Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth

Florian Wimmers; Allison R Burrell; Yupeng Feng; Hong Zheng; Prabhu S Arunachalam; Mengyun Hu; Sara Spranger; Lindsay E Nyhoff; Devyani Joshi; Meera Trisal; Mayanka Awasthi; Lorenza Bellusci; Usama Ashraf; Sangeeta Kowli; Katherine C Konvinse; Emily Yang; Michael Blanco; Kathryn Pellegrini; Gregory Tharp; Thomas Hagan; R Sharon Chinthrajah; Tran T Nguyen; Alba Grifoni; Alessandro Sette; Kari C Nadeau; David B Haslam; Steven E Bosinger; Jens Wrammert; Holden T Maecker; Paul J Utz; Taia T Wang; Surender Khurana; Purvesh Khatri; Mary A Staat; Bali Pulendran

doi:10.1016/j.cell.2023.08.044

Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth

Cell. 2023 Oct 12;186(21):4632-4651.e23. doi: 10.1016/j.cell.2023.08.044. Epub 2023 Sep 29.

Authors

Florian Wimmers¹, Allison R Burrell², Yupeng Feng³, Hong Zheng⁴, Prabhu S Arunachalam³, Mengyun Hu³, Sara Spranger⁵, Lindsay E Nyhoff⁶, Devyani Joshi⁶, Meera Trisal³, Mayanka Awasthi⁷, Lorenza Bellusci⁷, Usama Ashraf⁸, Sangeeta Kowli⁹, Katherine C Konvinse¹⁰, Emily Yang¹¹, Michael Blanco¹², Kathryn Pellegrini¹³, Gregory Tharp¹³, Thomas Hagan¹⁴, R Sharon Chinthrajah¹⁵, Tran T Nguyen⁹, Alba Grifoni¹⁶, Alessandro Sette¹⁷, Kari C Nadeau¹⁵, David B Haslam¹⁴, Steven E Bosinger¹⁸, Jens Wrammert⁶, Holden T Maecker⁹, Paul J Utz¹¹, Taia T Wang¹⁹, Surender Khurana⁷, Purvesh Khatri⁴, Mary A Staat¹⁴, Bali Pulendran²⁰

Affiliations

¹ Department of Molecular Medicine, Interfaculty Institute for Biochemistry, University of Tuebingen, 72076 Tuebingen, Baden-Wuerttemberg, Germany; DFG Cluster of Excellence 2180 "Image-guided and Functional Instructed Tumor Therapy" (iFIT), University of Tuebingen, 72076 Tuebingen, Baden-Wuerttemberg, Germany; German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Baden-Wuerttemberg, Germany.
² Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Environmental and Public Health Sciences, Division of Epidemiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
³ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA.
⁴ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
⁵ Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁶ Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁷ Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
⁸ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA.
⁹ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
¹⁰ Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
¹¹ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹² Stanford Genomics Service Center, Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹³ Yerkes National Primate Research Center, Atlanta, GA 30024, USA.
¹⁴ Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
¹⁵ Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA 94305, USA.
¹⁶ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
¹⁷ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA 92037, USA.
¹⁸ Yerkes National Primate Research Center, Atlanta, GA 30024, USA; Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
¹⁹ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
²⁰ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: bpulend@stanford.edu.

PMID: 37776858
PMCID: PMC10724861 (available on 2024-10-12)
DOI: 10.1016/j.cell.2023.08.044

Abstract

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell multi-omics. Together, these data provide a snapshot of immunity to infection during the initial weeks and months of life.

Keywords: SARS-CoV-2; durability; infants; mucosal immunity; multi-omics; neonates; single-cell ATAC-seq; single-cell RNA-seq; viral infection.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19*
Child
Child, Preschool
Cytokines / metabolism
Humans
Immunity, Mucosal
Infant
Interferon-alpha
Multiomics
SARS-CoV-2* / metabolism

Substances

Cytokines
Interferon-alpha

Abstract

Publication types

MeSH terms

Substances

Grants and funding