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Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and gammadelta T cell perturbations

Habel JR, Chua BY, Kedzierski L, Selva KJ, Damelang T, Haycroft ER, Nguyen TH, Koay HF, Nicholson S, McQuilten HA, Jia X, Allen LF, Hensen L, Zhang W, van de Sandt CE, Neil JA, Pragastis K, Lau JS, Jumarang J, Allen EK, Amanant F, Krammer F, Wragg KM, Juno JA, Wheatley AK, Tan HX, Pell G, Walker S, Audsley J, Reynaldi A, Thevarajan I, Denholm JT, Subbarao K, Davenport MP, Hogarth PM, Godfrey DI, Cheng AC, Tong SY, Bond K, Williamson DA, McMahon JH, Thomas PG, Pannaraj PS, James F, Holmes NE, Smibert OC, Trubiano JA, Gordon CL, Chung AW, Whitehead CL, Kent SJ, Lappas M, Rowntree LC, Kedzierska K

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  • Journal JCI Insight

  • Published 10 Apr 2023

  • Volume 8

  • ISSUE 7

  • Pagination e167157

  • DOI 10.3390/ijerph20032320

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.