Abstract
Pregnant women are at higher risk of severe COVID-19, with vaccine access and hesitancy remaining a challenge. Here, we use a pregnant female hamster model of COVID-19 to explore the effects of maternal infection on pregnancy, revealing a significant increase in intrauterine growth restriction (IUGR) due to placental inflammation. Viral infection causes bronchopneumonia and weight loss in infected dams, but no vertical transmission occurs. IUGR is instead linked to placental damage, characterized by fibrin deposition, thrombosis, and elevated placental expression of IP10, IL6, and IL10, irrespective of fetal sex. Enoxaparin treatment reduces placental damage and improves fetal outcomes, while vaccination enhances viral clearance, protects the placenta, and reduces the risk of IUGR. These findings underscore placentitis as a key driver of fetal complications upon SARS-CoV-2 infection and highlight the potential of vaccination and anticoagulant therapy to protect both mother and child.
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Datasets generated and/or analyzed during the current study are provided in the paper or are appended as supplementary data. Source data are provided with this paper.
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Code for the analysis of sex distribution and confounding effect is available at https://github.com/Molecular-Vaccinology-Vaccine-Discovery/Kumpanenko-et-al-Nat-Commun-2026.
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Acknowledgements
The authors are grateful to Femke Vanzeebroeck, Valentijn Vergote, and the staff of the animal facility at the Rega Institute (KU Leuven) for their excellent support in establishing the hamster pregnancy model; to Elisabeth Heylen for her advice in the execution of experiments under controlled biosafety level 3 conditions; Katrien Luyten for her assistance in preparing placental slides for histological analysis. The authors are grateful to Prof. Joris Vriens and Dr. Bert Malengier-Devlies for their advice and helpful discussions. This work was supported by the Flemish Research Foundation (FWO, grant G0H3120N to H.V.V. and K.D.; Excellence of Science grant 40007527 to J.N. and K.D.), the KU Leuven Global Seed Fund (GSF/25/074 to Y.A.A. and K.D.), KU Leuven Internal Funding (C14/24/152 to K.D.C.), the European Union MSCA4Ukraine fellowship (grant 101110724 to Y.K.), and the European Union Horizon Europe Program (grant agreement 101137459 to K.D.). Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union, HADEA, or the MSCA4Ukraine Consortium. Neither the European Union nor the granting authority, nor the MSCA4Ukraine Consortium as a whole, nor any individual member institutions of the MSCA4Ukraine Consortium can be held responsible for them. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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Conceptualization: Y.A.A., K.D., and H.V.V. Methodology: Y.K., E.M., and Y.A.A. Formal analysis: Y.K. and Y.A.A. Investigation: Y.K., E.M., J.D., K.D.C., B.W., and Y.A.A. Resources: J.N., K.D., and K.D.C. Data curation: Y.K. and Y.A.A. Writing—original draft preparation: Y.K., Y.A.A., and K.D. Writing—review and editing: all authors. Visualization: Y.K. and Y.A.A. Supervision: Y.A.A. and K.D. Project administration: Y.A.A. and K.D. Funding acquisition: Y.K., Y.A.A., H.V.V., and K.D. All authors have read and agreed to the published version of the manuscript.
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K.D. and J.N. are mentioned as inventors on a patent application describing the construction and use of YF17D-based COVID-19 vaccines (EP4110380A1). The patent does not restrict academic research use of the described vaccine constructs; nor does it impose any restrictions on the publication, sharing, or reuse of the data presented in this study. All other authors declare to have no competing interests.
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Kumpanenko, Y., Maas, E., Degryse, J. et al. COVID-19-related inflammation of the placenta impedes fetal development in pregnant hamsters. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69360-w
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DOI: https://doi.org/10.1038/s41467-026-69360-w


