Shapiro Janna R, Seddu Kumba, Park Han-Sol, Lee John S, Creisher Patrick S, Yin Anna, Shea Patrick, Kuo Helen, Li Huifen, Abrams Engle, Leng Sean X, Morgan Rosemary, Klein Sabra L
Johns Hopkins Bloomberg School of Public Health.
Johns Hopkins University School of Medicine.
Res Sq. 2023 Feb 8:rs.3.rs-2557775. doi: 10.21203/rs.3.rs-2557775/v1.
Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.
背景 对于包括流感疫苗和新冠疫苗在内的多种疫苗，女性接种后报告的不良事件（AE）比男性更多。这种差异通常被认为是报告偏差，但生物性别和社会性别各自的相对影响却鲜为人知。我们通过在接种疫苗后5 - 8天使用不良事件调查问卷，研究了性别和社会性别在老年人（≥75岁）接种高剂量季节性流感疫苗后不良事件发生率中的作用。参与者的性别（男性或女性）通过自我报告确定，并使用一份社会性别评分问卷将参与者分配到四个社会性别类别之一（女性化、男性化、双性化或未分化）。在接种疫苗前采集的血浆样本中测量了性类固醇激素和炎性细胞因子，以阐明所报告不良事件可能的生物学机制。结果 在四个流感季节（2019 - 2022年），共对173名参与者接种了423剂疫苗，其中339剂疫苗（2020 - 2022年）有社会性别数据。105剂疫苗（25%）接种后报告了至少一次不良事件，涉及23名男性和82名女性。大多数不良事件发生在注射部位，症状轻微且为一过性。女性发生不良事件的几率是男性的3倍，并且女性随年龄下降的幅度比男性更大。然而，社会性别效应无统计学意义，这支持了生物性别在不良事件发生中起核心作用的观点。在男性中，雌二醇与白细胞介素 - 6以及发生不良事件的概率显著相关。在女性中这两种关联均不存在，提示雌二醇对不良事件发生有性别特异性影响，这支持了生物性别差异的发现。结论 这些数据支持在老年人流感疫苗接种后不良事件的发生中，生物性别比社会性别起更大作用，并初步研究了可能介导这种性别差异的激素机制。本研究凸显了测量社会性别所面临的复杂性，以及分别评估男性和女性不良事件对于更好理解如何针对不同人群亚组调整疫苗接种策略的重要性。
