{"title":"Type I Interferonopathy among Non-Elderly Female Patients with Post-Acute Sequelae of COVID-19.","authors":"Donghua Xu, Xuebin Qin","doi":"10.3390/v16091369","DOIUrl":null,"url":null,"abstract":"<p><p>The pathophysiological mechanisms of the post-acute sequelae of COVID-19 (PASC) remain unclear. Sex differences not only exist in the disease severity of acute SARS-CoV-2 infection but also in the risk of suffering from PASC. Women have a higher risk of suffering from PASC and a longer time to resolution than men. To explore the possible immune mechanisms of PASC among non-elderly females, we mined single-cell transcriptome data from peripheral blood samples of non-elderly female patients with PASC and acute SARS-CoV-2 infection, together with age- and gender-matched non-PASC and healthy controls available from the Gene Expression Omnibus database. By comparing the differences, we found that a CD14<sup>+</sup> monocyte subset characterized by higher expression of signal transducers and activators of transcription 2 (STAT2) (CD14<sup>+</sup>STAT2<sup>high</sup>) was notably increased in the PASC patients compared with the non-PASC individuals. The transcriptional factor (TF) activity analysis revealed that STAT2 and IRF9 were the key TFs determining the function of CD14<sup>+</sup>STAT2<sup>high</sup> monocytes. STAT2 and IRF9 are TFs exclusively involving type I and III interferon (IFN) signaling pathways, resulting in uncontrolled IFN-I signaling activation and type I interferonopathy. Furthermore, increased expression of common interferon-stimulated genes (ISGs) has also been identified in most monocyte subsets among the non-elderly female PASC patients, including IFI6, IFITM3, IFI44L, IFI44, EPSTI1, ISG15, and MX1. This study reveals a featured CD14<sup>+</sup>STAT2<sup>high</sup> monocyte associated with uncontrolled IFN-I signaling activation, which is indicative of a possible type I interferonopathy in the non-elderly female patients with PASC.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435747/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Viruses-Basel","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/v16091369","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VIROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The pathophysiological mechanisms of the post-acute sequelae of COVID-19 (PASC) remain unclear. Sex differences not only exist in the disease severity of acute SARS-CoV-2 infection but also in the risk of suffering from PASC. Women have a higher risk of suffering from PASC and a longer time to resolution than men. To explore the possible immune mechanisms of PASC among non-elderly females, we mined single-cell transcriptome data from peripheral blood samples of non-elderly female patients with PASC and acute SARS-CoV-2 infection, together with age- and gender-matched non-PASC and healthy controls available from the Gene Expression Omnibus database. By comparing the differences, we found that a CD14+ monocyte subset characterized by higher expression of signal transducers and activators of transcription 2 (STAT2) (CD14+STAT2high) was notably increased in the PASC patients compared with the non-PASC individuals. The transcriptional factor (TF) activity analysis revealed that STAT2 and IRF9 were the key TFs determining the function of CD14+STAT2high monocytes. STAT2 and IRF9 are TFs exclusively involving type I and III interferon (IFN) signaling pathways, resulting in uncontrolled IFN-I signaling activation and type I interferonopathy. Furthermore, increased expression of common interferon-stimulated genes (ISGs) has also been identified in most monocyte subsets among the non-elderly female PASC patients, including IFI6, IFITM3, IFI44L, IFI44, EPSTI1, ISG15, and MX1. This study reveals a featured CD14+STAT2high monocyte associated with uncontrolled IFN-I signaling activation, which is indicative of a possible type I interferonopathy in the non-elderly female patients with PASC.
期刊介绍:
Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.