■分析接种或未接种皮内卡介苗(BCG)的COVID-19康复成人血浆对人巨噬细胞的干扰作用。
■BATTLE临床试验(NCT04369794)是在2020年SARS-CoV-2大流行中启动的,目的是研究COVID-19康复成人卡介苗再接种的安全性和有效性。我们测量了在基线和干预后45天,从22名接种BCG的患者和17名安慰剂患者的血浆中培养的人巨噬细胞中11种COVID-19相关基因的表达诱导。亚组分析基于性别,年龄,工作类型(医护人员[HCW]与非HCW),以及嗅觉缺失/味觉障碍的存在。
■与安慰剂对应的血浆相比,接种BCG的患者的血浆增加了人巨噬细胞中干扰素(IFN)β-1b的表达诱导(p=0.042)。这种增加在女性和医护人员(HCW)中更为明显(分别为p=0.007和0.001)。干扰素诱导的跨膜蛋白3(IFITM3)的表达诱导由来自接种BCG的女性的血浆增加,年轻年龄组,和HCWs(分别为p=0.004、0.011和0.040)。年轻BCG受体的血浆增加了白细胞介素(IL)-10的诱导(p=0.008)。非HCWBCG受体血浆诱导IL-6表达增加,但HCWBCG受体血浆诱导IL-6表达减少(p=0.005)。与没有症状的患者相比,入院时出现无嗅觉/味觉障碍的患者的基线血浆诱导的血管紧张素转换酶2(ACE2)降低(0.76vs0.97,p=0.004)。如果BCG接受者在入院时出现嗅觉缺失/味觉障碍,则其血浆对ACE2的表达诱导显着增加(p=0.028)。
■IFNβ-1b的表达式,与COVID-19恢复期患者血浆孵育的人巨噬细胞中的IFITM3、IL-6和IL-10受卡介苗调节。这些调制取决于特定主题的特征,包括性别,年龄,临床表现(失语症/味觉障碍),作业类型,和之前接触过分枝杆菌。
UNASSIGNED: To analyze the interfering effect of plasma from COVID-19 convalescent adults vaccinated or not with intradermal Bacillus Calmette-Guérin (BCG) on human macrophages.
UNASSIGNED: The BATTLE clinical trial (NCT04369794) was initiated in the 2020 SARS-CoV-2 pandemic to study the safety and efficacy of BCG revaccination of COVID-19 convalescent adults. We measured the expression induction of eleven COVID-19-related genes in human macrophages cultured in plasma taken from 22 BCG vaccinated and 17 placebo patients at baseline and 45 days post-intervention. Subgroup analysis was based on gender, age, job type (healthcare worker [HCW] vs non-HCW), and the presence of anosmia/dysgeusia.
UNASSIGNED: Compared to plasma from placebo counterparts, the plasma of BCG vaccinated patients increased the expression induction of interferon (IFN)β-1b (p = 0.042) in human macrophages. This increase was more pronounced in females and in healthcare workers (HCW) (p = 0.007 and 0.001, respectively). Interferon-induced transmembrane protein 3 (IFITM3) expression induction was increased by plasma from BCG vaccinated females, young age group, and HCWs (p = 0.004, 0.011, and 0.040, respectively). Interleukin (IL)-10 induction increased by the plasma of young BCG recipients (p = 0.008). Induction of IL-6 expression increased by non-HCW BCG recipients plasma but decreased by HCW BCG recipients plasma (p = 0.005). Baseline plasma of patients who presented with anosmia/dysgeusia at the time of admission induced lower angiotensin-converting enzyme 2 (ACE2) compared to those without the symptom (0.76 vs 0.97, p = 0.004). ACE2 expression induction significantly increased by plasma of BCG recipients if they had anosmia/dysgeusia on admission (p = 0.028).
UNASSIGNED: The expressions of IFNβ-1b, IFITM3, IL-6, and IL-10 in human macrophages incubated with the plasma of COVID-19 convalescent patients were modulated by BCG. These modulations depended on subject-specific characteristics, including gender, age, clinical presentation (anosmia/dysgeusia), job type, and previous exposure to mycobacteria.