{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T21:35:51Z","timestamp":1763156151949,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>There is growing literature about the SARS-CoV-2 pathogenetic effects exerted during pregnancy and whether vertical transmission or premature birth is possible. It is not well known whether changes in the immune system of pregnant women may lead to a marked susceptibility to infectious processes and the risk of adverse maternal and neonatal complications such as preterm birth, spontaneous abortion, hospitalization in an intensive care unit, transmission to the fetus or newborns, and fetal mortality are poorly understood. Along with this ongoing debate, it is not well defined whether, during pregnancy, the role of host susceptibility in producing a specific inflammatory response to SARS-CoV-2 may represent distinctive markers of risk of vertical transmission. Furthermore, SARS-CoV-2 impact on the vaginal microbiome has not yet been described, despite mounting evidence on its possible effect on the gastrointestinal microbiome and its influence on infectious diseases and preterm labor. This report describes the impact of SARS-CoV-2 on a twin pregnancy diagnosed with infection at the third trimester of gestation including tissue infections, inflammatory response, antibody production, cytokine concentration, and vaginal microbiome composition. We identified a pattern of cytokines including IL1-Ra, IL-9 G-CSF, IL-12, and IL-8 differently expressed, already associated with previously infected patients. We detected a similar concentration of almost all the cytokines tested in both twins, suggesting that the SARS-CoV-2-induced cytokine storm is not substantially impaired during the placental passage. The analysis of the vaginal microbiome did not show relevant signs of dysbiosis, similar to other healthy pregnant women and twin healthy pregnancies. The aim of this report was to analyze the immunological response against SARS-CoV-2 infection and virus tissue tropism in a twin pregnancy.<\/jats:p>","DOI":"10.3390\/ijerph18063075","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T11:48:22Z","timestamp":1615981702000},"page":"3075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SARS-CoV-2 Infection and Inflammatory Response in a Twin Pregnancy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2092-3067","authenticated-orcid":false,"given":"Andrea","family":"Trombetta","sequence":"first","affiliation":[{"name":"Department of Medical, Surgical, and Health Sciences, University of Trieste, Piazzale Europa, 1, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manola","family":"Comar","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical, and Health Sciences, University of Trieste, Piazzale Europa, 1, 34127 Trieste, Italy"},{"name":"Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, via Dell\u2019istria 65\/1, 34124 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-7927","authenticated-orcid":false,"given":"Alberto","family":"Tommasini","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical, and Health Sciences, University of Trieste, Piazzale Europa, 1, 34127 Trieste, Italy"},{"name":"Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, via Dell\u2019istria 65\/1, 34124 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melania","family":"Canton","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical, and Health Sciences, University of Trieste, Piazzale Europa, 1, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-5537","authenticated-orcid":false,"given":"Giuseppina","family":"Campisciano","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, via Dell\u2019istria 65\/1, 34124 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nunzia","family":"Zanotta","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, via Dell\u2019istria 65\/1, 34124 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3456-4395","authenticated-orcid":false,"given":"Carolina","family":"Cason","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical, and Health Sciences, University of Trieste, Piazzale Europa, 1, 34127 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianpaolo","family":"Maso","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, via Dell\u2019istria 65\/1, 34124 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Maria","family":"Risso","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health \u201cIRCCS Burlo Garofolo\u201d, via Dell\u2019istria 65\/1, 34124 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/AOG.0000000000003979","article-title":"Clinical Findings and Disease Severity in Hospitalized Pregnant Women with Coronavirus Disease 2019 (COVID-19)","volume":"136","author":"Savasi","year":"2020","journal-title":"Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.21037\/tp.2020.02.06","article-title":"Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia","volume":"9","author":"Zhu","year":"2020","journal-title":"Transl. Pediatr."},{"key":"ref_4","first-page":"E009","article-title":"Analysis of the pregnancy outcomes in pregnant women with COVID-19 in Hubei Province","volume":"55","author":"Zhang","year":"2020","journal-title":"Zhonghua Fu Chan Ke Za Zhi"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1017\/S0950268817001972","article-title":"Epidemiology of seasonal influenza infection in pregnant women and its impact on birth outcomes","volume":"145","author":"Regan","year":"2017","journal-title":"Epidemiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cmi.2020.10.007","article-title":"Impact of COVID-19 on maternal and neonatal outcomes: A systematic review and meta-analysis","volume":"27","author":"Gjoka","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0140-6736(20)30360-3","article-title":"Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"ref_8","first-page":"1846","article-title":"Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn","volume":"323","author":"Dong","year":"2020","journal-title":"JAMA"},{"key":"ref_9","first-page":"1","article-title":"Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?","volume":"9","author":"Romero","year":"2020","journal-title":"eLife"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-18933-4","article-title":"Analysis of SARS-CoV-2 vertical transmission during pregnancy","volume":"11","author":"Fenizia","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/s41591-019-0450-2","article-title":"The vaginal microbiome and preterm birth","volume":"25","author":"Fettweis","year":"2019","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Segal, J.P., Mak, J.W.Y., Mullish, B.H., Alexander, J.L., Ng, S.C., and Marchesi, J.R. (2020). The gut microbiome: An under-recognised contributor to the COVID-19 pandemic?. Ther. Adv. Gastroenterol., 13.","DOI":"10.1177\/1756284820974914"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1159\/000358516","article-title":"Maternal plasma and amniotic fluid cytokines in monochorionic, diamniotic twin pregnancies complicated by twin-to-twin transfusion syndrome","volume":"35","author":"Fox","year":"2014","journal-title":"Fetal Diagn. