Immune response to and virological profile of SARS-CoV-2 before and after symptom onset in individuals vaccinated with inactivated COVID-19 vaccines

Abstract

China encountered a COVID-19 pandemic shortly after lifting the zero-COVID-19 policy in December 2022. We prospectively investigated the immune responses to SARS-CoV-2 before and after symptom onset of breakthrough infection in individuals vaccinated with inactivated COVID-19 vaccines. Blood samples from 35 vaccinated participants were collected from December 16 to 20, 2022 when they had no symptoms and a second blood sample was collected from each participant from January 4 to 6, 2023. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgG and IgM, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured with commercially available kits respectively. During a period of average 17.0 (±1.6) days, 30 (85.7%) of 35 participants developed toxemia and respiratory symptoms and 34 (97.1%) were defined with SARS-CoV-2 infection based on positive SARS-CoV-2 RNA in pharyngeal swabs (32) and rising titers of anti-SARS-CoV-2 IgG (34). Before symptom onset, 16 (47.1%), 13 (38.2%), and 5 (14.7%) of the infected individuals already had relatively high anti-SARS-CoV-2 IgG titers, elevated IL-6 and CRP respectively. After 17.0 (±1.6) days, the median anti-SARS-CoV-2 IgG level was significantly increased (46.85 vs 359.45 AU/mL, p < .001), whereas the proportions of elevated IL-6 and CRP were each remarkably reduced. None of the participants infected with SARS-CoV-2 had detectable anti-SARS-CoV-2 IgM. In vaccinated individuals infected with SARS-CoV-2, specific anamnestic immune responses may initiate before symptom onset and robust immune response may develop in very early phase, which should be a critical mechanism to lessen the severity of COVID-19 and reduce the mortality by COVID-19 vaccination.

Keywords: COVID-19 vaccine; anamnestic immune responses; before symptom onset; brisk initiation; vaccinated individual.

Figure 1.

Levels of anti-SARS-CoV-2 IgG (a) and IgM (b) in 35 subjects before symptom onset and after 17 days. The first blood sample was collected at a median 2 days (range 1–8) before symptom onset, and the second blood was collected after average 17 (±1.6) days. All samples were tested for the antibodies once at same time. Based on the manufacturer’s instructions, a value ≥ 10.0 arbitrary units (AU)/mL was positive and that < 10.0 AU/mL was negative for both IgG and IgM.

Figure 2.

Analysis of anti-SARS-CoV-2 IgG in 34 subjects infected with SARS-CoV-2. Blood sampling information is same as that in legend to Figure 1. (a) thirty-four subjects infected with SARS-CoV-2 were divided into four groups, I (5), II (11), III (15), and IV (3), based on the pre-symptom anti-SARS-CoV-2 IgG levels ≥ 100.0, 50–99.9, 10–49.9, and < 10 arbitrary units (AU)/mL respectively. (b) levels of anti-SARS-CoV-2 IgG among four group before symptom onset had statistical significance (Z = 28.946, p < .001), but those after 17 (±1.6) days were comparable (Z = 4.190, p = .242). The increased Fold had statistical difference among four groups (Z = 28.428, p < .001), and the higher pre-symptom IgG levels, the fewer increased folds.

Figure 3.

Analysis of interleukin-6 (IL-6) and C reactive protein (CRP) in 34 subjects infected with SARS-CoV-2. Blood sampling information is same as that in legend to Figure 1. The reference intervals for IL-6 and CRP are <7 pg/mL and <6 μg/mL respectively. (a) proportion of elevated IL-6 before symptom onset and after 17 (±1.6) days. (b) proportion of elevated CRP before symptom onset and after 17 (±1.6) days.