ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1560391
This article is part of the Research TopicInnate and Adaptive Immunity of Normal and Adverse PregnancyView all articles
Single-cell RNA-sequencing highlights a curtailed NK cell function in post COVID-19 pregnant women
Provisionally accepted
Madhuri S Salker1
Haslinda Abd Aziz2Natalia Prodan1
Zhiqi Yang1Aditya Kumar Lankapalli3
Katrin Lazar1
M Nasir Shafiee2Ersoy Kocak1Harivignesh Ganesan1Surya Sekhar Pal1Omer Khalid1Norhana Mohd Kasim2Aida Kalok2Norashikin Abdul Fuad4Alfred Lennart Bissinger1
Tina Ganzenmueller1
Thomas Iftner1Karl Oliver Kagan1
Stephan Ossowski1
Nicolas Casadei1DECOI Consortium5
Sara Yvonne Brucker1
Olaf Riess1
Yogesh Singh1*- 1University Hospital and Faculty of Medicine, University of Tübingen, Tübingen, Germany
- 2Universiti Kebangsaan Malaysia Medical Center (UKMMC), Cheras, Malaysia
- 3University of Oxford, Oxford, England, United Kingdom
- 4Hospital Sungai Buloh, Sungai Buloh, Selangor Darul Ehsan, Malaysia
- 5University of Bonn, Bonn, North Rhine-Westphalia, Germany
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During gestation the immune system undergoes dramatic remodelling to protect the maternal-fetal dyad from infections whilst also preventing fetal rejection. We investigated how SARS-CoV-2 modifies the immune landscape during infection and in recovered pregnant (post-COVID-19) women. Using two independent geographical cohorts, we identified that NK cells had a sustained reduction during active infection and after recovery quantified using flow cytometry. Further, our single-cell RNA sequencing (scRNA-seq) data revealed that infection with SARS-CoV-2 rewired the gene expression profile of NK, monocytes, CD4 + , CD8 + effector T cells and antibody producing B cells in convalescent pregnant women. Several gene pathways associated with cytotoxic function, interferon signalling type I & II, and pro-and anti-inflammatory functions in NK and CD8 + cytotoxic T cells were attenuated in recovered pregnant patients compared with healthy pregnancies. We validated our scRNA-seq of NK cells from convalescent pregnant women and confirmed that NK cells had diminished levels of cytotoxic proteins; perforin, CD122 and granzyme B. Overall, our study uncovers that SARS-CoV-2 infection deranges the adaptive immune response in pregnant women even after recovery and may contribute to post-COVID19 sequalae of symptoms.
Keywords: Pregnancy, COVID-19, PBMCs, NK cells and cytotoxic cells, ScRNA-seq
Received: 14 Jan 2025; Accepted: 16 May 2025.
Copyright: © 2025 Salker, Abd Aziz, Prodan, Yang, Lankapalli, Lazar, Shafiee, Kocak, Ganesan, Pal, Khalid, Kasim, Kalok, Fuad, Lennart Bissinger, Ganzenmueller, Iftner, Kagan, Ossowski, Casadei, Consortium, Brucker, Riess and Singh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yogesh Singh, University Hospital and Faculty of Medicine, University of Tübingen, Tübingen, Germany
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