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Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations
Jennifer R. Habel, … , Louise C. Rowntree, Katherine Kedzierska
Jennifer R. Habel, … , Louise C. Rowntree, Katherine Kedzierska
Published April 10, 2023
Citation Information: JCI Insight. 2023;8(7):e167157. https://doi.org/10.1172/jci.insight.167157.
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Research Article Immunology Infectious disease

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

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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.

Authors

Jennifer R. Habel, Brendon Y. Chua, Lukasz Kedzierski, Kevin J. Selva, Timon Damelang, Ebene R. Haycroft, Thi H.O. 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 S.Y. 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 Y.C. 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

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Figure 3

Differential NK cell activation dynamics in pregnant women with COVID-19.

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Differential NK cell activation dynamics in pregnant women with COVID-19...
(A) CD3–CD56+ NK cell activation by HLA-DR expression. (B) HLA-DR+ NK cell frequencies in healthy (P, n = 18; Non-P, n = 13), acute (P, n = 17; Non-P, n = 17), and convalescent (P, n = 17; Non-P, n = 18) COVID-19 pregnant and nonpregnant women. (C) Fold difference in the mean frequency of HLA-DR+ NK cells between healthy and acute groups. (D) LOESS regression of HLA-DR+ NK cell frequencies and DPSO for pregnant and nonpregnant women with COVID-19. The 95% CI is shown in gray. (E) Proportions of CD56brightCD16–, CD56dimCD16+, and intermediate non–CD56bright/dim NK cells. (F) Frequencies of HLA-DR+ CD56brightCD16– (left) and CD56dimCD16+ (right) NK cells in healthy (P, n = 18; Non-P, n = 13), acute (P, n = 17; Non-P, n = 17), and convalescent (P, n = 17; Non-P, n = 18) pregnant and nonpregnant women. (G) Proportions of CD56brightCD16–, CD56dimCD16+, and intermediate non–CD56bright/dim in HLA-DR+ NK cells. (H and I) Proportions of granzyme and perforin expression in (H) CD56dimCD16+ or (I) CD56brightCD16– NK cells. Means and SDs are shown in B and E–G. Significance determined by Kruskal-Wallis test (B and E–G), Wald’s test (D), or permutations test (H and I). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Copyright © 2023 American Society for Clinical Investigation
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