Obesity exacerbates cardiac oxidative stress and fibrosis upon coronavirus infection.

Abstract

Coronavirus diseases, particularly COVID-19, been associated with cardiac injury. Given that obesity is a well-known risk factor for severe cases with poorer outcomes, we hypothesized that cardiac involvement in a murine betacoronavirus infection would be exacerbated in pre-obese mice. To test this hypothesis, we fed mice a short-term (4-week) cafeteria diet (Caf), which resulted in increased body fat and mild cardiac histological damage, myocyte hypertrophy and fibrosis. Following the diet, we performed intranasal infection with MHV-A59 and evaluated the lungs and hearts eight days post-infection. In the lungs, infection was acute, caused moderate lung injury and was self-limited in both Chow-fed and Caf-fed mice with similar low viral loads recovered from this tissue. Meanwhile, cardiac fibrosis was significantly exacerbated in the Caf diet mice infected with MHV-A59. We also observed elevated levels of circulating cytokines, TNF and IL-10, as well as increased cardiac oxidative stress, solely in the obese infected mice. In contrast, isolated hearts from lean infected mice showed an increased response to β-adrenergic stimulation, which was damped in the Caf diet infected group. These findings indicate that obesity is a significant risk factor for cardiac issues caused by coronavirus infection by modulating local oxidative stress and systemic inflammation.