Abstract Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4 + and CD8 + T cells and T follicular helper cells was similar in SARS-CoV-2–infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy. Keywords: Immunology, Infectious disease Keywords: Innate immunity, NK cells, T cells
SHOW FULL ABSTRACT Jennifer R Habel, Brendon Y Chua, Lukasz Kedzierski, Kevin J Selva, Timon Damelang, Ebene R Haycroft, Thi HO Nguyen, Hui-Fern Koay, Suellen Nicholson, Hayley A McQuilten, Xiaoxiao Jia, Lilith F Allen, Luca Hensen, Wuji Zhang, Carolien E van de Sandt, Jessica A Neil, Katherine Pragastis, Jillian SY Lau, Jaycee Jumarang, E Kaitlynn Allen, Fatima Amanant, Florian Krammer, Kathleen M Wragg, Jennifer A Juno, Adam K Wheatley, Hyon-Xhi Tan, Gabrielle Pell, Susan Walker, Jennifer Audsley, Arnold Reynaldi, Irani Thevarajan, Justin T Denholm, Kanta Subbarao, Miles P Davenport, P Mark Hogarth, Dale I Godfrey, Allen C Cheng, Steven YC Tong, Katherine Bond, Deborah A Williamson, James H McMahon, Paul G Thomas, Pia S Pannaraj, Fiona James, Natasha E Holmes, Olivia C Smibert, Jason A Trubiano, Claire L Gordon, Amy W Chung, Clare L Whitehead, Stephen J Kent, Martha Lappas, Louise C Rowntree, Katherine Kedzierska
1Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 2Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan. 3Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia. 4Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 5Department of Infectious Diseases, Alfred Health, Monash University, Melbourne, Victoria, Australia. 6Department of Infectious Diseases, Eastern Health, Box Hill, Victoria, Australia. 7Division of Infectious Diseases, Children’s Hospital Los Angeles, Los Angeles, California, USA. 8Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA. 9Department of Microbiology, and 10Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 11ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, Victoria, Australia. 12Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia. 13Department of Infectious Diseases, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 14Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia. 15Victorian Infectious Diseases Service, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 16WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 17Immune Therapies Laboratory, Burnet Institute, Melbourne, Victoria, Australia. 18Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia. 19Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia. 20School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. 21Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, and Monash Infectious Diseases, Monash Health, Melbourne, Victoria, Australia. 22Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. 23Department of Microbiology, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 24Departments of Pediatrics, Molecular Microbiology and Immunology, Keck School of Medicine, UCLA, Los Angeles, California, USA. 25Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia. 26Department of Critical Care, University of Melbourne, Parkville, Victoria, Australia. 27Data Analytics Research and Evaluation Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia. 28Centre for Antibiotic Allergy and Research, Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia. 29Department of Infectious Diseases, and 30National Centre for Infections in Cancer, Peter McCallum Cancer Centre, Melbourne, Victoria, Australia. 31Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia. 32Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia. 33Pregnancy Research Centre, Royal Women’s Hospital, Parkville, Victoria, Australia. 34Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, Monash University, Melbourne, Victoria, Australia. 35Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia. 