Multiple-omic analyses reveals limited vertical transmission but alter placenta immune microenvironment after SARS-CoV-2 infection in the first trimester of pregnancy

The ongoing pandemic of COVID-19, caused by SARS-CoV-2, has posed a severe threat to global public health. The virus is known to infect multi-organs, including placenta and trigger a wide spectrum of immune responses and clinical manifestations in human. Yet major knowledge gaps remain about the influence of maternal SARS-CoV-2 infection in gestation and placenta immunity to SARS-CoV-2. To shed light on this, this study collected 761 pairs of tissues of chorion and decidua from Jan 2023 to July 2023. qRT-PCR showed that N gene of one fetus tissue and two placenta samples of the acute infection group were positive, while E and RdRp genes were all negative for all samples. RNA in situ hybridization (FISH) further supported limited signals of viral RNA in these samples. These results supported the limited virus infections in fetus and placenta. No evidence of a classical cytokine storm and stable metabolome profiles in serum cytokine was obseved in the two infected groups, indicating limited effects on matern. However, bulk and sing-cell transcriptome (scRNA-seq) analysis revealed that maternal SARS-CoV-2 infection during early pregnancy leads to a wide range of immune responses in fetal-maternal interface. This further support the limit influence of maternal SARS-CoV-2 infection in gestation and placenta. Overall, based on the large scale of data, our finding provides strong evidence for limited vertical transmission of SARS-CoV-2, but dysregulated cell communication potentially leading to long-term implications for embryo implantation and fetal development in the first trimester of pregnancy.