Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19
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 o...
Saved in:
| Published in: | The Journal of experimental medicine Vol. 218; no. 8 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
02.08.2021
|
| Subjects: | |
| ISSN: | 1540-9538, 1540-9538 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | 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. |
|---|---|
| AbstractList | 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.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. 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. |
| Author | Ashley, Euan A Greenleaf, William J Wilk, Aaron J Martínez-Colón, Giovanny J Holmes, Susan Rabinovitch, Marlene Jimenez-Morales, David O'Hara, Ruth Blomkalns, Andra L Taylor, Shalina Wei, Bei Becker, Winston Parks, Benjamin Pi, Ruoxi Rogers, Angela J Blish, Catherine A Lee, Madeline J Nadeau, Kari C Ranganath, Thanmayi Yang, Samuel Zhao, Nancy Q |
| Author_xml | – sequence: 1 givenname: Aaron J orcidid: 0000-0003-1430-5852 surname: Wilk fullname: Wilk, Aaron J organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 2 givenname: Madeline J orcidid: 0000-0001-5039-6806 surname: Lee fullname: Lee, Madeline J organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 3 givenname: Bei orcidid: 0000-0003-1516-8802 surname: Wei fullname: Wei, Bei organization: Department of Genetics, Stanford University School of Medicine, Stanford, CA – sequence: 4 givenname: Benjamin orcidid: 0000-0002-0261-7472 surname: Parks fullname: Parks, Benjamin organization: Graduate Program in Computer Science, Stanford University School of Medicine, Stanford, CA – sequence: 5 givenname: Ruoxi orcidid: 0000-0002-2491-0979 surname: Pi fullname: Pi, Ruoxi organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 6 givenname: Giovanny J orcidid: 0000-0001-6792-8004 surname: Martínez-Colón fullname: Martínez-Colón, Giovanny J organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 7 givenname: Thanmayi orcidid: 0000-0001-9865-2119 surname: Ranganath fullname: Ranganath, Thanmayi organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 8 givenname: Nancy Q orcidid: 0000-0001-6217-854X surname: Zhao fullname: Zhao, Nancy Q organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 9 givenname: Shalina orcidid: 0000-0002-5573-6483 surname: Taylor fullname: Taylor, Shalina organization: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA – sequence: 10 givenname: Winston orcidid: 0000-0001-7876-5060 surname: Becker fullname: Becker, Winston organization: Department of Genetics, Stanford University School of Medicine, Stanford, CA – sequence: 11 givenname: David orcidid: 0000-0003-4356-6461 surname: Jimenez-Morales fullname: Jimenez-Morales, David organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 12 givenname: Andra L orcidid: 0000-0001-5760-6351 surname: Blomkalns fullname: Blomkalns, Andra L organization: Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 13 givenname: Ruth orcidid: 0000-0001-6583-4995 surname: O'Hara fullname: O'Hara, Ruth organization: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA – sequence: 14 givenname: Euan A orcidid: 0000-0001-9418-9577 surname: Ashley fullname: Ashley, Euan A organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 15 givenname: Kari C orcidid: 0000-0002-2146-2955 surname: Nadeau fullname: Nadeau, Kari C organization: Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA – sequence: 16 givenname: Samuel orcidid: 0000-0003-1123-9036 surname: Yang fullname: Yang, Samuel organization: Department of Emergency Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 17 givenname: Susan orcidid: 0000-0002-2208-8168 surname: Holmes fullname: Holmes, Susan organization: Department of Statistics, Stanford University, Stanford, CA – sequence: 18 givenname: