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

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

doi:10.1172/jci.insight.167157

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

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 AllenFatima 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e167157
Pages (from-to)	1-21
Number of pages	21
Journal	JCI Insight
Volume	8
Issue number	7
Early online date	22 Mar 2023
DOIs	https://doi.org/10.1172/jci.insight.167157
Publication status	Published - 10 Apr 2023

Keywords

Pregnancy
Female
Humans
COVID-19
SARS-CoV-2
Killer cells, Natural
CD8-positive T-lymphocytes
Antibodies

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Habel, J. R., Chua, B. Y., Kedzierski, L., Selva, K. J., Damelang, T., Haycroft, E. R., Nguyen, T. H., Koay, H.-F., Nicholson, S., McQuilten, H. A., Jia, X., Allen, L. F., Hensen, L., Zhang, W., van de Sandt, C. E., Neil, J. A., Pragastis, K., Lau, J. S., Jumarang, J., ... Kedzierska, K. (2023). Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations. JCI Insight, 8(7), 1-21. Article e167157. https://doi.org/10.1172/jci.insight.167157

@article{6edda58e6b244a2994667b1946da6243,

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

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 = "Pregnancy, Female, Humans, COVID-19, SARS-CoV-2, Killer cells, Natural, CD8-positive T-lymphocytes, Antibodies",

author = "Habel, {Jennifer R} and Chua, {Brendon Y} and Lukasz Kedzierski and Selva, {Kevin J} and Timon Damelang and Haycroft, {Ebene R} and Nguyen, {Thi Ho} and Hui-Fern Koay and Suellen Nicholson and McQuilten, {Hayley A} and Xiaoxiao Jia and Allen, {Lilith F} and Luca Hensen and Wuji Zhang and {van de Sandt}, {Carolien E} and Neil, {Jessica A} and Katherine Pragastis and Lau, {Jillian Sy} and Jaycee Jumarang and Allen, {E Kaitlynn} and Fatima Amanant and Florian Krammer and Wragg, {Kathleen M} and Juno, {Jennifer A} and Wheatley, {Adam K} and Hyon-Xhi Tan and Gabrielle Pell and Susan Walker and Jennifer Audsley and Arnold Reynaldi and Irani Thevarajan and Denholm, {Justin T} and Kanta Subbarao and Davenport, {Miles P} and Hogarth, {P Mark} and Godfrey, {Dale I} and Cheng, {Allen C} and Tong, {Steven YC} and Katherine Bond and Williamson, {Deborah A} and McMahon, {James H} and Thomas, {Paul G} and Pannaraj, {Pia S} and Fiona James and Holmes, {Natasha E} and Smibert, {Olivia C} and Trubiano, {Jason A} and Gordon, {Claire L} and Chung, {Amy W} and Whitehead, {Clare L} and Kent, {Stephen J} and Martha Lappas and Rowntree, {Louise C} and Katherine Kedzierska",

note = "Funding: This work was supported by the Australian NHMRC Leadership Investigator Grant (no. 1173871) to KK; Research Grants Council of Hong Kong Special Administrative Region, China (no. T11-712/19-N) to KK; Jack Ma Foundation to KK, KS, DIG, IT, and AWC; Victorian Government MRFF award (no. 2002073) to SJK, DIG, and AWC; MRFF Award (no. 1202445) to KK; MRFF Award (no. 2005544) to KK, SJK, DIG, AWC, ACC, DW, and JAJ; MRFF Award (no. 2016062) to KK, THON, LCR, SJK, JTD, AWC, ACC, MPD, and PGT; NHMRC Program Grant (no. 1149990) to SJK; NHMRC Program Grant (no. 1113293) to DIG; NIAID grant 1U01AI144616-01 to PGT, PSP, FK, and KK; and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to PGT and KK. THON was supported by an NHMRC Emerging Leadership Level-1 Investigator Grant (no. 1194036); HFK, CLG, and JAT by NHMRC Early Career Fellowships (nos. 1160333, 1160963, and 1139902); KS by NHMRC Investigator Grant (no. 1177174); DIG by NHMRC Senior Principal Research Fellowship (no. 1117766), and subsequently by an NHMRC Investigator Grant (no. 2008913); AWC by NHMRC Career Development Fellowship (no. 1140509); SJK by NHMRC Senior Principal Research Fellowship (no. 1136322); JRH and WZ by Melbourne Research Scholarships; LH by a Melbourne International Research Scholarship (MIRS) and Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne. XJ was supported by a China Scholarship Council-University of Melbourne joint Scholarship. JAJ was supported by an NHMRC Early Career Fellowship (no. 1123673). KK and AWC were supported by University of Melbourne Dame Kate Campbell Fellowships.",

year = "2023",

month = apr,

day = "10",

doi = "10.1172/jci.insight.167157",

language = "English",

volume = "8",

pages = "1--21",

journal = "JCI Insight",

issn = "2379-3708",

publisher = "The American Society for Clinical Investigation",

number = "7",

}

Habel, JR, Chua, BY, Kedzierski, L, Selva, KJ, Damelang, T, Haycroft, ER, Nguyen, TH, Koay, H-F, 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, H-X, Pell, G, Walker, S, Audsley, J, Reynaldi, A, Thevarajan, I, Denholm, JT, Subbarao, K, Davenport, MP, Hogarth, PM, Godfrey, DI, Cheng, AC, Tong, SYC, 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 2023, 'Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations', JCI Insight, vol. 8, no. 7, e167157, pp. 1-21. https://doi.org/10.1172/jci.insight.167157

