Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients
Authors: Pickering Harry , Schaenman Joanna , Phan Hoang Van , Maguire Cole , Tsitsiklis Alexandra , Rouphael Nadine , Higuita Nelson Iván Agudelo , Atkinson Mark A. , Brakenridge Scott , Fung Monica , Messer William ,   IMPACC Network, Reed Elaine F. , Rivera Adreanne M. , Pickering Harry , Sen Subha , Elashoff David , Ward Dawn C. , Brook Jenny , Ramires-Sanchez Estefania , Llamas Megan , Perdomo Claudia , Magyar Clara E. , Fulcher Jennifer , Erle David J. , Calfee Carolyn S. , Hendrickson Carolyn M. , Kangelaris Kirsten N. , Nguyen Viet , Lee Deanna , Chak Suzanna , Ghale Rajani , Gonzalez Ana , Jauregui Alejandra , Leroux Carolyn , Altamirano Luz Torres , Rashid Ahmad Sadeed , Willmore Andrew , Woodruff Prescott G. , Krummel Matthew F. , Carrillo Sidney , Ward Alyssa , Patel Ravi , Wilson Michael , Dandekar Ravi , Alvarenga Bonny , Rajan Jayant , Schroeder Andrew W. , Fragiadakis Gabriela K. , Mick Eran , Guerrero Yanedth Sanchez , Love Christina , Maliskova Lenka , Adkisson Michael , Leligdowicz Aleksandra , Beagle Alexander , Rao Arjun , Sigman Austin , Samad Bushra , Curiel Cindy , Shaw Cole , Tietje-Ulrich Gayelan , Milush Jeff , Singer Jonathan , Vasquez Joshua J. , Tang Kevin , Betancourt Legna , Santhosh Lekshmi , Pierce Logan , Paz Maria Tecero , Matthay Michael M. , Thakur Neeta , Rodriguez Nicklaus , Sutter Nicole , Jones Norman , Sinha Pratik , Prasad Priya , Lota Raphael , Rashid Sadeed , Asthana Saurabh , Bhide Sharvari , Lea Tasha , Abe-Jones Yumiko , Ehrlich Lauren I. R. , Melamed Esther , Maguire Cole , Wylie Dennis , Rousseau Justin F. , Hurley Kerin C. , Geltman Janelle N. , Siles Nadia , Rogers Jacob E. , Tipan Pablo Guaman , Boddapati Arun K. , Tharp Greg K. , Pellegrini Kathryn L. , Johnson Brandi , Panganiban Bernadine , Huerta Christopher , Anderson Evan J. , Samaha Hady , Sevransky Jonathan E. , Bristow Laurel , Beagle Elizabeth , Cowan David , Hamilton Sydney , Hodder Thomas , Bechnak Amer , Cheng Andrew , Mehta Aneesh , Ciric Caroline R. , Spainhour Christine , Carter Erin , Scherer Erin M. , Usher Jacob , Hellmeister Kieffer , Hussaini Laila , Hewitt Lauren , Mcnair Nina , Ribeiro Susan Pereira , Wimalasena Sonia , Metcalf Jordan P. , Agudelo Higuita Nelson I. , Sinko Lauren A. , Booth J. Leland , Drevets Douglas A. , Brown Brent R. , Brakenridge Scott C. , Ungaro Ricardo F. , Manning Brittany Roth , Moldawer Lyle , Messer William B. , Hough Catherine L. , Siegel Sarah A. R. , Sullivan Peter E. , Lu Zhengchun , Brunton Amanda E. , Strand Matthew , Lyski Zoe L. , Coulter Felicity J. , Micheletti Courtney , Jayavelu Naresh Doni , Presnell Scott , Kohr Bernard , Jancsyk Tomasz , Arnett Azlann , Augustine Alison D. , Holland Steven M. , Rosen Lindsey B. , Lee Serena , Vaysman Tatyana , Ozonoff Al , Chen Jing , Kho Alvin T. , Milliren Carly E. , Chang Ana C. , McEnaney Kerry , Syphurs Caitlin , Barton Brenda , Lentucci Claudia , Murphy Maimouna D. , Saluvan Mehmet , Shaheen Tanzia , Liu Shanshan , Albert Marisa , Hayati Arash Nemati , Bryant Robert , Abraham James , Cooney Mitchell , Karoly Meagan , Steen Hanno , van Zalm Patrick , Fatou Benoit , Smolen Kinga K. , Viode Arthur , van Haren Simon , Jha Meenakshi , Stevenson David , Thomas Sanya , Petrova Boryana , Kanarek Naama , Fernandez-Sesma Ana , Simon Viviana , Van Bakel Harm , Gonzalez-Reiche Ana Silvia , Qi Jingjing , Lee Brian , Carreño Juan Manuel , Singh Gagandeep , Raskin Ariel , Tcheou Johnstone , Khalil Zain , van de