Inactivated SARS-CoV-2 Exposure Induces Inflammation and Impairs Reproductive Outcomes in Mice

Abstract

COVID-19 has been associated with reproductive dysfunction, although the underlying mechanisms remain unclear. Here, we investigated the effects of inactivated SARS-CoV-2 (iSARS-CoV-2) exposure on reproductive outcomes in K18-hACE2 mice. Pregnant females exposed during early gestation showed reduced fetal number, increased resorptions and decreased placental efficiency. These alterations were associated with pulmonary inflammation, characterized by elevated TNF-α, IL-6 and IFN-γ levels and histopathological damage. In males, exposure impaired the sperm count, motility and reproductive performance, and negatively affected pregnancy outcomes in untreated females. Notably, inflammatory responses occurred in the absence of viral replication, indicating that viral components can trigger systemic effects. Together, these findings demonstrate that inactivated SARS-CoV-2 induces inflammation that compromises fertility and gestational success in both sexes.