Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

Abstract

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4⁺ and CD8⁺ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7-55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, -0.52; p < 0.001) but not in VAC-ex (rho -0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity.

Keywords: SARS-CoV-2; T cells; cumulative incidence of SARS-CoV-2 infection; neutralizing antibodies; seroprevalence.

Figure 1

SARS‐CoV‐2‐receptor binding domain (RBD) total antibodies (in BAU/ml) in participants. (A) Box Whisker plots depicting serum antibody levels according to vaccination and SARS‐CoV‐2 infection status at time of recruitment. (B) Box Whisker plots depicting serum antibody levels in vaccinated/SARS‐CoV‐2‐experienced and vaccinated/SARS‐CoV‐2‐naïve participants by number of vaccine doses received. (C) Serum antibody levels in vaccinated/SARS‐CoV‐2‐experienced and vaccinated/SARS‐CoV‐2‐naïve receiving one or more booster doses by booster type (homologous vs. heterologous). p‐values for statistical comparisons are shown where appropriate.

Figure 2

SARS‐CoV‐2‐receptor binding domain (RBD) total antibodies (in BAU/ml) in vaccinated/SARS‐CoV‐2‐experienced (A) and vaccinated/SARS‐CoV‐2‐naïve (B) participants according to the vaccination schedule (full vaccination with no booster dose, homologous booster dose and heterologous booster dose) and time elapsed since last vaccine dose.

Figure 3

SARS‐CoV‐2‐receptor binding domain (RBD) total antibodies (in BAU/ml) in vaccinated/SARS‐CoV‐2 experienced participants with a history of a positive active infection diagnostic test (AIDT) according to time elapsed since documentation of the positive result and time since last vaccine dose.

Figure 4

Serum neutralizing antibody titers (reciprocal IC₅₀) against SARS‐CoV‐2 Wuhan‐Hu‐1, Omicron BA.1 and BA.2 (sub)variants in vaccinated/SARS‐CoV‐2 experienced, vaccinated/SARS‐CoV‐2 naïve participants and unvaccinated/SARS‐CoV‐2 experienced participants. Vaccinated/experienced, vaccinated/naïve and nonvaccinated/experienced participants were matched for sex and age, and vaccinated participants for booster type. Nevertheless, time since last vaccine dose was significantly shorter (p < 0.001) in vaccinated/naïve than in vaccinated/experienced participants (median 116 days; range, 29–298; vs. 162 days; range, 0–308). p‐values for statistical comparisons are shown.

Figure 5

Frequency of SARS‐CoV‐2‐Spike(S)‐reactive IFN‐ γ‐producing CD4⁺ and CD8⁺ T cells in vaccinated/SARS‐CoV‐2 experienced, vaccinated/SARS‐CoV‐2 naïve participants, unvaccinated/SARS‐CoV‐2 experienced and unvaccinated/SARS‐CoV‐2 naïve participants. Vaccinated/experienced, vaccinated/naïve and unvaccinated/experienced participants were balanced for sex and age, and for vaccinated individuals for booster type; nevertheless, time since last vaccine dose was significantly lower (p < 0.001) in vaccinated/naïve than in vaccinated/experienced participants (median 113 days; range, 0–298; vs. 175 days; range, 0–308).