Guchte Adriana , Farrugia Keith , Khan Zenab , Kelly Geoffrey , Srivastava Komal , Eaker Lily Q. , Bermúdez-González Maria C. , Mulder Lubbertus C. F. , Beach Katherine F. , Saksena Miti , Altman Deena , Kojic Erna , Sominsky Levy A. , Azad Arman , Bielak Dominika , Kawabata Hisaaki , Yellin Temima , Fried Miriam , Sullivan Leeba , Morris Sara , Kleiner Giulio , Stadlbauer Daniel , Dutta Jayeeta , Xie Hui , Patel Manishkumar , Nie Kai , Monahan Brian , Hafler David A. , Montgomery Ruth R. , Shaw Albert C. , Gygi Jeremy P. , Duchen Dylan , Pawar Shrikant , Konstorum Anna , Chen Ernie , Cotsapas Chris , Wang Xiaomei , Dela Cruz Charles , Iwasaki Akiko , Mohanty Subhasis , Nelson Allison , Zhao Yujiao , Farhadian Shelli , Asashima Hiromitsu , Chaudhary Omkar , Coppi Andreas , Fournier John , Muenker M. Catherine , Raddassi Khadir , Rainone Michael , Ruff William , Salahuddin Syim , Shulz Wade L. , Vijayakumar Pavithra , Wang Haowei , Wunder Esio , Young H. Patrick , Ko Albert I. , Gabernet Gisela , Esserman Denise , Guan Leying , Brito Anderson , Rothman Jessica , Grubaugh Nathan D. , Wang Kexin , Xu Leqi , Maecker Holden , Pulendran Bali , Nadeau Kari C. , Rosenberg-Hasson Yael , Leipold Michael , Sigal Natalia , Rogers Angela , Fernandes Andrea , Manohar Monali , Do Evan , Chang Iris , Lee Alexandra S. , Blish Catherine , Din Henna Naz , Roque Jonasel , Geng Linda N. , Artandi Maja , Davis Mark M. , Ahuja Neera , Yang Samuel S. , Chinthrajah Sharon , Hagan Thomas , Holmes Tyson H. , Abe Koji , Baden Lindsey R. , Mendez Kevin , Lasky-Su Jessica , Tong Alexandra , Rooks Rebecca , Desjardins Michael , Sherman Amy C. , Walsh Stephen R. , Mitre Xhoi , Cauley Jessica , Li Xiaofang , Evans Bethany , Montesano Christina , Licona Jose Humberto , Krauss Jonathan , Issa Nicholas C. , Chang Jun Bai Park , Izaguirre Natalie , Corry David B. , Kheradmand Farrah , Song Li-Zhen , Nelson Ebony , Kraft Monica , Bime Chris , Mosier Jarrod , Erickson Heidi , Schunk Ron , Kimura Hiroki , Conway Michelle , Francisco Dave , Molzahn Allyson , Wilson Connie Cathleen , Hughes Trina , Sierra Bianca , Oberhaus Jordan , Guirgis Faheem W. , Borresen Brittney , Anderson Matthew L. , Peters Bjoern , Overton James A. , Vita Randi , Westendorf Kerstin , Tebbutt Scott J. , Shannon Casey P. , Sekaly Rafick-Pierre , Fourati Slim , McComsey Grace A. , Harris Paul , Sieg Scott , Yendewa George , Consolo Mary , Tribout Heather , Ribeiro Susan Pereira , Cairns Charles B. , Haddad Elias K. , Kutzler Michele A. , Bernui Mariana , Cusimano Gina , Connors Jennifer , Woloszczuk Kyra , Joyner David , Edwards Carolyn , Lee Edward , Lin Edward , Melnyk Nataliya , Powell Debra L. , Kim James N. , Goonewardene I. Michael , Simmons Brent , Smith Cecilia M. , Martens Mark , Croen Brett , Semenza Nicholas C. , Bell Mathew R. , Furukawa Sara , McLin Renee , Tegos George P. , Rogowski Brandon , Mege Nathan , Ulring Kristen , Schearer Pam , Sheidy Judie , Nagle Crystal , Overton James A. , Hutton Scott R. , Michelotti Greg , Wong Kari , Rahman Adeeb , Seyfert-Margolis Vicki , Salehi-rad Ramin , Altman Matthew C. , Becker Patrice M. , Bosinger Steven E. , Eckalbar Walter , Hoch Annmarie , Doni Jayavelu Naresh , Kim-Schulze Seunghee , Jenkins Meagan , Kleinstein Steven H. , Krammer Florian , Maecker Holden T. , Ozonoff Al , Diray-Arce Joann , Shaw Albert , Baden Lindsey , Levy Ofer , Reed Elaine F. , Langelier Charles R. 
Published: January 2025

AbstractCoronavirus 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.