The impact of SARS-CoV-2 Spike protein on brain development

The Spike (S) protein of SARS-CoV-2 virus is associated with neurological complications that persist beyond the acute phase of infection. Previous studies suggest vertical transmission of the virus, which may affect fetal brain development, increasing the risk of neurological diseases in the future. This confirmatory research aims to evaluate whether exposure to protein S during brain development leads to behavioral and molecular changes. We used Swiss mice, in which protein S was administered by subcutaneous injection at P1 (10µl-1µg/µl), with a control group receiving saline solution (10µl). To assess the presence of inflammatory mediators and  the Toll-like receptor 4 (TLR4), a qPCR was performed for COX-2, IL-10 and TLR4 in the cortex of the animals over 21 days post-injection. Additionally, to assess late cognitive damage at P70, the animals were subjected to novel object recognition test (NOR) (evaluation of declarative memory) and social interaction (evaluation of sociability). Over 21 days post-injection, qPCR analyses indicated increased mRNA expression of COX-2, IL-10 and TLR4 in mice exposed to the Spike protein (n=3/group; p<0,05. In the NOR , males exposed to spike protein failed to recognize the novel object, suggesting a memory impairment (n=10/group; p<0.05). Furthermore, social assessments indicated an impairment in females who received S (n=10/group;**p<0.01). These data suggest that Spike protein may cause an increase in inflammatory mediators and TLR4 in the cerebral cortex, indicating an activation of the immune system, and even affect memory and social behavior in animals exposed to S protein at final stages of brain development.