Rajagopala Seesandra V, Strickland Britton A, Pakala Suman B, Kimura Kyle S, Shilts Meghan H, Rosas-Salazar Christian, Brown Hunter M, Freeman Michael H, Wessinger Bronson C, Gupta Veerain, Phillips Elizabeth, Mallal Simon A, Turner Justin H, Das Suman R
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Pathology Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
bioRxiv. 2022 Aug 23:2022.08.23.504908. doi: 10.1101/2022.08.23.504908.
Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes.
Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.
关于有症状早期新冠病毒（SARS-CoV-2）病毒载量与上呼吸道黏膜基因表达及免疫反应之间的关系，人们了解甚少。为了研究有症状的SARS-CoV-2早期病毒载量与上呼吸道黏膜基因表达的关联，我们对68例有症状的轻至中度新冠肺炎成年患者鼻咽拭子样本中的宿主黏膜转录组进行了分析。我们使用定量逆转录聚合酶链反应（qRT-PCR）测量SARS-CoV-2病毒载量。然后，我们研究了SARS-CoV-2病毒载量与上呼吸道黏膜免疫反应的关联。我们在所有样本中均检测到了SARS-CoV-2，并且从85%的有症状新冠肺炎成年患者样本中获得了>80%的基因组。呼吸道病毒组以SARS-CoV-2为主，共检测到的常见呼吸道病毒有限，即仅在6%的样本中鉴定出人类鼻病毒（HRV）。在对年龄、性别和种族进行校正后，我们观察到在有症状的轻至中度新冠肺炎成年患者中，SARS-CoV-2病毒载量与干扰素信号传导（OAS2、OAS3、IFIT1、UPS18、ISG15、ISG20、IFITM1和OASL）、趋化因子信号传导（CXCL10和CXCL11）以及适应性免疫系统（IFITM1、CD300E和SIGLEC1）基因之间存在显著正相关。有趣的是，这些基因中的大多数在CT值约为25时表达水平趋于平稳。总体而言，我们的数据表明，鼻腔黏膜对SARS-CoV-2感染的早期免疫反应依赖于病毒载量，这可能会改变新冠肺炎的预后。
此前的多项研究表明，SARS-CoV-2病毒载量可以预测疾病传播和严重程度的可能性。可检测到的较高SARS-CoV-2血浆病毒载量与更严重的呼吸道疾病相关。然而，SARS-CoV-2病毒载量与气道黏膜基因表达及免疫反应之间的关系仍不清楚。我们使用综合宏转录组学方法，对2020年春季感染SARS-CoV-2且有轻至中度症状的成年患者的鼻腔样本中的鼻黏膜转录组进行了分析。我们观察到新冠肺炎成年患者中，SARS-CoV-2病毒载量与干扰素信号传导、趋化因子信号传导以及适应性免疫系统之间存在正相关。我们的数据表明，鼻腔黏膜对SARS-CoV-2感染的早期免疫反应依赖于病毒载量，可能会改变新冠肺炎的预后。
