Evaluation of the Impact of COVID-19 on Brain Development

It has been observed that SARS-CoV-2 infection during the third trimester of pregnancy leads to cortical changes, including reactive gliosis in the periventricular and subcortical white matter, as observed in newborn babies. This suggests that the infection can affect early processes involved in the formation of the cerebral cortex, such as gliogenesis, and brain connectivity.

Therefore, this study aims to investigate the effects of COVID-19 on the processes of cerebral cortex formation and connectivity using an alternative model of SARS-CoV-2 exposure during development.

To assess this, on Postnatal Day (P) 1, 10 μL of Spike (S) protein (1.7 mg/mL) will be subcutaneously injected into Swiss mice in the Spike group, while  saline will be injected into the vehicle (Veh) group. At P10, the animals' brains will be collected for immunohistochemistry (IHC) analysis to examine the impact of S protein on the number of astrocytes (GFAP+; SOX9+). Additionally, cortical excitability will be assessed by Heat Induced Seizure at P10 through exposure to a controlled temperature between 47-48 °C. The differences between groups will be evaluated using the unpaired Student's t-test.

Our data indicate an increase in astrocytes in the somatosensory cortex, as evidenced by IHC analysis performed on P10 animals using GFAP and SOX9 markers. The SPK group exhibited a higher intensity of GFAP (5.904±1.248; n=3) compared to the Veh (1.492±0.531; n=3) (p=0.0313), along with a greater number of SOX9+ cells in the SPK group (21.94±3.677; n=3) compared to the Veh (10±1.503; n=3) (p=0.0397) in the same region. Behavioral analyses revealed that at P10, the Spike group exhibited a shorter latency (s) to the onset of seizure (219.4±22.1; n=5) compared to the Veh (340±14.56; n=7; p=0.0008).

The data suggest that the S protein increases cortical astrocytic reactivity, potentially leading to an inflammatory environment that can influence brain activity, resulting in hyperexcitability.