TY - JOUR

T1 - Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations

AU - Habel, Jennifer R

AU - Chua, Brendon Y

AU - Kedzierski, Lukasz

AU - Selva, Kevin J

AU - Damelang, Timon

AU - Haycroft, Ebene R

AU - Nguyen, Thi Ho

AU - Koay, Hui-Fern

AU - Nicholson, Suellen

AU - McQuilten, Hayley A

AU - Jia, Xiaoxiao

AU - Allen, Lilith F

AU - Hensen, Luca

AU - Zhang, Wuji

AU - van de Sandt, Carolien E

AU - Neil, Jessica A

AU - Pragastis, Katherine

AU - Lau, Jillian Sy

AU - Jumarang, Jaycee

AU - Allen, E Kaitlynn

AU - Amanant, Fatima

AU - Krammer, Florian

AU - Wragg, Kathleen M

AU - Juno, Jennifer A

AU - Wheatley, Adam K

AU - Tan, Hyon-Xhi

AU - Pell, Gabrielle

AU - Walker, Susan

AU - Audsley, Jennifer

AU - Reynaldi, Arnold

AU - Thevarajan, Irani

AU - Denholm, Justin T

AU - Subbarao, Kanta

AU - Davenport, Miles P

AU - Hogarth, P Mark

AU - Godfrey, Dale I

AU - Cheng, Allen C

AU - Tong, Steven YC

AU - Bond, Katherine

AU - Williamson, Deborah A

AU - McMahon, James H

AU - Thomas, Paul G

AU - Pannaraj, Pia S

AU - James, Fiona

AU - Holmes, Natasha E

AU - Smibert, Olivia C

AU - Trubiano, Jason A

AU - Gordon, Claire L

AU - Chung, Amy W

AU - Whitehead, Clare L

AU - Kent, Stephen J

AU - Lappas, Martha

AU - Rowntree, Louise C

AU - Kedzierska, Katherine

N1 - Funding: This work was supported by the Australian NHMRC Leadership Investigator Grant (no. 1173871) to KK; Research Grants Council of Hong Kong Special Administrative Region, China (no. T11-712/19-N) to KK; Jack Ma Foundation to KK, KS, DIG, IT, and AWC; Victorian Government MRFF award (no. 2002073) to SJK, DIG, and AWC; MRFF Award (no. 1202445) to KK; MRFF Award (no. 2005544) to KK, SJK, DIG, AWC, ACC, DW, and JAJ; MRFF Award (no. 2016062) to KK, THON, LCR, SJK, JTD, AWC, ACC, MPD, and PGT; NHMRC Program Grant (no. 1149990) to SJK; NHMRC Program Grant (no. 1113293) to DIG; NIAID grant 1U01AI144616-01 to PGT, PSP, FK, and KK; and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to PGT and KK. THON was supported by an NHMRC Emerging Leadership Level-1 Investigator Grant (no. 1194036); HFK, CLG, and JAT by NHMRC Early Career Fellowships (nos. 1160333, 1160963, and 1139902); KS by NHMRC Investigator Grant (no. 1177174); DIG by NHMRC Senior Principal Research Fellowship (no. 1117766), and subsequently by an NHMRC Investigator Grant (no. 2008913); AWC by NHMRC Career Development Fellowship (no. 1140509); SJK by NHMRC Senior Principal Research Fellowship (no. 1136322); JRH and WZ by Melbourne Research Scholarships; LH by a Melbourne International Research Scholarship (MIRS) and Melbourne International Fee Remission Scholarship (MIFRS) from the University of Melbourne. XJ was supported by a China Scholarship Council-University of Melbourne joint Scholarship. JAJ was supported by an NHMRC Early Career Fellowship (no. 1123673). KK and AWC were supported by University of Melbourne Dame Kate Campbell Fellowships.

PY - 2023/4/10

Y1 - 2023/4/10

N2 - 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.

AB - 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.

KW - Pregnancy

KW - Female

KW - Humans

KW - COVID-19

KW - SARS-CoV-2

KW - Killer cells, Natural

KW - CD8-positive T-lymphocytes

KW - Antibodies

U2 - 10.1172/jci.insight.167157

DO - 10.1172/jci.insight.167157

M3 - Article

C2 - 37036008

SN - 2379-3708

VL - 8

SP - 1

EP - 21

JO - JCI Insight

JF - JCI Insight

IS - 7

M1 - e167157

ER -

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

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Keywords

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