A trend analysis of Sars-Cov-2 anti nucleocapsid IgG antibodies with a recommendation of the cut-off classification to identify naïve, vaccinated, and infected cases

Determination of the vaccination’s effect on immune responses with the emergence of the Sars-Cov-2 pandemic become an important issue. This study aimed to evaluate the response of the anti-nucleocapsid IgG (anti-N IgG) index in naïve, vaccinated, or infected cases, in addition to suggesting ‘How to distinguish between vaccinated versus infected cases via anti-N IgG?’. Anti-N levels of the naïve [0.03 (0.02–0.06)], vaccinated [0.7 (0.2–1.96)], and infected [3.07 (1.44–5.2)] groups were statistically different (p<0.0001). Anti-N levels were statistically different in all periods of the infected and vaccinated sub-groups (p<0.0001). An inter-group analysis of the cases with repeated tests established that there was no difference between the not-vaccinated (-1.44±1.27) and after-infection early-vaccinated (-1.62±0.93) groups (p=0.717). A significant difference was observed between the after-infection early-vaccinated (-1.62±0.93) and late-vaccinated groups (1.5±1.61) (p<0.0001). Three-category cut-off levels were calculated for the naive, vaccinated, and infected cases as ≤0.32, 0.32–1.40, and ≥1.40 respectively. The area under the receiver operating curve (AUROC) of this classification was 0.907 (95% CI, 0.879–0.930) and the AUROC of the manufacturer’s cut-off (≥1.40) was 0.790 (95% CI, 0.754–0.823) (p<0.0001). This study demonstrates that early vaccination after the infection does not affect the trend of the anti-N level. The manufacturers should set out to update their tests dating back to the pre-vaccine period for the post-vaccine period.

Keywords: COVID-19, anti-nucleocapsid IgG, ınactive vaccine, naïve, SARS-Cov-2, vaccination, serology