Abstract
COVID-19 is characterized by a dysregulated and excessive inflammatory response and, in severe cases, acute respiratory distress syndrome. We have recently demonstrated a previously unknown high-affinity interaction between the SARS-CoV-2 spike (S) protein and bacterial lipopolysaccharide (LPS), leading to the boosting of inflammation. Here we present a mouse inflammation model employing the coadministration of aerosolized S protein together with LPS to the lungs. Using NF-κB-RE-Luc reporter and C57BL/6 mice followed by combinations of bioimaging, cytokine, chemokine, fluorescence-activated cell sorting, and histochemistry analyses, we show that the model yields severe pulmonary inflammation and a cytokine profile similar to that observed in COVID-19. Therefore, the model offers utility for analyses of the pathophysiological features of COVID-19 and the development of new treatments.
Highlights
COVID-19 is characterized by a dysregulated and excessive inflammatory response and, in severe cases, acute respiratory distress syndrome
It is of note that at present, no mouse model recapitulates all aspects of COVID-19 in humans, especially pulmonary vascular disease and acute respiratory distress syndrome (ARDS)
The clinical symptoms of patients with ARDS in many ways correspond to the pathophysiology seen during severe COVID-19 disease
Summary
COVID-19 is characterized by a dysregulated and excessive inflammatory response and, in severe cases, acute respiratory distress syndrome. We present a mouse model employing the coadministration of the aerosolized SARS-CoV-2 S protein and bacterial LPS to the lungs, producing severe pulmonary inflammation and a cytokine profile sharing features observed during COVID-19 disease progression. When a combination of 5 μg of S protein and 2 μg of LPS was delivered to the lungs of the mice, we observed a significantly increased NF-κB induction (Figure 1B).
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