Academic Journal
Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
| العنوان: | Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19 |
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| المؤلفون: | Wilk, Aaron J., Lee, Madeline J., Wei, Bei, Parks, Benjamin, Pi, Ruoxi, Martínez-Colón, Giovanny J., Ranganath, Thanmayi, Zhao, Nancy Q., Taylor, Shalina, Becker, Winston, Vergara, Rosemary, McKechnie, Julia L., de la Parte, Lauren, Whittle Dantzler, Kathleen, Ty, Maureen, Kathale, Nimish, Martinez-Colon, Giovanny J., Rustagi, Arjun, Ivison, Geoff, Brewer, Rachel, Hollis, Taylor, Baird, Andrea, Ugur, Michele, Tal, Michal, Bogusch, Drina, Nahass, Georgie, Haider, Kazim, Thi Tran, Kim Quyen, Simpson, Laura, Din, Hena, Roque, Jonasel, Mann, Rosen, Chang, Iris, Do, Evan, Fernandes, Andrea, Lyu, Shu-Chen, Zhang, Wenming, Manohar, Monali, Krempski, James, Visweswaran, Anita, Zudock, Elizabeth J., Jee, Kathryn, Kumar, Komal, Newberry, Jennifer A., Quinn, James V. |
| المساهمون: | National Heart, Lung, and Blood Institute, Stanford Medical Scientist Training Program, Stanford Bio-X, Wallenberg Foundation, National Institute of Standards and Technology, National Institute on Drug Abuse, Bill and Melinda Gates Foundation, Burroughs Wellcome Fund, Chan-Zuckerberg Initiative, Rita Allen Foundation, National Institutes of Health, Defense Advanced Research Projects Agency, Emerson Collective |
| المصدر: | Journal of Experimental Medicine ; volume 218, issue 8 ; ISSN 0022-1007 1540-9538 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2021 |
| الوصف: | Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses revealed widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, including prominent hyperactivation signatures in neutrophils and NK cells. We also identified chromatin accessibility changes at NF-κB binding sites within cytokine gene loci as a potential mechanism for the striking lack of pro-inflammatory cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrated that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity–associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20210582 |
| DOI: | 10.1084/jem.20210582/1828286/jem_20210582.pdf |
| الاتاحة: | http://dx.doi.org/10.1084/jem.20210582 https://rupress.org/jem/article-pdf/doi/10.1084/jem.20210582/1828286/jem_20210582.pdf |
| Rights: | http://www.rupress.org/terms/ ; https://creativecommons.org/licenses/by-nc-sa/4.0/ |
| رقم الانضمام: | edsbas.628907FE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20210582 |
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