{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:16:58Z","timestamp":1793197018994,"version":"4.5.0"},"reference-count":71,"publisher":"National Academy of Sciences","issue":"12","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"HHMI","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,24]]},"abstract":"<jats:p>Maternal viral infection during pregnancy has been identified as a risk factor for psychiatric disorders and neurodevelopmental abnormalities in offspring. With cumulative SARS-CoV-2 infections now numbering in the hundreds of millions globally, there is a need to evaluate the effects of maternal SARS-CoV-2 infection on offspring brain development and behavior. We developed a mouse model of mild COVID-19 during pregnancy in which SARS-CoV-2 infection is restricted to the respiratory tract. Infected mothers did not show weight loss or changes in litter size, but did exhibit detectable local and systemic immune responses, including placental inflammation. Characterization of the offspring\u2019s cerebral cortex revealed transcriptomic changes in the fetus at E15 and on postnatal day 5 (P5), but no gross alterations in cytoarchitecture, synaptic density, or microglial abundance. We did not detect any significant changes in open-field or novel object recognition tests in P50 offspring born to SARS-CoV-2-infected dams. These findings suggest that mild maternal respiratory SARS-CoV-2 infection induces soluble factors that mediate placental inflammation and transient cerebral cortex alterations in offspring that resolve by later childhood.<\/jats:p>","DOI":"10.1073\/pnas.2518294123","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:40:47Z","timestamp":1773855647000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Mild SARS-CoV-2 maternal infection in mice induces transient offspring neurodevelopmental aberrance"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-3926","authenticated-orcid":false,"given":"Wesley","family":"Tung","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine","place":["New Haven,"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Cai","sequence":"additional","affiliation":[{"name":"Child Study Center, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyesun","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine","place":["New Haven,"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-7071","authenticated-orcid":false,"given":"Harvey J.","family":"Kliman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2055-5885","authenticated-orcid":false,"given":"Robert J.","family":"Homer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Herrerias","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikkita","family":"Salla","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna Rodriguez","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3924-426X","authenticated-orcid":false,"given":"Kartik","family":"Pattabiraman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale University School of Medicine","place":["New Haven"]},{"name":"Child Study Center, Yale University School of Medicine","place":["New Haven"]},{"name":"Wu Tsai Institute, Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7824-9856","authenticated-orcid":false,"given":"Akiko","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine","place":["New Haven,"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12196322"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-023-06098-z"},{"key":"e_1_3_4_3_2","article-title":"The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California","volume":"2","author":"Karasek D.","year":"2021","unstructured":"D. Karasek , The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California. Lancet Reg. Health 2, 100027 (2021).","journal-title":"Lancet Reg. Health"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.10.001"},{"key":"e_1_3_4_5_2","article-title":"Maternal and neonatal outcomes of COVID-19 in pregnancy: A single-centre observational study","volume":"13","author":"Singh V.","year":"2021","unstructured":"V. Singh, A. Choudhary, M. R. Datta, A. Ray, Maternal and neonatal outcomes of COVID-19 in pregnancy: A single-centre observational study. Cureus 13, e13184 (2021).","journal-title":"Cureus"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-022-05101-3"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.202604"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170687"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.06.015"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.179068"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0314"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00610-y"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.04.057"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78294-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.7"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104223"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abi7428"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01169-x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27745-z"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2021.04.016"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.7396"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.39792"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.15787"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2021.5563"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000006112"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86452-3"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00087.2021"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46010023"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201241"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202135"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0778-2"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2023.101429"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2020.100759"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.06.029"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1086\/500850"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.14.2569"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2018.1498845"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00432"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-04743-w"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.08.013"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-022-00373-y"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02070"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-191-8_5"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10101517"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1439181"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/aji.70034"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","unstructured":"I. Mysorekar ORF3a is a key driver of maternal SARS-CoV-2 infection-associated placental dysfunction. Res Sq [Preprint] (2025) https:\/\/doi.org\/10.21203\/rs.3.rs-6857689\/v1 (Accessed 10 October 2025).","DOI":"10.21203\/rs.3.rs-6857689\/v1"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2025.110532"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60100"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00086-6"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2100686118"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3915"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.92342.3"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.07.017"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.06.001"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2023113796"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2023.105390"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02648-9"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009195"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13308"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009037"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.125"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat6576"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.049"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03953-x"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3956(99)00039-4"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.11.006"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2017.10.009"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa213"},{"key":"e_1_3_4_70_2","unstructured":"W. Tung Mild SARS-CoV-2 maternal infection in mice induces transient offspring neurodevelopmental aberrance. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE317803. Deposited 27 January 2026."},{"key":"e_1_3_4_71_2","unstructured":"W. Tung COVID-Pregnancy. Github. https:\/\/github.com\/caihelen\/covid-pregnancy. Deposited 3 February 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2518294123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:41:03Z","timestamp":1773855663000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2518294123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":71,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,3,24]]}},"alternative-id":["10.1073\/pnas.2518294123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2518294123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"2025-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2518294123"}}