SARS-CoV-2 infection elucidates features of pregnancy-specific immunity

Dong Sun Oh; Eunha Kim; Rachelly Normand; Guangqing Lu; Lydia L Shook; Amanda Lyall; Olyvia Jasset; Stepan Demidkin; Emily Gilbert; Joon Kim; Babatunde Akinwunmi; Jessica Tantivit; Alice Tirard; Benjamin Y Arnold; Kamil Slowikowski; MGH COVID-19 Collection & Processing Team; Marcia B Goldberg; Michael R Filbin; Nir Hacohen; Long H Nguyen; Andrew T Chan; Xu G Yu; Jonathan Z Li; Lael Yonker; Alessio Fasano; Roy H Perlis; Ofer Pasternak; Kathryn J Gray; Gloria B Choi; David A Drew; Pritha Sen; Alexandra-Chloé Villani; Andrea G Edlow; Jun R Huh

doi:10.1016/j.celrep.2024.114933

SARS-CoV-2 infection elucidates features of pregnancy-specific immunity

Cell Rep. 2024 Nov 5;43(11):114933. doi: 10.1016/j.celrep.2024.114933. Online ahead of print.

Authors

Dong Sun Oh¹, Eunha Kim², Rachelly Normand³, Guangqing Lu¹, Lydia L Shook⁴, Amanda Lyall⁵, Olyvia Jasset⁶, Stepan Demidkin⁶, Emily Gilbert⁶, Joon Kim⁶, Babatunde Akinwunmi⁶, Jessica Tantivit⁷, Alice Tirard⁷, Benjamin Y Arnold⁷, Kamil Slowikowski³; MGH COVID-19 Collection & Processing Team; Marcia B Goldberg⁸, Michael R Filbin⁹, Nir Hacohen¹⁰, Long H Nguyen¹¹, Andrew T Chan¹², Xu G Yu¹³, Jonathan Z Li¹⁴, Lael Yonker¹⁵, Alessio Fasano¹⁶, Roy H Perlis¹⁷, Ofer Pasternak¹⁸, Kathryn J Gray¹⁹, Gloria B Choi²⁰, David A Drew¹⁷, Pritha Sen²¹, Alexandra-Chloé Villani²², Andrea G Edlow²³, Jun R Huh²⁴

Affiliations

¹ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
² Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; BK21 Graduate Program, Department of Biomedical Sciences and Department of Neuroscience, Korea University College of Medicine, Seoul 02841, Republic of Korea.
³ Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
⁴ Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁶ Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁷ Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
¹⁰ Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
¹¹ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹² Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Harvard Chan Microbiome in Public Health Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
¹³ Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
¹⁴ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹⁵ Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁶ Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁷ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
¹⁸ Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁹ Department of Obstetrics & Gynecology, University of Washington, Seattle, WA 98195, USA.
²⁰ The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
²¹ Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Transplant, Oncology, and Immunocompromised Host Group, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA.
²² Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02129, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
²³ Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: [email protected].
²⁴ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].

PMID: 39504241
DOI: 10.1016/j.celrep.2024.114933

Abstract

Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8⁺ T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection.

Keywords: COVID-19; CP: Immunology; SARS-CoV-2; T cells; cytokines; immune cells; immune responses; maternal immune activation; pregnancy; single-cell RNA-seq.