Marlene orcidid: 0000-0001-7886-7104 surname: Rabinovitch fullname: Rabinovitch, Marlene organization: Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Stanford, CA – sequence: 19 givenname: Angela J orcidid: 0000-0001-6969-6200 surname: Rogers fullname: Rogers, Angela J organization: Department of Medicine, Stanford University School of Medicine, Stanford, CA – sequence: 20 givenname: William J orcidid: 0000-0003-1409-3095 surname: Greenleaf fullname: Greenleaf, William J organization: Department of Applied Physics, Stanford University, Stanford, CA – sequence: 21 givenname: Catherine A orcidid: 0000-0001-6946-7627 surname: Blish fullname: Blish, Catherine A organization: Chan Zuckerberg Biohub, San Francisco, CA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34128959$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkLtPwzAYxC1URB-wMSOPLCl-NvaIyqtSURdgjVz7S3EVOyFOQP3vCaJITHfS_XTS3RSNYh0BoUtK5pQocbOHMGeEUSIVO0ETKgXJtORq9M-P0TSlPSFUCLk4Q2MuKFNa6gkqn_uq81kdvMVNW5e-8nGHW_gEUyX85R2kpgXjsDukFnZ9ZTpfR1yX2MdoOsA-hD767oBNdPgdgunqpvaQfBoIvNy8re4yqs_RaTkUwsVRZ-j14f5l-ZStN4-r5e06s1yJLrMSnASucqnBaceFWRDrnOG6NErmuR7CrVK5FqCAgOXcGO0szwm3w1bCZuj6t3fY8tFD6orgk4WqMhHqPhVMCsoZX-Q_6NUR7bcBXNG0Ppj2UPx9w74BPY5omA |
| CitedBy_id | crossref_primary_10_1016_j_ccc_2022_02_001 crossref_primary_10_7554_eLife_77943 crossref_primary_10_1093_bib_bbad159 crossref_primary_10_1093_bfgp_elad003 crossref_primary_10_3390_life13030712 crossref_primary_10_3390_biomedicines10051002 crossref_primary_10_1038_s41598_022_26657_2 crossref_primary_10_3389_fmed_2022_915367 crossref_primary_10_3390_immuno5030035 crossref_primary_10_1002_eji_202250090 crossref_primary_10_1007_s00281_022_00972_2 crossref_primary_10_1021_acs_biomac_5c00168 crossref_primary_10_1111_cas_70171 crossref_primary_10_1128_jvi_00038_24 crossref_primary_10_1007_s00018_022_04220_6 crossref_primary_10_1126_science_abm8108 crossref_primary_10_1097_BS9_0000000000000132 crossref_primary_10_3390_cells13040300 crossref_primary_10_1080_02664763_2022_2064975 crossref_primary_10_3389_fimmu_2023_1329026 crossref_primary_10_1186_s13054_022_04002_3 crossref_primary_10_3389_fimmu_2023_1167639 crossref_primary_10_1038_s41590_023_01517_x crossref_primary_10_1038_s41593_024_01726_z crossref_primary_10_1038_s41598_024_56328_3 crossref_primary_10_1093_bib_bbae626 crossref_primary_10_1371_journal_ppat_1011898 crossref_primary_10_2147_JIR_S379331 crossref_primary_10_1126_scitranslmed_adn7527 crossref_primary_10_3390_vaccines10101762 crossref_primary_10_1186_s12916_021_02228_6 crossref_primary_10_3389_fimmu_2024_1273942 crossref_primary_10_1038_s41587_023_01782_z crossref_primary_10_1172_jci_insight_191314 crossref_primary_10_3390_v16010027 crossref_primary_10_1128_jvi_00647_25 crossref_primary_10_1002_jmv_28488 crossref_primary_10_1016_j_immuni_2025_05_020 crossref_primary_10_1016_j_clim_2022_108991 crossref_primary_10_1038_s41392_022_01237_y crossref_primary_10_1002_JLB_4A0322_164R crossref_primary_10_1186_s12964_024_01867_5 crossref_primary_10_3389_fimmu_2023_1194614 crossref_primary_10_1126_scitranslmed_adq1086 crossref_primary_10_1111_nyas_14739 crossref_primary_10_1002_jmv_28000 crossref_primary_10_1111_acel_13810 crossref_primary_10_1155_2022_9099136 crossref_primary_10_3390_app13042409 crossref_primary_10_1146_annurev_biodatasci_020422_050255 crossref_primary_10_1093_jbcr_irad178 crossref_primary_10_1002_jmv_70425 crossref_primary_10_1002_iid3_70137 crossref_primary_10_3390_ijms24054905 crossref_primary_10_1038_s41577_024_00998_7 crossref_primary_10_1016_j_jaci_2021_10_015 crossref_primary_10_1186_s12859_022_05126_7 crossref_primary_10_1038_s41598_023_49601_4 crossref_primary_10_1186_s12879_024_10139_z crossref_primary_10_1002_eji_202350465 crossref_primary_10_1016_j_patter_2025_101297 crossref_primary_10_1186_s12985_022_01923_x crossref_primary_10_1007_s00251_022_01284_3 