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Hum Vaccin Immunother . Seroprevalence and determinants of SARS-CoV-2 anti-nucleocapsid IgG in a vaccinated Iranian adult population: A cross-sectio

tetano

Editor, Senior Moderator
Hum Vaccin Immunother


. 2025 Dec;21(1):2560063.
doi: 10.1080/21645515.2025.2560063. Epub 2025 Sep 17. Seroprevalence and determinants of SARS-CoV-2 anti-nucleocapsid IgG in a vaccinated Iranian adult population: A cross-sectional study, Summer 2023

Alireza Yeganeh[SUP] 1 [/SUP], Ebrahim Kalantar[SUP] 2 [/SUP], Abdollah Ghaffari[SUP] 2 [/SUP], Aliasghar Keramatinia[SUP] 3 [/SUP], Farshid Yeganeh[SUP] 4 [/SUP]



Affiliations
Abstract

Anti-nucleocapsid (anti-N) IgG serology is increasingly used to distinguish natural SARS-CoV-2 infection from vaccine-induced immunity. However, post-vaccination seroepidemiological data from highly immunized Middle Eastern populations remain limited. We assessed anti-N IgG seroprevalence and its predictors in a cohort of Iranian adults during the summer of 2023. A total of 251 individuals aged 18-65 years were enrolled through community outreach at Gholhak Laboratory, a high-throughput diagnostic center in Tehran. Participants completed structured questionnaires that captured demographic characteristics, COVID-19 vaccination history (vaccine platform, dose count, and time since last dose), smoking status, occupation, pregnancy status, and prior COVID-19-related hospitalization. Anti-N IgG levels were measured using a commercial ELISA (Pishtaz Teb, Tehran, Iran); seropositivity was defined by a signal-to-cutoff ratio ≥ 1.1. Prevalence ratios (PRs) were estimated via Poisson regression with robust variance, adjusting for covariates including age, gender, BMI, smoking, and vaccination characteristics. The overall anti-N seroprevalence was 55.8% (95% CI: 49.7-61.7). Seropositivity was significantly associated with female gender (PR for males 0.70, p = .002), older age (3% higher per decade, p = .017), and nonsmoking status (PR for smokers 0.70, p = .008). No associations were observed with vaccine platform, dose count, or recency. Sensitivity analyses using alternative ELISA classifications and penalized regression yielded similar results. Despite near-universal vaccination, more than half of the participants exhibited serological evidence of past infection. These findings suggest that additional in this urban Iranian setting, additional booster doses may offer limited additional protection against infection and underscore the influence of gender, age, and smoking on natural infection risk.

Keywords: COVID-19 vaccine; Iran; SARS-CoV-2; anti-nucleocapsid antibody; natural infection; seroprevalence.

 
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