders in younger groups.

In summary, by October 2022 around three quarters of the Valencian Community population had been infected with SARS-CoV-2 and, due to extensive vaccination, most exhibited hybrid immunity. The high proportion of hybrid immunity is relevant from a public health perspective since these people foreseeably have better and longer lasting protection against the development of severe COVID-19.9,10 The relatively low proportion of hybrid immunity among the elderly advised for a second vaccination booster in people 65 and over.

The datasets used in this article are not directly available due to Valencia Health Agency Resolution 2009/13312 (available at: http://www.san.gva.es/documents/152919/157920/resolucionsolicituddatos.pdf) which limits the cession of data to third parties without previous authorization from their Data Commission. Requests to access the data sets should be directed to Management Office of the Data Commission in the Valencia Health Department (email: solicitud_datos@gva.es; telephone numbers:+34 961-928207;+34 961-928198). Upon request, authors can get access to the databases to verify the accuracy of the analysis or the reproducibility of the study.

Miguel Ángel Negrín Hernández.

The corresponding author on behalf of the other authors guarantee the accuracy, transparency and honesty of the data and information contained in the study, that no relevant information has been omitted and that all discrepancies between authors have been adequately resolved and described.

S. Peiró, D. Navarro, H. Vanaclocha and R. Limón conceived and planned the study. A. García-Sempere, S. Peiró and D. Navarro drafted the study protocol (which was revised and approved by the ProVaVac Committee and the General Directorates of Health Care and Public Health of the Valencia Government Health Department). A. García-Sempere, H. Vanaclocha, R. Limón, D. Navarro and S. Peiró, prepared and coordinated the field work. D. Navarro and E. Giménez carried out the serologic and microbiological analyses. E. Giménez and H. Vanaclocha and linked the databases, and A. García-Sempere prepared the anonymized databases for analysis. A. García-Sempere and S. Peiró carried out the statistical analysis. A. García-Sempere, S. Peiró and D. Navarro drafted the first version of the manuscript with inputs from all authors (and several members of the ProVaVac Committee). All authors provided critical feedback and approved the final version submitted.

We are grateful to the staff and nurses of primary care centers participating in this study. We also thank Ana Berenguer, General Director of Analysis and Public Policies of the Presidency of the Valencia Government; Jorge Camacho and Eliseo Albert, from the Microbiology Service of the Valencia Clinic University Hospital; and José Sánchez-Payá, from the Alicante Institute for Health and Biomedical Research (ISABIAL). We also appreciate the contributions of the Valencian Vaccine Research Program (ProVaVac) group, during the preparation of the study protocol, the field work and the preparation of the final report of the study. The ProVaVac group, during the development of this study, was integrated by D.J. Burks (Príncipe Felipe Research Center, CIPF, Valencia, Spain); A. Cervantes, J. Redón and D. Navarro (INCLIVA Health Research Institute, Valencia, Spain); I. Comas (Biomedicine Institute of Valencia, Spanish Research Council, IBV-CSIC, València, Spain); J. Díez-Domingo, F. González-Candelas and S. Peiró (Foundation for the Promotion of Health and Biomedical Research of the Valencian Community, FISABIO, Valencia, Spain); C. Ferrer (Castelló Provincial Hospital Research Foundation, Castelló, Spain); I. Hernández (Miguel Hernandez University, Elx, Spain); R. Meneu (Health Services Research Institute Foundation, Valencia, Spain); N. Oliver (ELLIS Foundation, Alicante, Spain); J. Sánchez-Payá (Alicante Institute for Health and Biomedical Research, ISABIAL, Alicante, Spain); G. Sanz (Health Research Institute La Fe, València, Spain); J.M. Sempere (University of Alicante, Alicante, Spain); H. Vanaclocha (General Directorate of Public Health, Department of Health, Valencia Government, Valencia, Spain); and E. Zapater (Valencia General and University Hospital Research Foundation, Valencia, Spain).

Project funded by the Valencia Government Health Department and the EU Operational Program of the European Regional Development Fund (ERDF) for the Valencian Community 2014-2020, within the framework of the REACT-EU program, as the Union's response to the COVID-19 pandemic. A. García-Sempere was supported for this funding.

None.