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-20649-x","article-title":"In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis","volume":"8","author":"Campisciano","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jaci.2020.04.027","article-title":"Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19","volume":"146","author":"Yang","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Galv\u00e1n-Pe\u00f1a, S., Leon, J., Chowdhary, K., Michelson, D.A., Vijaykumar, B., Yang, L., Magnuson, A., Manickas-Hill, Z., Piechocka-Trocha, A., and Worrall, D.P. (2020). Profound Treg perturbations correlate with COVID-19 severity. bioRxiv.","DOI":"10.1101\/2020.12.11.416180"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e30916","DOI":"10.7554\/eLife.30916","article-title":"Computer-guided design of optimal microbial consortia for immune system modulation","volume":"7","author":"Stein","year":"2018","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/imr.12170","article-title":"Regulatory T-cell homeostasis: Steady-state maintenance and modulation during inflammation","volume":"259","author":"Smigiel","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Moosa, Y., Kwon, D., De Oliveira, T., and Wong, E.B. (2020). Determinants of Vaginal Microbiota Composition. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00467"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Flannery, D.D., Gouma, S., Dhudasia, M.B., Mukhopadhyay, S., Pfeifer, M.R., Woodford, E.C., Triebwasser, J.E., Gerber, J.S., Morris, J.S., and Weirick, M.E. (2021). Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios. JAMA Pediatr.","DOI":"10.1001\/jamapediatrics.2021.0038"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1002\/jmv.26589","article-title":"Evaluation of alpha defensin, IL-1 receptor antagonist, and IL-18 levels in COVID-19 patients with macrophage activation syndrome and acute respiratory distress syndrome","volume":"93","author":"Kerget","year":"2021","journal-title":"J. Med Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e20193","DOI":"10.2196\/20193","article-title":"Hazards of the cytokine storm and cytokine-targeted therapy in COVID-19 patients: A Review (Preprint)","volume":"22","author":"Quirch","year":"2020","journal-title":"J. Med. Internet Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e12989","DOI":"10.1111\/sji.12989","article-title":"T cell immunobiology and cytokine storm of COVID-19","volume":"93","author":"Luo","year":"2021","journal-title":"Scand. J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-020-03125-1","article-title":"Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome","volume":"11","author":"Sacchi","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/nsr\/nwaa041","article-title":"Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients","volume":"7","author":"Zhou","year":"2020","journal-title":"Natl. Sci. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"673","DOI":"10.2147\/JIR.S278335","article-title":"Inflammatory Cytokine: IL-17A Signaling Pathway in Patients Present with COVID-19 and Current Treatment Strategy","volume":"13","author":"Shibabaw","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/S0015-0282(00)00517-3","article-title":"Evidence of a TH 1 type response associated with recurrent miscarriage","volume":"73","author":"Jenkins","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e13195","DOI":"10.1111\/aji.13195","article-title":"IL-10 to TNF\u03b1 ratios throughout early first trimester can discriminate healthy pregnancies from pregnancy losses","volume":"83","author":"Kaislasuo","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.immuni.2018.07.017","article-title":"Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development","volume":"49","author":"Yockey","year":"2018","journal-title":"Immunity"},{"key":"ref_31","first-page":"2979","article-title":"Effects of intrahepatic cholestasis of pregnancy on hepatic function, changes of inflammatory cytokines and fetal outcomes","volume":"17","author":"Wang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Hu, L., Cui, Y., Qi, Z., Huang, X., Cai, L., Zhang, T., Yin, Y., Lu, Z., and Xiang, J. (2014). Roles of PPAR\u03b3\/NF-\u03baB Signaling Pathway in the Pathogenesis of Intrahepatic Cholestasis of Pregnancy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087343"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.cca.2020.06.017","article-title":"Cytokine storm induced by SARS-CoV-2","volume":"509","author":"Song","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"108576","DOI":"10.1016\/j.clim.2020.108576","article-title":"Interferon gamma, TGF-\u03b21 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients","volume":"220","author":"Villalba","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Cerbulo-Vazquez, A., Zavala-Barrios, B., Briones-Garduno, J.C., Guerrero-Avendano, G.M.L., Arriaga-Pizano, L., Ferat-Osorio, E., Cabrera-Rivera, G.L., Miranda-Cruz, P., de la Rosa, M.T.G., and Prieto-Chavez, J.L. (2020). Title Serological Cytokine and chemokine profile in pregnant women with COVID19 in Mexico City Running title Cytokine and chemokines in COVID19 pregnant patients. medRxiv.","DOI":"10.1101\/2020.07.14.20153585"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1093\/infdis\/jit296","article-title":"Plasmacytoid Dendritic Cells and CD8 T Cells from Pregnant Women Show Altered Phenotype and Function Following H1N1\/09 Infection","volume":"208","author":"Vanders","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1136\/gutjnl-2020-323020","article-title":"Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19","volume":"70","author":"Yeoh","year":"2021","journal-title":"Gut"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/6\/3075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:36:53Z","timestamp":1760161013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/6\/3075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijerph18063075"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18063075","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2021,3,17]]}}}