crossref_primary_10_1038_s41698_025_01043_z crossref_primary_10_1038_s41590_025_02100_2 crossref_primary_10_1038_s43588_023_00476_5 crossref_primary_10_1126_scitranslmed_abm9151 crossref_primary_10_1128_CMR_00094_21 crossref_primary_10_1016_j_ebiom_2024_105343 crossref_primary_10_3389_fimmu_2022_879686 crossref_primary_10_3389_fimmu_2021_748097 crossref_primary_10_3390_ijms23052414 crossref_primary_10_4167_jbv_2024_54_4_284 crossref_primary_10_3390_ijms241310878 crossref_primary_10_1002_eji_202350633 crossref_primary_10_1038_s42003_025_08407_y crossref_primary_10_1681_ASN_2022010125 crossref_primary_10_3389_fped_2022_790273 crossref_primary_10_1111_imr_13109 crossref_primary_10_1016_j_xgen_2025_100889 crossref_primary_10_3390_ijms23169161 crossref_primary_10_1093_jleuko_qiad031 crossref_primary_10_1111_cpr_13496 crossref_primary_10_1186_s12859_022_05127_6 crossref_primary_10_1038_s41598_022_23533_x crossref_primary_10_1038_s41577_022_00744_x crossref_primary_10_1016_j_celrep_2024_114930 crossref_primary_10_1084_jem_20232192 crossref_primary_10_3390_ijms25073841 crossref_primary_10_4049_jimmunol_2300731 crossref_primary_10_1186_s13073_023_01208_0 crossref_primary_10_1016_j_dci_2022_104626 crossref_primary_10_1080_1750743X_2025_2460965 crossref_primary_10_1016_j_heliyon_2024_e31878 crossref_primary_10_1002_eji_202451145 crossref_primary_10_1016_j_jaip_2021_12_034 crossref_primary_10_1007_s13337_024_00859_w crossref_primary_10_1089_sur_2023_156 crossref_primary_10_1186_s42234_024_00163_4 crossref_primary_10_1007_s00253_022_12256_8 crossref_primary_10_1038_s41590_023_01560_8 crossref_primary_10_1186_s13073_024_01290_y crossref_primary_10_1016_j_intimp_2023_110055 crossref_primary_10_3390_v14020203 crossref_primary_10_3389_fimmu_2022_1010216 crossref_primary_10_1038_s41598_022_17368_9 crossref_primary_10_1093_cei_uxae045 crossref_primary_10_3390_microorganisms11082116 crossref_primary_10_1038_s41598_022_15668_8 crossref_primary_10_1016_j_pharmthera_2023_108508 crossref_primary_10_3389_fimmu_2022_842535 |
| ContentType | Journal Article |
| Contributor | Kumar, Komal Do, Evan de la Parte, Lauren Zhang, Wenming Visweswaran, Anita Thi Tran, Kim Quyen Lee, Madeline J. Whittle Dantzler, Kathleen Quinn, James V. Lyu, Shu-Chen Simpson, Laura Ashley, Euan A. Vergara, Rosemary Blomkalns, Andra L. Brewer, Rachel Hollis, Taylor Ugur, Michele Pi, Ruoxi Roque, Jonasel Fernandes, Andrea Zudock, Elizabeth J. Ivison, Geoff Haider, Kazim Nadeau, Kari C. Mann, Rosen Din, Hena Chang, Iris Martinez-Colon, Giovanny J. Newberry, Jennifer A. Wilk, Aaron J. O’Hara, Ruth Manohar, Monali Tal, Michal Zhao, Nancy Q. Baird, Andrea Krempski, James Ty, Maureen Bogusch, Drina Nahass, Georgie Rustagi, Arjun Ranganath, Thanmayi Blish, Catherine A. Rogers, Angela J. Yang, Samuel Jee, Kathryn McKechnie, Julia L. Kathale, Nimish Schreiber, Donald |
| Contributor_xml | – sequence: 1 givenname: Thanmayi surname: Ranganath fullname: Ranganath, Thanmayi – sequence: 2 givenname: Nancy Q. surname: Zhao fullname: Zhao, Nancy Q. – sequence: 3 givenname: Aaron J. surname: Wilk fullname: Wilk, Aaron J. – sequence: 4 givenname: Rosemary surname: Vergara fullname: Vergara, Rosemary – sequence: 5 givenname: Julia L. surname: McKechnie fullname: McKechnie, Julia L. – sequence: 6 givenname: Lauren surname: de la Parte fullname: de la Parte, Lauren – sequence: 7 givenname: Kathleen surname: Whittle Dantzler fullname: Whittle Dantzler, Kathleen – sequence: 8 givenname: Maureen surname: Ty fullname: Ty, Maureen – sequence: 9 givenname: Nimish surname: Kathale fullname: Kathale, Nimish – sequence: 10 givenname: Giovanny J. surname: Martinez-Colon fullname: Martinez-Colon, Giovanny J. – sequence: 11 givenname: Arjun surname: Rustagi fullname: Rustagi, Arjun – sequence: 12 givenname: Geoff surname: Ivison fullname: Ivison, Geoff – sequence: 13 givenname: