The relationship between inflammation caused by SARS-CoV-2 inactivated virus infection and fetal impairment during mice pregnancy

Several studies showed the ACE2 expression in female reproductive tract and placental tissue, suggests that SARS-CoV-2 infection may lead to pregnancy impairment [1]. SARS-CoV-2 infection can occur through several mechanisms, such as inflammatory responses, oxidative stress, and apoptotic pathways, and this may lead to placental abnormality that is associated with intrauterine growth restriction, fetal decompensation and low birth weight [2]. Thus, the aim of this work is to evaluate the inflammatory process mediated by the SARS-CoV-2 inactivated virus and whether this process can lead to fetal impairment. Female K18-hACE2 transgenic mice were instilled intranasally (5 μL/nostril) with 1x10⁵ PFU of SARS-CoV-2 inactivated virus during the first seven days of pregnancy and on the 18^th day, the cesarean section was performed. After, the blood and lung were collected for hematological analysis and cytokine dosages, respectively. The number of fetuses, reabsorptions and the weighing of the fetuses and their respective placentas were also evaluated. The results were expressed as mean±SD. Statistical analysis was performed by T-test followed by Mann-whitney (*p<0.05). This protocol was approved by CEUA/UFRJ and received the number 93/22. The instillation of SARS-CoV-2 inactivated virus showed significant increase in the inflammatory cytokines in lung homogenate, as showed: Tnf-α: 16.3±2.4 pg/μg of protein; IL-6: 7.0±1.4 pg/μg of protein; and IFN-γ: 17.6±2.9 pg/μg of protein, when compared to vehicle group: 10.6±0.9 pg/μg of protein; 4.7±0.7 pg/μg of protein; 12.0±1.5 pg/μg of protein, respectively. Furthermore, the instillation with virus reduced placental efficiency in 66% of pregnant mice (8.8±2.4) when compared to pregnant mice from the vehicle group, 14.1±0.8. These results suggest that instillation of the SARS-CoV-2 inactivated virus caused an inflammatory process and can lead fetal impairment.

[1]Mol.Hum Reprod.(2020)26:367

[2]Am.J.Obstet Gynecol MFM.(2021)3:100468