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However, the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1093\/procel\/pwae006","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T17:43:24Z","timestamp":1709660604000},"page":"460-473","source":"Crossref","is-referenced-by-count":17,"title":["Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7038-7840","authenticated-orcid":false,"given":"Chenxiang","family":"Xi","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5491-6810","authenticated-orcid":false,"given":"Zihui","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2722-5114","authenticated-orcid":false,"given":"Dandan","family":"Bai","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"},{"name":"Jiaxing Maternity and Child Health Care Hospital , Jiaxing 314050 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-736X","authenticated-orcid":false,"given":"Yalin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiying","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Han","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqu","family":"Su","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binya","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiqing","family":"Yin","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocui","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-3928","authenticated-orcid":false,"given":"Shaorong","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-9900","authenticated-orcid":false,"given":"Wenqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University , Shanghai 200092 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"2024052810012134400_CIT0001","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3389\/fimmu.2016.00383","article-title":"The immune system of HIV-exposed uninfected 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