Clinical characteristics and antibody responses to Omicron variants among pregnant women in China during the December 2022-April 2023 COVID-19 pandemic wave.

BACKGROUND: Clinical characteristics and humoral immune responses in pregnant women following natural SARS-CoV-2 Omicron infection remain unclear, particularly in those previously receiving inactivated vaccines, which may induce immune imprinting and affect cross-neutralization against emerging Omicron subvariants. METHODS: This cross-sectional investigation was conducted in Zhejiang Province between December 2022 and April 2023. A total of 223 pregnant women with a gestational age of at least six weeks and 31 healthy non-pregnant women were recruited as research subjects and controls. Serum specimens were collected to determine anti-RBD IgG levels by ELISA, alongside pseudovirus neutralizing antibody titers against the prototype strain and Omicron BA.4/5, XBB.1.5 subvariants. Relevant clinical information was gathered through questionnaires, and multivariate regression analysis was applied to identify influencing factors of immune response characteristics. RESULTS: Acute COVID-19 symptom profiles were comparable between pregnant women and non-pregnant healthy women (P > 0.05). Among questionnaire respondents, pregnant individuals had markedly prolonged symptom recovery, with a notably higher proportion taking over one week to recover (73.0% vs. 23.1%, P = 0.045), and presented a significantly higher medical consultation rate (73.0% vs. 15.4%, P < 0.001). For immune response, neutralizing antibody levels against the Omicron BA.4/5 showed no intergroup difference overall. By contrast, pregnant women exhibited significantly lower XBB.1.5 neutralizing antibody titers than controls, with geometric mean titers of 16.35 and 45.96 respectively (P < 0.05). Multivariate regression analysis indicated that SARS-CoV-2 infection during the Omicron epidemic was the major independent factor linked to elevated neutralizing antibody levels, while a BMI below 25.0 kg/m² was independently correlated with higher XBB.1.5 neutralizing antibody titers. Additionally, no significant differences in clinical manifestations or immune responses were found among women in different trimesters of pregnancy. CONCLUSION: In vaccine-primed pregnant women with natural Omicron infection, acute clinical manifestations and homologous humoral immunity against BA.4/5 were similar to non-pregnant controls, but symptom recovery was prolonged and cross-neutralization against XBB.1.5 was reduced. No trimester-specific differences were observed.