Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients
Abstract Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55823-z |
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| author | Harry Pickering Joanna Schaenman Hoang Van Phan Cole Maguire Alexandra Tsitsiklis Nadine Rouphael Nelson Iván Agudelo Higuita Mark A. Atkinson Scott Brakenridge Monica Fung William Messer IMPACC Network Ramin Salehi-rad Matthew C. Altman Patrice M. Becker Steven E. Bosinger Walter Eckalbar Annmarie Hoch Naresh Doni Jayavelu Seunghee Kim-Schulze Meagan Jenkins Steven H. Kleinstein Florian Krammer Holden T. Maecker Al Ozonoff Joann Diray-Arce Albert Shaw Lindsey Baden Ofer Levy Elaine F. Reed Charles R. Langelier |
| author_facet | Harry Pickering Joanna Schaenman Hoang Van Phan Cole Maguire Alexandra Tsitsiklis Nadine Rouphael Nelson Iván Agudelo Higuita Mark A. Atkinson Scott Brakenridge Monica Fung William Messer IMPACC Network Ramin Salehi-rad Matthew C. Altman Patrice M. Becker Steven E. Bosinger Walter Eckalbar Annmarie Hoch Naresh Doni Jayavelu Seunghee Kim-Schulze Meagan Jenkins Steven H. Kleinstein Florian Krammer Holden T. Maecker Al Ozonoff Joann Diray-Arce Albert Shaw Lindsey Baden Ofer Levy Elaine F. Reed Charles R. Langelier |
| author_sort | Harry Pickering |
| collection | DOAJ |
| description | Abstract Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels. In addition, transplant recipients exhibit decreased plasmablasts and transitional B cells, and increased senescent T cells. Blood and nasal transcriptional profiling demonstrate unexpected upregulation of innate immune signaling pathways and increased levels of several proinflammatory serum chemokines. Severe disease in transplant recipients, however, is characterized by a less robust induction of pro-inflammatory genes and chemokines. Together, our study reveals distinct immune features and altered viral dynamics in solid organ transplant recipients. |
| format | Article |
| id | doaj-art-20b3ccc91d1c4a4d8f174764fa4ecf22 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-20b3ccc91d1c4a4d8f174764fa4ecf222025-01-12T12:30:30ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-55823-zHost-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipientsHarry Pickering0Joanna Schaenman1Hoang Van Phan2Cole Maguire3Alexandra Tsitsiklis4Nadine Rouphael5Nelson Iván Agudelo Higuita6Mark A. Atkinson7Scott Brakenridge8Monica Fung9William Messer10IMPACC NetworkRamin Salehi-rad11Matthew C. Altman12Patrice M. Becker13Steven E. Bosinger14Walter Eckalbar15Annmarie Hoch16Naresh Doni Jayavelu17Seunghee Kim-Schulze18Meagan Jenkins19Steven H. Kleinstein20Florian Krammer21Holden T. Maecker22Al Ozonoff23Joann Diray-Arce24Albert Shaw25Lindsey Baden26Ofer Levy27Elaine F. Reed28Charles R. Langelier29David Geffen School of Medicine, University of California Los AngelesDavid Geffen School of Medicine, University of California Los AngelesUniversity of California San FranciscoThe University of Texas at AustinUniversity of California San FranciscoEmory School of MedicineOklahoma University Health Sciences CenterUniversity of FloridaUniversity of FloridaUniversity of California San FranciscoOregon Health Sciences UniversityDavid Geffen School of Medicine, University of California Los AngelesBenaroya Research Institute, University of WashingtonNational Institute of Allergy and Infectious Diseases/National Institutes of HealthEmory School of MedicineUniversity of California San FranciscoPrecision Vaccines Program, Boston Children’s HospitalBenaroya Research Institute, University of WashingtonIcahn School of Medicine at Mount SinaiDavid Geffen School of Medicine, University of California Los AngelesYale School of MedicineIcahn School of Medicine at Mount SinaiStanford University School of MedicinePrecision Vaccines Program, Boston Children’s HospitalPrecision Vaccines Program, Boston Children’s HospitalYale School of MedicineHarvard Medical SchoolPrecision Vaccines Program, Boston Children’s HospitalDavid Geffen School of Medicine, University of California Los AngelesUniversity of California San FranciscoAbstract Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels. In addition, transplant recipients exhibit decreased plasmablasts and transitional B cells, and increased senescent T cells. Blood and nasal transcriptional profiling demonstrate unexpected upregulation of innate immune signaling pathways and increased levels of several proinflammatory serum chemokines. Severe disease in transplant recipients, however, is characterized by a less robust induction of pro-inflammatory genes and chemokines. Together, our study reveals distinct immune features and altered viral dynamics in solid organ transplant recipients.https://doi.org/10.1038/s41467-025-55823-z |
| spellingShingle | Harry Pickering Joanna Schaenman Hoang Van Phan Cole Maguire Alexandra Tsitsiklis Nadine Rouphael Nelson Iván Agudelo Higuita Mark A. Atkinson Scott Brakenridge Monica Fung William Messer IMPACC Network Ramin Salehi-rad Matthew C. Altman Patrice M. Becker Steven E. Bosinger Walter Eckalbar Annmarie Hoch Naresh Doni Jayavelu Seunghee Kim-Schulze Meagan Jenkins Steven H. Kleinstein Florian Krammer Holden T. Maecker Al Ozonoff Joann Diray-Arce Albert Shaw Lindsey Baden Ofer Levy Elaine F. Reed Charles R. Langelier Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients Nature Communications |
| title | Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients |
| title_full | Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients |
| title_fullStr | Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients |
| title_full_unstemmed | Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients |
| title_short | Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients |
| title_sort | host microbe multiomic profiling identifies distinct covid 19 immune dysregulation in solid organ transplant recipients |
| url | https://doi.org/10.1038/s41467-025-55823-z |
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