Integrated immune networks in SARS-CoV-2 infected pregnant women reveal differential NK cell and unconventional T cell activation

Habel, J.; Chua, B.; Kedzierski, L.; Selva, K.; Damelang, T.; Haycroft, E.; Nguyen, T. H. O.; Koay, H.-F.; Nicholson, S.; McQuilten, H.; Jia, X.; Allen, L.; Hensen, L.; Zhang, W.; van de Sandt, C.; Neil, J.; Amanat, F.; Krammer, F.; Wragg, K.; Juno, J. A.; Wheatley, A. K.; Tan, H.-X.; Pell, G.; Audsley, J.; Thevarajan, I.; Denholm, J.; Subbarao, K.; Godfrey, D.; Cheng, A.; Tong, S.; Bond, K.; Williamson, D.; James, F.; Holmes, N.; Smibert, O.; Trubiano, J. A.; Gordon, C.; Chung, A. A.; Whitehead, C.; Kent, S.; Lappas, M.; Rowntree, L.; Kedzierska, K.

Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK cells, {gamma}{delta} T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of {beta} CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1{beta}, IFN-{gamma}, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.