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

• Published in: Nature communications 2025-01, Vol.16 (1), p.586-16, Article 586
• Main 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, 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.
• Format: Article
• Language: English
• Subjects: 13/21; 38/1; 38/39; 38/91; 631/250/254; 631/250/255/2514; 631/326/596/4130; 692/308/575; 82/80; Adult; Aged; Antibodies, Viral - blood; Antibodies, Viral - immunology; Blood levels; Chemokines; Chemokines - blood; Chemokines - metabolism; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; Female; Gene Expression Profiling; Genes; Host Microbial Interactions - immunology; Humanities and Social Sciences; Humans; Immune clearance; Immunity; Immunity, Innate; Immunoglobulin G; Infectious diseases; Innate immunity; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Microorganisms; Middle Aged; multidisciplinary; Organ Transplantation - adverse effects; Prospective Studies; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Transplant Recipients; Transplants & implants; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-025-55823-z

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. Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.