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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 2

Analysis of SARS-CoV-2–specific antibodies in pregnant and nonpregnant women.

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Analysis of SARS-CoV-2–specific antibodies in pregnant and nonpregnant w...
(A) Log10-transformed RBD-specific or N-specific antibody titers in pregnant (P) and nonpregnant (Non-P) healthy (P, n = 10–16; Non-P, n = 21–31), acute COVID-19 (P, n = 13–15; Non-P, n = 19), and convalescent COVID-19 (P, n = 17; Non-P, n = 31–41) donors. Orange dashed lines indicate seroconversion cutoff calculated from the mean + 2 SD of the healthy pregnant and nonpregnant titers. (B) sVNT percentage inhibition in acute (P, n = 13; Non-P, n = 11) and convalescent (P, n = 15; Non-P, n = 28) pregnant or nonpregnant women. Seropositivity indicated by orange dashed line. (C) LOESS regression of RBD- and N-IgG kinetics for pregnant (red) and nonpregnant (blue) COVID-19 donors. The 95% CI is shown in gray in B and C. (D) Proportions of pregnant, nonpregnant, and cord blood donors who seroconverted with different combinations of RBD-specific or neutralizing antibodies. Seroconversion counted if a donor had a positive readout at any time point if longitudinal samples were collected. (E) Principal component plots showing pregnant (red, n = 13) and nonpregnant (blue, n = 11) donors with acute COVID-19 (left). Loading plot showing features separating pregnant and nonpregnant donors along the PC1 axis (right). (F) Principal component plots showing pregnant (red, n = 8) and nonpregnant (blue, n = 10) donors with convalescent COVID-19 (left). Loading plot showing features separating pregnant and nonpregnant donors along the PC1 axis (right). SARS2, SARS-CoV-2; SARS1, SARS-CoV-1; S, spike; S1, spike subunit 1 (head); S2, spike subunit 2 (stalk); N, nucleocapsid; RBD, receptor binding domain. Means and SDs are shown in A and B. Significance determined with a Kruskal-Wallis test (A and B [left]) or with Wald’s test (B [right] and C) *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

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