Publication date: Jun 03, 2025

We have previously reported on natural humoral immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a Norwegian cohort between 2020 and 2021. In this study, we evaluated long-term humoral (including vaccination-induced) immunity in the same cohort and assessed predictors of high antibody levels against spike protein, as well as the persistence of antibodies against the virus spike and nucleocapsid proteins. Vaccination data and antibody levels against the spike and nucleocapsid proteins were collected at 12 (only in infected participants) and 24 months (in both infected and uninfected participants) after the participants’ first polymerase chain reaction (PCR) tests for the virus. Antibody levels against spike protein at 24 months were categorized as high or low based on the 50th percentile. Possible predictors of high antibody levels against spike protein were examined using univariate and multivariate logistic regression models. Of 1119 original participants (400 PCR + and 719 PCR -), 574 responded to our questionnaires and were invited to antibody measurements (median age: 51 years; women: 59%). Vaccination data showed that 11% were fully immunized, and 85% were booster-immunized at 24 months. Antibody levels were evaluated in 72% (287/400) of the PCR + participants at 12 months and 58% (233/400) at 24 months. At 12 and 24 months, we observed that 97% (278/287) and 100% (233/233), respectively, still had antibodies against the spike protein, and 86% (248/287) and 95% (221/233), respectively, against the nucleocapsid protein. Antibody levels were also evaluated in 34% (247/719) of those in the PCR - group, which revealed that 99. 5% and 69% had detectable antibodies against spike and nucleocapsid proteins, respectively, at 24 months. Irrespective of pre-vaccination SARS-CoV-2 infection status, the booster-immunized participants were 3. 7 cD7 more likely to have high antibody levels against spike protein vs the non-booster-immunized ones. Those aged > 60 years had the highest median antibody levels against the spike protein and were more likely to be booster-immunized. Our findings highlight the benefits of booster vaccinations for humoral immune responses. Long-term antibody levels against the SARS-CoV-2 spike protein were higher in booster-immunized participants vs the non-booster-immunized, irrespective of pre-vaccination infection status. 146,469: The COVID-19 study in Telemark and Agder-COVITA. gov ID: NCT04514003.

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