Mild SARS-CoV-2 maternal infection in mice induces transient offspring neurodevelopmental aberrance

Maternal viral infection during pregnancy has been identified as a risk factor for psychiatric disorders and neurodevelopmental abnormalities in offspring. With cumulative SARS-CoV-2 infections now numbering in the hundreds of millions globally, there is a need to evaluate the effects of maternal SARS-CoV-2 infection on offspring brain development and behavior. We developed a mouse model of mild SARS-CoV-2 infection during pregnancy, where SARS-CoV-2 infection is restricted to the respiratory tract. These mice did not exhibit weight loss despite detectable local and systemic immune responses, including placental inflammation. Characterization of the offspring cerebral cortex revealed transient transcriptomic changes at post-natal day 5 (P5), but no gross alterations in the cytoarchitecture, synaptic density, or microglia abundance. Moreover, we did not detect any significant changes in open field nor novel object recognition tests in P50 offspring born to SARS-CoV-2-infected dams. These results suggest that mild SARS-CoV-2 infection induces transient perturbations to offspring brain development but does not appear to result in long-lasting structural or behavioral deficits. Overall design: SARS-CoV-2 infection or mock infection (PBS) of pregnant dams at embryonic day (E)10. Bullk RNA sequencing of the cerebral cortex of offspring at E15, postnatal day (P) 5, and P30. In addition, bulk RNA sequencing of the placenta 4 days post infection (E14). Included here are both biological replicates (unique mouse litters) and technical replicates (offsprings within a given mouse litter).