Analyzing the diffusion and duration of antibodies to SARS-CoV-2 during the natural infection and comparison with vaccination

Abstract

To monitor SARS-CoV-2 diffusion, we measured anti-Spike S1/S2 IgGs in the serum of nearly 4000 workers employed in several healthcare facilities for one year. We found that the antibody response persists at least over 8 months in symptomatic subjects, particularly in individuals with anosmia/dysgeusia. Moreover, analyzing a smaller cohort (124 healthcare employees of which 57 had a previous history of SARS-CoV-2 exposure) vaccinated with two doses of Comirnaty vaccine, we observed that in symptomatic subjects previously exposed to SARS-CoV-2 one dose vaccine was sufficient to stimulate very high levels of antibodies, suggesting that these subjects should take only one dose of vaccine.

Fig. 1

Distribution of IgG positivity across different geographical areas and healthcare facilities in Lombardy, Italy. Employees from seven different healthcare facilities were analyzed for their anti-SARS-CoV-2 IgG positivity. Pie charts show the percentage of negative subjects (IgG < 12 AU/mL) (orange) and that of positive subjects (IgG ≥ 12 AU/mL) (blue) in each healthcare facility: Istituto Clinico Humanitas (ICH), Rozzano (MI); Humanitas Gavazzeni, Bergamo; Humanitas Castelli, Bergamo; Humanitas Mater Domini (HMD), Castellanza (VA); Humanitas Medical Center (HMC), Varese (VA); Humanitas University (HU), Pieve Emanuele (MI); Humanitas San Pio X, Milan, (MI). Percentage of positive subjects are indicated

Fig. 2

Frequency of IgG positivity (IgG ≥ 12 AU/mL) by sex and age. Histograms show the percentage of positive individuals (IgG ≥ 12 AU/mL) divided by age range and sex on the whole population regardless of healthcare facility (20–30: M, n = 22; F = 88; 31–40: M, n = 31; F, n = 114; 41–50: M, n = 53; F, n = 108; 51–60: M, n = 26; F, n = 56; > 60: M, n = 19; F, n = 6); p values were determined using Cuzick’s test for trend. p = 0.0374 (total); p = 0.0008 (female); p = 0.1498 (male); p = 0.0024 (interaction)

Fig. 3

Anti-Spike S1/S2 IgG serum levels over phases 1, 2 and 3. Anti-Spike S1/S2 IgG serum levels were measured in asymptomatics (n = 61), paucisymptomatics (n = 163), and symptomatics (n = 275) at three different time points (phase 1–3). The box plots show the interquartile range, the horizontal lines show the median values, and the whiskers indicate the minimum-to-maximum range. Log scale on y-axis. P values were measured using a one-tailed Wilcoxon matched-pairs signed rank test

Fig. 4

Exponential increase of anti-Spike 1/2 IgGs after the first dose of Comirnaty vaccine in SARS-Cov-2 exposed individuals. Anti-Spike 1/2 IgG serum levels in naïve (not previously exposed to SARS-CoV-2) (n = 64) and SARS-CoV-2 exposed individuals (n = 36) measured before vaccination (Before VAX), at around 17 days from the first dose of vaccine (Post Dose 1) and 11 days after the second dose (Post Dose 2). Spaghetti plot showing the trends for each individual subject by linked dots. Log scale on y-axis. P values were determined using Friedman test with Dunnett's multiple comparisons test

Fig. 5

Symptomatic subjects show higher increase of anti-Spike 1/2 IgG levels after both doses of vaccine compared to asymptomatic/paucisymptomatic individuals. Anti-Spike 1/2 IgG serum levels in asymptomatics/paucisymptomatics (A-/Paucisympt) (n = 15) or symptomatics (Sympt) (n = 42) at around 17 days after the first (a) or 11 days after the second dose of vaccine (A-/Paucisympt n = 14, Sympt n = 33) (b). Each dot corresponds to an individual subject. Log scale on y-axis. The box plots show the interquartile range, the horizontal lines show the median values and the whiskers indicate the minimum-to-maximum range. P values were determined using two-tailed unpaired Kolmogorov–Smirnov test