Demographic and epidemiological information

From December 2022 to January 2023, during the first wave of the infection peak, 107 serum samples were collected from public health workers (adults) in Guangdong Provincial who had recovered 4 weeks after the first wave of the COVID-19 pandemic caused by Omicron BA.5. All participants were aged between 22 and 62, with a mean age of 43 years, including 44 males and 63 females. In July 2023, during the second wave of the COVID-19 epidemic caused by Omicron XBB.1.9 in Guangdong Province, 10 participants reported first or secondary infections. Their age ranged from 31 to 57 years, with a mean age of 33 years. Among these 10 participants, there was one male and nine females.

To investigate the differences in antibody levels among populations with different immunization history, the collected serum samples from the first wave of infection were divided into three groups: the primary vaccination group, the homologous booster vaccination group and the heterologous booster vaccination group. There were 4 individuals inoculated with less than 3 doses of inactivated vaccine in the primary immunization group, 91 individuals in the homologous booster vaccination group, and 12 individuals in the heterologous booster vaccination group, which were vaccinated with recombinant novel SARS-CoV-2 vaccines (Fig. 1). In the subsequent waves, there were 3 individuals in the primary immunization group, 4 individuals in the homologous booster vaccination group, and 5 individuals in the heterologous booster vaccination group.

Fig. 1

Neutralization experiment results of seven SARS-CoV-2 variants during the first wave of the COVID-19 epidemic: (A) Neutralizing antibody levels of all samples; (B) Neutralizing antibody levels of the primary vaccination group; (C) Neutralizing antibody level of the homologous booster group; (D) Neutralizing antibody levels of the heterologous booster group

NAb titers in serum for the first wave infection against Omicron variants

For the serum samples from thee first wave of infection participants, we found that the NAb titers were significantly decreased against prototype SARS-CoV-2 compared to Omicron variants BA.5, BQ.1, XBB.1.1, XBB.1.16, XBB.1.9 and EG.5. The highest geometric mean titer (GMT) of the samples against the prototype was 280, and the GMT for BA.5 was 41 (5.80 fold, P < 0.001), XBB.1.16 was 14 (19.18 fold, P < 0.001), XBB.1.9 was 11 (23.83 fold, P < 0.001), BQ.1, XBB 1.1 and EG.5 were only 8 (BQ.1, 35.86 fold, P < 0.001; XBB.1.1, 32.67 fold, P < 0.001; EG.5, 35.62 fold, P < 0.001) (Fig. 1A).

Among the primary vaccination, homologous booster vaccination and heterologous booster vaccination group, the highest geometric mean titer (GMT) in all three groups was higher against the prototype than that for BA.5, BQ.1, XBB.1.1, XBB.1.16, XBB.1.9 and EG.5 (Fig. 1B-D). In the primary vaccination group, only one serum sample had a higher titer of neutralizing antibodies against BQ.1 than BA.5. The GMT dropped from 152 for the prototype to 38 for BA.5 (2.99 fold, P = 0.343), 11 for BQ.1 and XBB.1.9 (12.44 fold, P = 0.143), 8 for XBB.1.1 (18.00 fold, P = 0.057), 16 for XBB.1.16 (8.50 fold, P = 0.143), and 13 for EG.5 (10.30 fold, P = 0.143) (Fig. 1B). In the homologous booster vaccination group, the GMT dropped from 287 for the prototype to 45 for BA.5 (5.41 fold, P < 0.001), 15 for XBB.1.16 (18.65 fold, P < 0.001), 12 for XBB.1.9 (23.51 fold, P < 0.001), and 8 for BQ.1, XBB.1.1 and EG.5 (BQ.1, 36.55 fold, P < 0.001; XBB.1.1, 33.53 fold, P < 0.001; EG.5, 35.43 fold, P < 0.001)(Fig. 1C). In the heterologous booster vaccination group, the GMT dropped from 287 for the prototype to 23 for BA.5 (11.68 fold, P < 0.001), 6 for BQ.1 (44.20 fold, P < 0.001), 8 for XBB.1.1 and XBB.1.9 (32.86 fold, P < 0.001), 9 for XBB.1.16 (30.96 fold, P < 0.001), and 5 for EG.5 (55.95 fold, P < 0.001) (Fig. 1D). Notably, participants from the homologous booster vaccination group had the same neutralizing antibodies titers against BA.5 and BQ.1.

NAb titers in serum for the subsequent waves infection against Omicron variants

For the serum samples from the subsequent waves of infection participants, we found that the GMT of the samples against the prototype was 362, and the GMT for BA.5 was 119 (2.03 fold, P < 0.05), BQ.1 was 181 (1.00 fold, P = 0.121), XBB.1.1 was 104 (2.48 fold, P < 0.05), XBB.1.16 was 79 (3.59 fold, P < 0.01), XBB.1.9 was 69, and EG.5 was 64 (XBB.1.9, 4.28 fold, P < 0.01; EG.5, 4.66 fold, P < 0.01) (Fig. 2).

Fig. 2

Neutralizing antibody levels of 10 participants during the second wave of the COVID-19 epidemic

Magnetic particle chemiluminescence

In addition, the IgG antibody in the serum was detected using a commercial SARS-CoV-2 IgG antibody test kit. The positive rate of IgG antibody was 98.13% (105/107) during the second wave of the COVID-19 epidemic. The median of IgG antibody level was 130.12 (Fig. 3A). The median of IgG antibody level in the homologous booster vaccination group was the highest, at 131.52, followed by the heterologous booster vaccination group, with a median of 127.91, and the primary vacancy group, with a median of 79.72. There was a positive correlation between the IgG antibody level and the GMT against the prototype virus (rs=0.732, P < 0.001).

Fig. 3

Immune status of the population during the first and second waves of the COVID-19 epidemic: (A) IgG antibody levels of 107 participants during the second wave of the COVID-19 epidemic; (B) IgG antibody levels of 10 participants during the second wave of the COVID-19 epidemic

During the second wave of COVID-19 epidemic, the IgG antibody of all participants was detected as positive (10/10), with a median IgG antibody level of 235.09 (Fig. 3B). There was a positive correlation between the IgG antibody level and the GMT against the prototype virus (rs=0.748, P = 0.013).