Ruoxi surname: Pi fullname: Pi, Ruoxi – sequence: 14 givenname: Madeline J. surname: Lee fullname: Lee, Madeline J. – sequence: 15 givenname: Rachel surname: Brewer fullname: Brewer, Rachel – sequence: 16 givenname: Taylor surname: Hollis fullname: Hollis, Taylor – sequence: 17 givenname: Andrea surname: Baird fullname: Baird, Andrea – sequence: 18 givenname: Michele surname: Ugur fullname: Ugur, Michele – sequence: 19 givenname: Michal surname: Tal fullname: Tal, Michal – sequence: 20 givenname: Drina surname: Bogusch fullname: Bogusch, Drina – sequence: 21 givenname: Georgie surname: Nahass fullname: Nahass, Georgie – sequence: 22 givenname: Kazim surname: Haider fullname: Haider, Kazim – sequence: 23 givenname: Kim Quyen surname: Thi Tran fullname: Thi Tran, Kim Quyen – sequence: 24 givenname: Laura surname: Simpson fullname: Simpson, Laura – sequence: 25 givenname: Hena surname: Din fullname: Din, Hena – sequence: 26 givenname: Jonasel surname: Roque fullname: Roque, Jonasel – sequence: 27 givenname: Rosen surname: Mann fullname: Mann, Rosen – sequence: 28 givenname: Iris surname: Chang fullname: Chang, Iris – sequence: 29 givenname: Evan surname: Do fullname: Do, Evan – sequence: 30 givenname: Andrea surname: Fernandes fullname: Fernandes, Andrea – sequence: 31 givenname: Shu-Chen surname: Lyu fullname: Lyu, Shu-Chen – sequence: 32 givenname: Wenming surname: Zhang fullname: Zhang, Wenming – sequence: 33 givenname: Monali surname: Manohar fullname: Manohar, Monali – sequence: 34 givenname: James surname: Krempski fullname: Krempski, James – sequence: 35 givenname: Anita surname: Visweswaran fullname: Visweswaran, Anita – sequence: 36 givenname: Elizabeth J. surname: Zudock fullname: Zudock, Elizabeth J. – sequence: 37 givenname: Kathryn surname: Jee fullname: Jee, Kathryn – sequence: 38 givenname: Komal surname: Kumar fullname: Kumar, Komal – sequence: 39 givenname: Jennifer A. surname: Newberry fullname: Newberry, Jennifer A. – sequence: 40 givenname: James V. surname: Quinn fullname: Quinn, James V. – sequence: 41 givenname: Donald surname: Schreiber fullname: Schreiber, Donald – sequence: 42 givenname: Euan A. surname: Ashley fullname: Ashley, Euan A. – sequence: 43 givenname: Catherine A. surname: Blish fullname: Blish, Catherine A. – sequence: 44 givenname: Andra L. surname: Blomkalns fullname: Blomkalns, Andra L. – sequence: 45 givenname: Kari C. surname: Nadeau fullname: Nadeau, Kari C. – sequence: 46 givenname: Ruth surname: O’Hara fullname: O’Hara, Ruth – sequence: 47 givenname: Angela J. surname: Rogers fullname: Rogers, Angela J. – sequence: 48 givenname: Samuel surname: Yang fullname: Yang, Samuel |
| Copyright | 2021 Wilk et al. |
| Copyright_xml | – notice: 2021 Wilk et al. |
| CorporateAuthor | Stanford COVID-19 Biobank |
| CorporateAuthor_xml | – name: Stanford COVID-19 Biobank |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1084/jem.20210582 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1540-9538 |
| ExternalDocumentID | 34128959 |
| Genre | Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHGRI NIH HHS grantid: UM1 HG009436 – fundername: NIAID NIH HHS grantid: U19 AI057266 – fundername: NHGRI NIH HHS grantid: P50 HG007735 – fundername: NIGMS NIH HHS grantid: T32 GM007365 – fundername: NIAID NIH HHS grantid: T32 AI007290 – fundername: NIGMS NIH HHS grantid: R25 GM086262 – fundername: NICHD NIH HHS grantid: R01 HD103571 – fundername: NHGRI NIH HHS grantid: RM1 HG007735 – fundername: NHLBI NIH HHS grantid: K23 HL125663 – fundername: NIDA NIH HHS grantid: DP1 DA046089 |
| GroupedDBID | --- -~X 18M 29K 2WC 36B 4.4 53G 5GY 5RE 5VS ABOCM ABZEH ACGFO ACNCT ACPRK ADBBV AENEX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BTFSW C45 CGR CS3 CUY CVF D-I DIK DU5 E3Z EBS ECM EIF EMB F5P F9R GX1 H13 HYE IH2 KQ8 L7B N9A NPM O5R O5S OK1 P2P P6G R.V RHI SJN TR2 TRP UHB W8F WOQ 7X8 |
