Prior BNT162b vaccination enhances interferon-JAK-STAT regulated antiviral programs in hospitalized 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 Mononuclear Cells. Four patients had received the first dose of BNT162b 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 revealed an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase had subsided by day 35. Expression of the genes encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins was increased in the vaccinated group. We also investigated the immune transcriptome in naïve individuals receiving their first dose of BNT162b and identified 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 BNT162b 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 COVID-19 patients infected by SARS-CoV-2 Beta varient (Beta) and SARS-CoV-2 naïve vaccinated individuals.

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多样化的免疫应答与临床表型。本研究通过对外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMCs）进行RNA测序（RNA sequencing, RNA-seq），探究既往疫苗接种对感染SARS-CoV-2 Beta变异株的住院COVID-19患者先天免疫应答的影响。

4例患者在出现COVID-19症状前约11天接种了首剂BNT162b疫苗，5例患者未接种疫苗，所有患者均接受了地塞米松治疗。免疫转录组的采样时间分别为首次出现症状后的7-13天、20-32天及42-60天。

RNA-seq结果显示，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，由JAK-STAT通路介导的免疫转录组应答显著增强，该增强效应在第35天时消退。接种组中，与疾病严重程度呈负相关的抗病毒蛋白寡腺苷酸合成酶1（oligoadenylate synthetase 1, OAS1）及其他关键抗病毒蛋白的编码基因表达水平均有所升高。

本研究还对接种首剂BNT162b疫苗的SARS-CoV-2未感染个体的免疫转录组进行了分析，并鉴定出与接种疫苗的COVID-19患者共有的基因特征。

本研究证实，RNA-seq可用于监测未感染个体及COVID-19患者接种BNT162b疫苗后引发的分子免疫应答，并为系统疫苗学（systems vaccinology）提供了一种基于生物标志物的研究方法。

整体实验设计：本研究通过RNA-seq，对感染SARS-CoV-2 Beta变异株的COVID-19患者以及接种首剂BNT162b疫苗的SARS-CoV-2未感染个体的外周血单个核细胞进行测序分析。