{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T17:02:30Z","timestamp":1768496550253,"version":"3.49.0"},"posted":{"date-parts":[[2021,8,23]]},"group-title":"Immunology","reference-count":39,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,8,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Pregnant women are an at-risk group for severe COVID-19, though the majority experience mild\/asymptomatic disease. Although severe COVID-19 has been shown to be associated with immune activation at the maternal-fetal interface even in the absence of active viral replication, the immune response to asymptomatic\/mild COVID-19 remains unknown. Here, we assessed immunological adaptations in both blood and term decidua from 9 SARS-exposed pregnant women with asymptomatic\/mild disease and 15 pregnant SARS-naive women. In addition to selective loss of tissue-resident decidual macrophages, we report attenuation of antigen presentation and type I IFN signaling but upregulation of inflammatory cytokines and chemokines in blood monocyte derived decidual macrophages. On the other hand, infection was associated with remodeling of the T cell compartment with increased frequencies of activated CD69+ tissue-resident T cells and decreased abundance of Tregs. Interestingly, frequencies of cytotoxic CD4 and CD8 T cells increased only in the blood, while CD8 effector memory T cells were expanded in the decidua. In contrast to decidual macrophages, signatures of type I IFN signaling were increased in decidual T cells. Finally, T cell receptor diversity was significantly reduced with infection in both compartments, albeit to a much greater extent in the blood. The resulting aberrant immune activation in the placenta, even with asymptomatic disease may alter the exquisitely sensitive developing fetal immune system, leading to long-term adverse outcomes for offspring.<\/jats:p>","DOI":"10.1101\/2021.08.23.457408","type":"posted-content","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T03:55:15Z","timestamp":1629777315000},"source":"Crossref","is-referenced-by-count":2,"title":["Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4141-8564","authenticated-orcid":false,"given":"Suhas","family":"Sureshchandra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3203-7866","authenticated-orcid":false,"given":"Michael Z","family":"Zulu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna","family":"Doratt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen","family":"Jankeel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-9337","authenticated-orcid":false,"given":"Delia","family":"Tifrea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Rincon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole E.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3203-2405","authenticated-orcid":false,"given":"Ilhem","family":"Messaoudi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2021082600200993000_2021.08.23.457408v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"issue":"7849","key":"2021082600200993000_2021.08.23.457408v1.2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/d41586-021-00578-y","article-title":"Pregnancy and COVID: what the data say","volume":"591","year":"2021","journal-title":"Nature"},{"key":"2021082600200993000_2021.08.23.457408v1.3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-041868"},{"issue":"16","key":"2021082600200993000_2021.08.23.457408v1.4","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1093\/cid\/ciaa352","article-title":"Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019 (COVID-19) Pneumonia: A Case-Control Study","volume":"71","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2021082600200993000_2021.08.23.457408v1.5","doi-asserted-by":"crossref","unstructured":"Edlow AG , Li JZ , Collier AY , Atyeo C , James KE , Boatin AA , et al. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. Jama Netw Open. 2020;3(12).","DOI":"10.1001\/jamanetworkopen.2020.30455"},{"key":"2021082600200993000_2021.08.23.457408v1.6","doi-asserted-by":"crossref","unstructured":"Lokken EM , Walker CL , Delaney S , Kachikis A , Kretzer NM , Erickson A , et al. Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State. 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An immune clock of human pregnancy. Sci Immunol. 2017;2(15).","DOI":"10.1126\/sciimmunol.aan2946"},{"issue":"3","key":"2021082600200993000_2021.08.23.457408v1.12","doi-asserted-by":"crossref","first-page":"347 e1","DOI":"10.1016\/j.ajog.2017.12.208","article-title":"A proteomic clock of human pregnancy","volume":"218","year":"2018","journal-title":"Am J Obstet Gynecol"},{"issue":"1","key":"2021082600200993000_2021.08.23.457408v1.13","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1038\/s41467-021-24940-w","article-title":"Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection","volume":"12","year":"2021","journal-title":"Nature Communications"},{"key":"2021082600200993000_2021.08.23.457408v1.14","doi-asserted-by":"crossref","unstructured":"Hojyo S , Uchida M , Tanaka K , Hasebe R , Tanaka Y , Murakami M , et al. How COVID-19 induces cytokine storm with high mortality. 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Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection The INTERCOVID Multinational Cohort Study. Jama Pediatrics. 2021.","DOI":"10.1001\/jamapediatrics.2021.1050"},{"key":"2021082600200993000_2021.08.23.457408v1.20","doi-asserted-by":"crossref","unstructured":"Lu-Culligan A , Chavan AR , Vijayakumar P , Irshaid L , Courchaine EM , Milano KM , et al. SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface. medRxiv. 2021.","DOI":"10.1016\/j.medj.2021.04.016"},{"key":"2021082600200993000_2021.08.23.457408v1.21","doi-asserted-by":"crossref","unstructured":"Garcia-Flores V , Romero R , Xu Y , Theis K , Arenas-Hernandez M , Miller D , et al. Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2. 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