ABSTRACT
This study investigates the systemic inflammatory response in mice infected with a murine coronavirus (MHV), which shares a common genus with SARS-CoV-2, and sustaining a fracture. The study reveals that the combined inflammatory incidents of MHV infection and fracture disrupt the systemic immune response in both female and male mice, likely leading to immune dysregulation, altered cell recruitment, and disruption of the typical inflammatory cascade. Notably, the study uncovers sex-specific responses that modulate circulating immune factors. Females exhibit elevated levels of inflammatory factors, whereas males demonstrate a diminished response. This divergence is mirrored in cell populations, suggesting that the quantity of immune factors released may contribute to these discrepancies. The findings suggest that an overproduction of proinflammatory cytokines may induce a dysregulated immune response, contributing to the observed poorer prognosis in comorbid cases. These insights could pave the way for therapeutic advancements and treatment strategies aimed at reducing mortality rates in COVID-19 patients with fractures.