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COVID-19 患者和 ChAdOx1 nCoV-19(AZD1222)疫苗接种者中的炎症和细胞毒性介质。

Inflammatory and cytotoxic mediators in COVID-19 patients and in ChAdOx1 nCoV-19 (AZD1222) vaccine recipients.

机构信息

Laboratório das Interações Vírus-Hospedeiros (LIVH), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, Brazil.

Rede Casa Hospital Rio Laranjeiras e Rio Botafogo, Rio de Janeiro 22240-000, Brazil.

出版信息

Cytokine. 2023 Nov;171:156350. doi: 10.1016/j.cyto.2023.156350. Epub 2023 Sep 4.

DOI:10.1016/j.cyto.2023.156350
PMID:37672863
Abstract

Immunological and cytotoxic mediators are induced in natural infection and are essential for the effectiveness of vaccination. Vaccination is useful to prevent the spread of SARS-CoV-2 and limit the morbidity/mortality of COVID-19. ChAdOx1 nCoV-19 is one of the most widespread vaccines in the world. We compared the detection of anti-S1 SARS-CoV2 IgG and the profile of inflammatory and cytotoxic responses of patients who developed different clinical outcomes of COVID-19 with individuals previously exposed or not to the virus received the first and booster doses of ChAdOx1 nCoV-19. Plasma from 35 patients with COVID-19 and 11 vaccinated were evaluated by multiplex assay. Here, no vaccinated subjects had serious adverse effects. Those vaccinated with a booster dose had higher anti-S1 IgG than mild/moderate and recovered patients. Critically ill and deceased patients had IgG levels like those immunized. By univariate analysis, IL-2, IL-17, and perforin do not differentiate between patients and vaccinated individuals. Granzyme A increased at dose 1, while patients had their levels reduced. High levels of granulysin, sFas, and IL-6 were detected in the deaths, but after vaccination, all were declined. The multivariate analysis supports the role of IL-6 and granulysin as associated and non-confounding variables related to the worst clinical outcome of COVID-19, but not sFas. Our data confirm the ability of the ChAdOx1 vaccine to produce specific antibody levels up to booster time. Furthermore, our data suggest that the vaccine can regulate both the hyper-production and the kinetics of the production of inflammatory and cytotoxic mediators involved in the cytokine storm, such as granulysin and IL-6.

摘要

在自然感染中会诱导免疫和细胞毒性介质,它们对疫苗接种的有效性至关重要。接种疫苗可用于预防 SARS-CoV-2 的传播并降低 COVID-19 的发病率/死亡率。ChAdOx1 nCoV-19 是世界上应用最广泛的疫苗之一。我们比较了发生不同 COVID-19 临床结局的患者与先前接触或未接触过病毒的个体对 SARS-CoV2 刺突蛋白(S1) IgG 的检测,以及炎症和细胞毒性反应的特征,这些个体接受了 ChAdOx1 nCoV-19 的第一剂和加强剂。通过多重分析评估了 35 名 COVID-19 患者和 11 名接种疫苗者的血浆。在这里,没有接种疫苗的受试者出现严重的不良反应。接受加强剂量接种的个体的抗 S1 IgG 水平高于轻症/中度和康复患者。危重症和死亡患者的 IgG 水平与免疫者相似。通过单变量分析,IL-2、IL-17 和穿孔素不能区分患者和接种个体。颗粒酶 A 在第 1 剂时增加,而患者的水平降低。在死亡病例中检测到高水平的颗粒溶素、sFas 和 IL-6,但接种疫苗后,所有这些水平都下降了。多变量分析支持 IL-6 和颗粒溶素作为与 COVID-19 最差临床结局相关的关联和非混杂变量的作用,但 sFas 不是。我们的数据证实了 ChAdOx1 疫苗能够在加强剂时间内产生特异性抗体水平。此外,我们的数据表明,疫苗可以调节细胞因子风暴中涉及的炎症和细胞毒性介质(如颗粒溶素和 IL-6)的过度产生和产生动力学。

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