{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:44:37Z","timestamp":1790502277142,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006143","name":"Department of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006143","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IMPRINT IIC","award":["IMP\/2019\/000115\/HT"],"award-info":[{"award-number":["IMP\/2019\/000115\/HT"]}]},{"name":"DBT Wellcome India alliance clinical and public health intermediate","award":["IA\/CPHI\/18\/1\/503933"],"award-info":[{"award-number":["IA\/CPHI\/18\/1\/503933"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Coronavirus disease 2019 (COVID-19) is caused by infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which survives in the tissues during the clinical course of infection but there is limited evidence on placental infection and vertical transmission of SARS-CoV-2. The impact of COVID-19 in first trimester pregnancy remains poorly understood. Moreover, how long SARS-CoV-2 can survive in placenta is unknown. Herein, we report a case of a pregnant woman in the first trimester who tested positive for SARS-CoV-2 at 8\u2009weeks of gestation, although her clinical course was asymptomatic. At 13\u2009weeks of gestation, her throat swab tested negative for SARS-CoV-2 but viral RNA was detected in the placenta, and the Spike (S) proteins (S1 and S2) were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. Histologically, the villi were generally avascular with peri-villus fibrin deposition and in some areas the syncytiotrophoblast layer appeared lysed. The decidua also had fibrin deposition with extensive leukocyte infiltration suggestive of inflammation. The SARS-CoV-2 crossed the placental barrier, as the viral RNA was detected in the amniotic fluid and the S proteins were detected in the fetal membrane. Ultrasonography revealed extensively subcutaneous edema with pleural effusion suggestive of hydrops fetalis and the absence of cardiac activity indicated fetal demise. This is the first study to provide concrete evidence of persistent placental infection of SARS-CoV-2 and its congenital transmission is associated with hydrops fetalis and intrauterine fetal demise in early pregnancy.<\/jats:p>","DOI":"10.1093\/humrep\/deaa367","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T15:22:31Z","timestamp":1607959351000},"page":"899-906","source":"Crossref","is-referenced-by-count":77,"title":["Persistence of SARS-CoV-2 in the first trimester placenta leading to transplacental transmission and fetal demise from an asymptomatic mother"],"prefix":"10.1093","volume":"36","author":[{"given":"Prajakta","family":"Shende","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, ESI-PGIMSR and Model Hospital Andheri, E.S.I.S. Hospital Kandivali, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, ESI-PGIMSR and Model Hospital Andheri, E.S.I.S. Hospital Kandivali, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Gandhewar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, ESI-PGIMSR and Model Hospital Andheri, E.S.I.S. Hospital Kandivali, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawankumar","family":"Ukey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, ESI-PGIMSR and Model Hospital Andheri, E.S.I.S. Hospital Kandivali, Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshul","family":"Bhide","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vainav","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharad","family":"Bhagat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikrant","family":"Bhor","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology and Microbiology, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Mahale","sequence":"additional","affiliation":[{"name":"Director and Department of Structural Biology, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Gajbhiye","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Modi","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"key":"2021031813501833900_deaa367-B1","doi-asserted-by":"crossref","first-page":"m3320","DOI":"10.1136\/bmj.m3320","article-title":"Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis","volume":"370","author":"Allotey","year":"2020","journal-title":"BMJ"},{"key":"2021031813501833900_deaa367-B2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.3389\/fcell.2020.00783","article-title":"Single-cell RNA-seq identifies cell subsets in human placenta that highly expresses factors driving pathogenesis of SARS-CoV-2","volume":"8","author":"Ashary","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2021031813501833900_deaa367-B3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/1093526620925569","article-title":"Placental pathology in Covid-19 positive mothers: preliminary findings","volume":"23","author":"Baergen","year":"2020","journal-title":"Pediatr Dev Pathol"},{"key":"2021031813501833900_deaa367-B4","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1038\/s41374-020-0464-x","article-title":"Detection of SARS-CoV-2 in formalin-fixed paraffin-embedded tissue sections using commercially available reagents","volume":"100","author":"Best Rocha","year":"2020","journal-title":"Lab Invest"},{"key":"2021031813501833900_deaa367-B5","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0140-6736(20)31305-2","article-title":"Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series","volume":"396","author":"Bradley","year":"2020","journal-title":"Lancet"},{"key":"2021031813501833900_deaa367-B6","doi-asserted-by":"crossref","first-page":"eabc4776","DOI":"10.1126\/science.abc4776","article-title":"SARS-CoV-2 infection protects against rechallenge in rhesus macaques","volume":"369","author":"Chandrashekar","year":"2020","journal-title":"Science"},{"key":"2021031813501833900_deaa367-B7","article-title":"Expression of SARS-CoV-2 receptor ACE2 and the spike protein processing enzymes in developing human embryos","author":"Colaco"},{"key":"2021031813501833900_deaa367-B8","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/j.cmi.2020.05.027","article-title":"Excretion of SARS-CoV-2 in human breast milk","volume":"26","author":"Costa","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"2021031813501833900_deaa367-B9","author":"Gajbhiye","year":"2020"},{"key":"2021031813501833900_deaa367-B10","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1210\/en.2017-00032","article-title":"Decrease in expression of HOXA10 in the decidua after embryo implantation promotes trophoblast invasion","volume":"158","author":"Godbole","year":"2017","journal-title":"Endocrinology"},{"key":"2021031813501833900_deaa367-B11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/codi.15138","article-title":"Persistent