Dynamics of SARS-CoV-2 and Klebsiella pneumoniae

SARS-CoV-2 patients have been reported to have high rates of secondary Klebsiella pneumoniae infections. K. pneumoniae is a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person's immune system is compromised. Despite a high number of K. pneumoniae cases reported in SARS-CoV-2 patients, a coinfection animal model evaluating the pathogenesis is not available. Therefore, we developed a mouse model to study the disease pathogenesis of SARS-CoV-2 and K. pneumoniae co-infection. We also made a model looking at different SARS-CoV-2 severity and K. pneumoniae strains. We also tested at what days post virus infection, K. pneumoniae will increase mortality in co-infected mice. BALB/cJ mice were inoculated with mouse-adapted (MA) SARS-CoV-2 followed by a challenge with K. pneumoniae. Mice were monitored for body weight change, clinical signs, and survival during infection. The bacterial load, viral titers, immune cell accumulation and phenotype, and histopathology were evaluated in lungs. The coinfected mice showed severe clinical disease and a higher mortality rate within 24-48 h of K. pneumoniae infection. The co-infected mice had significantly elevated bacterial load in the lungs, however, viral loads differed between different doses of SARS-CoV-2 and K. pneumoniae strains. Histopathology of co-infected mice showed severe bronchointerstitial pneumonia with copious intralesional bacteria. Flow cytometry analysis showed significantly higher numbers of neutrophils and macrophages in the lungs. Our data points to higher severity of SARS-CoV-2 and high pathogenic strain of K. pneumoniae increases mortality rates.