Sarma Aartik, Christenson Stephanie A, Mick Eran, DeVoe Catherine, Deiss Thomas, Pisco Angela Oliveira, Ghale Rajani, Jauregui Alejandra, Byrne Ashley, Moazed Farzad, Spottiswoode Natasha, Sinha Pratik, Zha Beth Shoshana, Neff Norma, Tan Michelle, Serpa Paula Hayakawa, Ansel K Mark, Wilson Jennifer G, Leligdowicz Aleksandra, Siegel Emily R, Sirota Marina, DeRisi Joseph L, Matthay Michael A, Hendrickson Carolyn M, Kangelaris Kirsten N, Krummel Matthew F, Woodruff Prescott G, Erle David J, Calfee Carolyn S, Langelier Charles R
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, CA, USA.
Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Res Sq. 2021 Jan 14:rs.3.rs-141578. doi: 10.21203/rs.3.rs-141578/v1.
We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 was characterized by impaired interferon-stimulated gene expression (ISG). We found that the relationship between SARS-CoV-2 viral load and expression of ISGs was decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients with COVID-19 ARDS did not demonstrate cytokine storm but instead revealed a unique and dysregulated host response predicted to be modified by dexamethasone.
我们对52例因新型冠状病毒肺炎（COVID-19）或其他病因导致急性呼吸窘迫综合征（ARDS）的危重症患者以及无ARDS的对照者进行了下呼吸道转录谱比较分析。与细胞因子风暴相反，我们观察到与其他原因导致的ARDS相比，COVID-19相关ARDS中促炎基因表达降低。COVID-19相关ARDS的特征是宿主反应失调，PTEN信号增强，以及在炎症和免疫中具有非经典作用的基因表达升高，预计这些基因可被地塞米松和粒细胞集落刺激因子调节。与其他类型病毒性肺炎导致的ARDS相比，COVID-19的特征是干扰素刺激基因（ISG）表达受损。我们发现，与轻度COVID-19患者相比，COVID-19相关ARDS患者中严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒载量与ISG表达之间的关系脱节。总之，对COVID-19相关ARDS患者下呼吸道宿主基因表达的评估未显示细胞因子风暴，而是揭示了一种独特且失调的宿主反应，预计可被地塞米松改变。