| ID | FETCH-LOGICAL-c384t-c5ed5e38759ed9d34a60cdda39fa857795e3b88794e8e0ec33aa9dc3703c54002 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 151 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000701683800003&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1540-9538 |
| IngestDate | Thu Oct 02 09:57:28 EDT 2025 Thu Apr 03 07:03:17 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 8 |
| Language | English |
| License | 2021 Wilk et al. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c384t-c5ed5e38759ed9d34a60cdda39fa857795e3b88794e8e0ec33aa9dc3703c54002 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-7876-5060 0000-0001-6969-6200 0000-0003-1516-8802 0000-0001-5760-6351 0000-0003-1123-9036 0000-0002-2491-0979 0000-0003-1409-3095 0000-0001-6583-4995 0000-0001-6946-7627 0000-0002-2146-2955 0000-0003-1430-5852 0000-0002-5573-6483 0000-0001-7886-7104 0000-0001-6792-8004 0000-0002-0261-7472 0000-0001-6217-854X 0000-0001-9418-9577 0000-0001-5039-6806 0000-0001-9865-2119 0000-0003-4356-6461 0000-0002-2208-8168 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC8210586 |
| PMID | 34128959 |
| PQID | 2541323670 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2541323670 pubmed_primary_34128959 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-08-02 |
| PublicationDateYYYYMMDD | 2021-08-02 |
| PublicationDate_xml | – month: 08 year: 2021 text: 2021-08-02 day: 02 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | The Journal of experimental medicine |
| PublicationTitleAlternate | J Exp Med |
| PublicationYear | 2021 |
| SSID | ssj0014456 |
| Score | 2.671106 |
| Snippet | Our understanding of protective versus pathological immune responses to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is limited by... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| SubjectTerms | Adult Aged Case-Control Studies COVID-19 - blood COVID-19 - genetics COVID-19 - immunology COVID-19 - mortality Cytokines - genetics Epigenesis, Genetic Female Hematopoiesis Humans Immunity, Innate - physiology Killer Cells, Natural - pathology Killer Cells, Natural - virology Male Middle Aged Monocytes - pathology Monocytes - virology Neutrophils - pathology Neutrophils - virology NF-kappa B - metabolism Proteomics Severity of Illness Index Single-Cell Analysis |
| Title | Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19 |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/34128959 https://www.proquest.com/docview/2541323670 |
| Volume | 218 |
| WOSCitedRecordID | wos000701683800003&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV07T8MwELaAIsTC-1FeMhKrVbe2m3hCqFDB0NIBULfIsR0UhiSQAuq_5-y46oSExJIliRSdL3ffPT-ErjLF_C4fosFbEMC3kqQRVUQw3gd3p4UQxpNNRONxPJ3KSUi41aGtcmETvaE2pXY58g4EMhA4uXVj19U7caxRrroaKDRWUYsBlHFaHU2XVQTOPXtr1xX_JfzZofGdxrzzZt0YOsQ7wq3g-w1ceicz3P7v5-2grQAv8U2jD7toxRZ7aGMUCuj7KPMDt8SNIuOGrhtcF3ZrnEAN8XdubF0BjDTYzMF3vgZuL1xmOC8KgKU49_MkszlWhcF-4WtZlRBt5zU8gQePLw-3pCsP0PPw7mlwTwLVAtEs5jOihTXCMghepDXSMK76VBujmMxULKJIws0U7JHkNrbUasaUkkYzsBcapEt7h2itKAt7jHDkMkk0NgBNFNc9GVuT0rQvNKUqBfvYRpcLCSagyq4-oQpbftbJUoZtdNQcQ1I1OzcScLagR0Ke_OHtU7Tpjta36fXOUCsDCdpztK6_Znn9ceF1BK7jyegHpGHGLA |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Multi-omic+profiling+reveals+widespread+dysregulation+of+innate+immunity+and+hematopoiesis+in+COVID-19&rft.jtitle=The+Journal+of+experimental+medicine&rft.au=Wilk%2C+Aaron+J&rft.au=Lee%2C+Madeline+J&rft.au=Wei%2C+Bei&rft.au=Parks%2C+Benjamin&rft.date=2021-08-02&rft.eissn=1540-9538&rft.volume=218&rft.issue=8&rft_id=info:doi/10.1084%2Fjem.20210582&rft_id=info%3Apmid%2F34128959&rft_id=info%3Apmid%2F34128959&rft.externalDocID=34128959 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1540-9538&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1540-9538&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1540-9538&client=summon |