BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant. BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant

SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of peripheral blood immune cells. Four patients had received the first dose of BNT162b2 about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. RNA-seq reveals an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase subsides by day 35. Expression of the gene encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins increases in the vaccinated group. We also investigate the immune transcriptome in naïve individuals receiving their first dose of BNT162b2 and identify a gene signature shared with the vaccinated COVID-19 patients. Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b2 vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology. Overall design: RNA-seq were performed with peripheral blood mononuclear cells (PBMCs) of 9 COVID-19 patients infected by varient B.1.351of SARS-CoV-2 virus.

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染可激活干扰素调控的信号通路，并在人类患者中引发广谱免疫应答与多样化临床表现。本研究通过对外周血免疫细胞开展RNA测序（RNA sequencing, RNA-seq），探究了既往接种疫苗对感染SARS-CoV-2贝塔变异株的住院COVID-19患者先天免疫应答的影响。其中4名患者在出现COVID-19症状前约11天接种了首剂BNT162b2疫苗，另有5名患者未接种疫苗；所有患者均接受了地塞米松治疗。本研究分别在首次出现症状后的第7-13天、20-32天及第42-60天采集样本，获取免疫转录组数据。RNA-seq分析显示，与未接种疫苗的患者相比，接种疫苗的患者在症状出现后第10天呈现出更为显著的JAK-STAT介导的免疫转录组应答，该增强效应于第35天左右逐渐消退。编码抗病毒蛋白寡腺苷酸合成酶1（oligoadenylate synthetase 1, OAS1）的基因表达水平与疾病严重程度呈负相关，接种组中该基因及其他关键抗病毒蛋白的编码基因表达均出现上调。本研究同时对接种首剂BNT162b2疫苗的未感染个体的免疫转录组进行分析，并鉴定出与接种疫苗的COVID-19患者共有的基因特征谱。本研究证实，RNA-seq可用于监测未感染个体与COVID-19患者接种BNT162b2疫苗后引发的分子免疫应答，同时为系统疫苗学提供了基于生物标志物的研究路径。总体设计：本研究对9名感染SARS-CoV-2 B.1.351变异株的COVID-19患者的外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）开展了RNA-seq测序。