Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients

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, 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 and Charles R. Langelier ()
Additional contact information
Harry Pickering: University of California Los Angeles
Joanna Schaenman: University of California Los Angeles
Hoang Van Phan: University of California San Francisco
Cole Maguire: The University of Texas at Austin
Alexandra Tsitsiklis: University of California San Francisco
Nadine Rouphael: Emory School of Medicine
Nelson Iván Agudelo Higuita: Oklahoma University Health Sciences Center
Mark A. Atkinson: University of Florida
Scott Brakenridge: University of Florida
Monica Fung: University of California San Francisco
William Messer: Oregon Health Sciences University
Ramin Salehi-rad: University of California Los Angeles
Matthew C. Altman: University of Washington
Patrice M. Becker: National Institute of Allergy and Infectious Diseases/National Institutes of Health
Steven E. Bosinger: Emory School of Medicine
Walter Eckalbar: University of California San Francisco
Annmarie Hoch: Boston Children’s Hospital
Naresh Doni Jayavelu: University of Washington
Seunghee Kim-Schulze: Icahn School of Medicine at Mount Sinai
Meagan Jenkins: University of California Los Angeles
Steven H. Kleinstein: Yale School of Medicine
Florian Krammer: Icahn School of Medicine at Mount Sinai
Holden T. Maecker: Stanford University School of Medicine
Al Ozonoff: Boston Children’s Hospital
Joann Diray-Arce: Boston Children’s Hospital
Albert Shaw: Yale School of Medicine
Lindsey Baden: Harvard Medical School
Ofer Levy: Boston Children’s Hospital
Elaine F. Reed: University of California Los Angeles
Charles R. Langelier: University of California San Francisco

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-55823-z

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