Isabel Meister (@isabelmeister.bsky.social)

SARS-CoV-2 infection during the first trimester leads to profound immune dysregulation at the maternal-fetal interface despite limited virus detection in placental tissues | Nature Communications The endemic nature of SARS-CoV-2 underscores the imperative to elucidate its effects on pregnancy, particularly the potential for vertical transmission and its influence on the early maternal–fetal interface. Here, we performed an extensive cohort study involving 761 pregnant women who voluntarily terminated their pregnancies during the first trimester. Analyses conducted using RT‒qPCR, fluorescence in situ hybridisation, and indirect immunofluorescence showed low detection levels of SARS-CoV-2 infection within villous and decidual tissues. Single-cell RNA sequencing analysis revealed an absence of cell populations demonstrating significant coexpression of ACE2 and TMPRSS2, potentially providing a mechanistic explanation for the rare incidence of viral infection within placental tissues. The maternal systemic inflammatory response was activated, and the levels of IL-31, IL-5, and GRO-α were significantly elevated during acute infection. Furthermore, increased IgG titres were negatively correlated with TNF-β concentrations, suggesting a protective immunomodulatory function of IgG antibodies. Conversely, both bulk and single-cell transcriptomic analyses revealed pronounced, cell type-specific antiviral and immune responses within the placental microenvironment. A pervasive interferon-stimulated gene signature was identified, accompanied by the emergence of M2-like macrophages with diminished antigen presentation capacity during convalescence. Importantly, maternal SARS-CoV-2 infection disrupted intercellular communication networks, notably impairing the activity of the WNT and TGF-β signalling pathways in trophoblasts, thereby altering their differentiation trajectories. In summary, within this large cohort of first-trimester samples, we identified infrequent instances of SARS-CoV-2 infection in both villous and decidual tissues. Nonetheless, infection substantially perturbed the placental immune milieu and trophoblast dynamics, which may adversely affect pregnancy outcomes. Despite the global prevalence of SARS-CoV-2 infection, its maternal–fetal interface during the first trimester remains underexplored. Here, the authors combined a cohort of 700+ samples and determine that maternal SARS-CoV-2 infection in the first trimester rarely infects placental tissue but alters immune responses and cellular communication, which may influence pregnancy outcomes. https://www.nature.com/articles/s41467-026-71770-9