A recent study published in Nature Communications reports on Apr. 14 that SARS-CoV-2 is rarely detected in placental tissue during the first trimester of pregnancy, but maternal infection can still disrupt immune signaling at the site where pregnancy begins.
This finding is significant because it suggests that while direct in utero transmission of the virus appears uncommon early in pregnancy, changes to local immune activity and placental function could potentially affect outcomes for pregnant individuals.
Researchers analyzed 761 first-trimester samples from individuals undergoing elective surgical pregnancy termination within 13 weeks of gestation. The study period covered two waves of COVID-19 infections after China lifted strict containment policies. Participants who had been vaccinated within six months or had severe prior infection were excluded to reduce confounding factors. Molecular testing showed only minimal presence of viral material, with low-level N gene signals found in three samples and no evidence for other viral genes, suggesting incomplete viral genomes rather than active infection.
Despite limited detection of the virus itself, further analyses revealed notable alterations at the maternal-fetal interface. Immune profiling indicated increased activation and infiltration by immune cells, upregulation of interferon-stimulated genes, and changes in macrophage populations. Disruption was also seen in pathways involved with cell signaling and angiogenesis, which may impact placental development and trophoblast function.
Serological tests classified participants into acute (IgM-positive), convalescent (IgG-positive), and uninfected groups. Acute infections were linked to higher levels of pro-inflammatory cytokines such as interleukin-31 and growth-regulated oncogene-alpha. In contrast, convalescent samples showed more anti-inflammatory markers like IL-10. Importantly, IgG antibody levels were inversely related to tumor necrosis factor-beta (TNF-β), suggesting a possible protective effect from adaptive immunity—an observation supporting preconception vaccination according to the authors.
While most cases studied were mild or asymptomatic—and thus may not reflect risks associated with severe disease—the authors note limitations including uncertainty about exact timing of infection and small sample sizes for some analyses such as single-cell RNA sequencing.
The researchers conclude that although SARS-CoV-2 does not often directly infect early placental tissue, even limited exposure can trigger substantial local immune changes that might influence maternal-fetal health outcomes.
