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探讨 COVID-19 疾病在妊娠期间引发的炎症反应特征。

Characterization of the inflammatory response to COVID-19 illness in pregnancy.

机构信息

Johns Hopkins University, Department of Gynecology and Obstetrics, Baltimore, MD, United States.

Johns Hopkins University, Department of Gynecology and Obstetrics, Baltimore, MD, United States.

出版信息

Cytokine. 2023 Oct;170:156319. doi: 10.1016/j.cyto.2023.156319. Epub 2023 Aug 4.

DOI:10.1016/j.cyto.2023.156319
PMID:37544133
Abstract

OBJECTIVE

Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1β, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease.

STUDY DESIGN

This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1β, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test.

RESULTS AND DISCUSSION

We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1β, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness.

摘要

目的

与非妊娠同龄人相比,感染 COVID-19 的孕妇面临更大的发病率和死亡率。先前在非妊娠患者中的研究表明,重症监护病房中 SARS-CoV-2 阳性患者的临床预后不良与促炎标志物白细胞介素 (IL)-1β、IL-6、IL-8 和 IL-10 的显著增加有关。重要的是,这些炎症标志物的高水平也与不良妊娠结局相关,包括自发性早产、子痫前期和严重呼吸道疾病。

研究设计

这是一项回顾性队列研究,比较了急性/亚急性 SARS-CoV-2 感染孕妇与既往暴露孕妇的血清炎症细胞因子谱。两个队列中的所有受试者均检测出 SARS-CoV-2 抗体阳性;然而,急性/亚急性感染队列中的患者在血清样本采集后 30 天内有记录的 SARS-CoV-2 逆转录聚合酶链反应 (RT-PCR) 结果阳性。血清样本是在妊娠 13 至 39 周期间通过产前静脉穿刺获得的,队列是根据胎龄匹配的。使用标准 ELISA 测定法从母体血清中测定干扰素 (IFN)-γ、IL-10、IL-1β、IL-4、IL-6、IL-8 和肿瘤坏死因子 (TNF)-α,使用 Mann-Whitney 检验比较中位数细胞因子浓度。

结果与讨论

我们招募了 50 名在佐治亚州亚特兰大的 Grady 纪念医院接受产前护理的非西班牙裔黑人确诊 COVID-19 感染患者。急性/亚急性感染组(n=22)的 SARS-CoV-2 抗体、IL-10、IL-1β 和 IL-8 浓度显著较高,而既往暴露组(n=28)的 IL-4 浓度显著较高。两组间的医疗合并症无显著差异。与既往暴露相比,急性/亚急性 SARS-CoV-2 感染的孕妇血清中促炎细胞因子浓度显著升高,提示与非妊娠人群一样,SARS-CoV-2 感染会改变妊娠期间循环促炎标志物的水平。细胞因子水平的升高可能导致 COVID-19 疾病观察到的不良产科结局。

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