Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome.
Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome.
复制标题
DOI：
10.1038/s41598-021-02489-4
复制
发表时间：
2021-11-25
影响因子：
4.6
通讯作者：
Hasan Z
中科院分区：
文献类型：
--
作者：
Masood KI;Yameen M;Ashraf J;Shahid S;Mahmood SF;Nasir A;Nasir N;Jamil B;Ghanchi NK;Khanum I;Razzak SA;Kanji A;Hussain R;E Rottenberg M;Hasan Z
了解针对SARS-CoV-2感染的关键宿主保护机制有助于改进COVID-19的治疗方式。我们使用血液转录组方法研究与不同COVID-19严重程度相关的生物标志物，比较严重和轻度症状疾病与无症状COVID-19和未感染对照。与无症状病例相比，有症状病例的抗原呈递受到抑制，但炎症和病毒mRNA翻译相关途径上调。在严重的COVID-19中，中性粒细胞标志物CD177上调，而干扰素刺激基因（ISGs）下调。无症状COVID-19患者表现为isg和体液反应基因上调，ICAM3和TLR8下调。在整个COVID-19疾病谱系中，我们发现与轻度和重度COVID-19相比，无症状患者I型干扰素（IFN）应答显著上调（IFNAR2、IRF2BP1、IRF4、MAVS、SAMHD1、TRIM1）或下调（SOCS3、IRF2BP2、IRF2BPL），与疾病进展相关的isg数量增加失调。这些数据表明，isg可能有效控制对SARS-CoV-2的初步早期反应。因此，我们假设在COVID-19早期使用I型干扰素治疗可能通过限制宿主中的SARS-CoV-2来限制疾病进展。
Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.
登录
查看更多内容
影响因子：
12.3
作者：
Aschenbrenner AC;Mouktaroudi M;Krämer B;Oestreich M;Antonakos N;Nuesch-Germano M;Gkizeli K;Bonaguro L;Reusch N;Baßler K;Saridaki M;Knoll R;Pecht T;Kapellos TS;Doulou S;Kröger C;Herbert M;Holsten L;Horne A;Gemünd ID;Rovina N;Agrawal S;Dahm K;van Uelft M;Drews A;Lenkeit L;Bruse N;Gerretsen J;Gierlich J;Becker M;Händler K;Kraut M;Theis H;Mengiste S;De Domenico E;Schulte-Schrepping J;Seep L;Raabe J;Hoffmeister C;ToVinh M;Keitel V;Rieke G;Talevi V;Skowasch D;Aziz NA;Pickkers P;van de Veerdonk FL;Netea MG;Schultze JL;Kox M;Breteler MMB;Nattermann J;Koutsoukou A;Giamarellos-Bourboulis EJ;Ulas T;German COVID-19 Omics Initiative (DeCOI)
通讯作者：
German COVID-19 Omics Initiative (DeCOI)
影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
影响因子：
7.3
作者：
Bhaskar, Sonu;Sinha, Akansha;Kutty, Shelby
通讯作者：
Kutty, Shelby
影响因子：
32.4
作者：
Krämer B;Knoll R;Bonaguro L;ToVinh M;Raabe J;Astaburuaga-García R;Schulte-Schrepping J;Kaiser KM;Rieke GJ;Bischoff J;Monin MB;Hoffmeister C;Schlabe S;De Domenico E;Reusch N;Händler K;Reynolds G;Blüthgen N;Hack G;Finnemann C;Nischalke HD;Strassburg CP;Stephenson E;Su Y;Gardner L;Yuan D;Chen D;Goldman J;Rosenstiel P;Schmidt SV;Latz E;Hrusovsky K;Ball AJ;Johnson JM;Koenig PA;Schmidt FI;Haniffa M;Heath JR;Kümmerer BM;Keitel V;Jensen B;Stubbemann P;Kurth F;Sander LE;Sawitzki B;Deutsche COVID-19 OMICS Initiative (DeCOI);Aschenbrenner AC;Schultze JL;Nattermann J
通讯作者：
Nattermann J
影响因子：
16.8
作者：
King C;Sprent J
通讯作者：
Sprent J