@article{81a9c05530354af385803e067a54cc96,
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 SARSCoV-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.",
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 H.O.} and Koay, {Hui Fern} 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 S.Y.} 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 Tan, {Hyon Xhi} 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 Y.C.} 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 Information: We thank participants involved in the study; Jeni Mitchell, Zelda Williams, Veronica Link, Beverly Cox, Robyn Esterbauer, Hannah Kelly, Jane Batten, and Helen Kent for support with the cohort; and Jill Gar-lick, Janine Roney, Anne Paterson, and research nurses at the Alfred Hospital. We thank Bruce Wines for providing reagents for systems serology analyses. We acknowledge all DRASTIC (the use of cytokines as a predictor of disease severity in critically ill COVID patients) investigators from Austin Health, and thank participants involved. We thank Effie Mouhtouris and Ana Copaescu for laboratory work and study coordination of DRASTIC, and George Drewett for patient recruitment. This research included samples and data from the Sentinel Travelers Research Preparedness Platform for Emerging Infectious Diseases (SETREP-ID). We acknowledge SETREP-ID investigators and sites, and thank all participants involved. The authors thank Barbara Scher for setting up ethics and governance for SETREP-ID and the Australian Partnership for Preparedness Research for Infectious Disease Emergencies (APPRISE) for ongoing funding of SETREP-ID, Ajantha Rhodes, Judy Chang, Ashanti Dantanarayana, and Rosalyn Cao who contributed to the SETREP-ID biobank. SETREP-ID is supported by funding through the Australian National Health and Medical Research Council Centre of Research Excellence (NHMRC-CRE), Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE AppID-1116530), Snow Medical Foundation, Jack Ma Foundation, and A2 Milk Company. We thank Leo Lee and Francesca Mordant for assistance with microneutralization assays. 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. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. The images in Figure 1A and graphical abstract were created with BioRender. Publisher Copyright: Copyright: {\textcopyright} 2023, Habel et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.",
year = "2023",
doi = "10.1172/jci.insight.167157",
language = "English",
volume = "8",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "7",
}