viral shedding of SARS-CoV-2 in faeces\u2014a rapid review","volume":"22","author":"Gupta","year":"2020","journal-title":"Colorectal Dis"},{"key":"2021031813501833900_deaa367-B12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"2021031813501833900_deaa367-B13","doi-asserted-by":"crossref","first-page":"4947","DOI":"10.1172\/JCI139569","article-title":"SARS-CoV-2 infection of the placenta","volume":"130","author":"Hosier","year":"2020","journal-title":"J Clin Invest"},{"key":"2021031813501833900_deaa367-B14","article-title":"Modelling and docking of Indian SARS-CoV-2 spike protein 1 with ACE2: implications for co-morbidity and therapeutic intervention","author":"Jagtap","year":"2020"},{"key":"2021031813501833900_deaa367-B15","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.3390\/jcm9061789","article-title":"Nonimmune hydrops fetalis\u2014prenatal diagnosis, genetic investigation, outcomes and literature review","volume":"9","author":"Kosinski","year":"2020","journal-title":"J Clin Med"},{"key":"2021031813501833900_deaa367-B16","doi-asserted-by":"crossref","first-page":"e0230295","DOI":"10.1371\/journal.pone.0230295","article-title":"The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study","volume":"15","author":"Li","year":"2020","journal-title":"PLoS One"},{"key":"2021031813501833900_deaa367-B17","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.3201\/eid2606.200287","article-title":"Lack of vertical transmission of severe acute respiratory syndrome coronavirus 2, China","volume":"26","author":"Li","year":"2020","journal-title":"Emerg Infect Dis"},{"key":"2021031813501833900_deaa367-B18","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.cmi.2020.06.035","article-title":"Vertical transmission and materno-fetal outcomes in 13 patients with coronavirus disease 2019","volume":"26","author":"Masmejan","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"2021031813501833900_deaa367-B19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/molehr\/gag031","article-title":"Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads","volume":"9","author":"Modi","year":"2003","journal-title":"Mol Hum Reprod"},{"key":"2021031813501833900_deaa367-B20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ajog.2014.12.018","article-title":"Society for maternal-fetal medicine (SMFM) clinical guideline #7: nonimmune hydrops fetalis","volume":"212","author":"Norton","year":"2015","journal-title":"Am J Obstet Gynecol"},{"key":"2021031813501833900_deaa367-B21","doi-asserted-by":"crossref","first-page":"522047","DOI":"10.3389\/fimmu.2020.522047","article-title":"Viral-immune cell interactions at the maternal-fetal interface in human pregnancy","volume":"11","author":"Parker","year":"2020","journal-title":"Front Immunol"},{"key":"2021031813501833900_deaa367-B22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/ajcp\/aqaa089","article-title":"Placental pathology in COVID-19","volume":"154","author":"Shanes","year":"2020","journal-title":"Am J Clin Pathol"},{"key":"2021031813501833900_deaa367-B23","author":"Shende","year":"2020"},{"key":"2021031813501833900_deaa367-B24","doi-asserted-by":"crossref","first-page":"108175","DOI":"10.1016\/j.celrep.2020.108175","article-title":"A single-cell RNA expression map of human coronavirus entry factors","volume":"32","author":"Singh","year":"2020","journal-title":"Cell Rep"},{"key":"2021031813501833900_deaa367-B25","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.virol.2006.11.027","article-title":"The intracellular sites of early replication and budding of SARS-coronavirus","volume":"361","author":"Stertz","year":"2007","journal-title":"Virology"},{"key":"2021031813501833900_deaa367-B26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.placenta.2020.08.015","article-title":"Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads","volume":"100","author":"Taglauer","year":"2020","journal-title":"Placenta"},{"key":"2021031813501833900_deaa367-B27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41467-020-17436-6","article-title":"Transplacental transmission of SARS-CoV-2 infection","volume":"11","author":"Vivanti","year":"2020","journal-title":"Nat Commun"},{"key":"2021031813501833900_deaa367-B28","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejogrb.2020.09.030","article-title":"Universal screening identifies asymptomatic carriers of SARS-CoV-2 among pregnant women in India","author":"Waghmare","year":"2021;256:503\u2013505.","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2021031813501833900_deaa367-B29","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S2468-1253(20)30083-2","article-title":"Prolonged presence of SARS-CoV-2 viral RNA in faecal samples","volume":"5","author":"Wu","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2021031813501833900_deaa367-B30","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41422-020-0318-5","article-title":"Pathological evidence for residual SARS-CoV-2 in pulmonary tissues of a ready-for-discharge patient","volume":"30","author":"Yao","year":"2020","journal-title":"Cell Res"},{"key":"2021031813501833900_deaa367-B31","doi-asserted-by":"crossref","first-page":"110195","DOI":"10.1016\/j.biopha.2020.110195","article-title":"New understanding of the damage of SARS-CoV-2 infection outside the respiratory system","volume":"127","author":"Zhang","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"2021031813501833900_deaa367-B32","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fpubh.2020.00487","article-title":"An overview of the temporal shedding of SARS-CoV-2 RNA in clinical specimens","volume":"8","author":"Zhurakivska","year":"2020","journal-title":"Front Public Health"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humrep\/advance-article-pdf\/doi\/10.1093\/humrep\/deaa367\/35905108\/deaa367.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/36\/4\/899\/36638177\/deaa367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/36\/4\/899\/36638177\/deaa367.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T09:52:03Z","timestamp":1616061123000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/36\/4\/899\/6042696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,21]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,12,21]]},"published-print":{"date-parts":[[2021,3,18]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deaa367","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.18.20177121","asserted-by":"object"}]},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,4,1]]},"published":{"date-parts":[[2020,12,21]]}}}