Shailendra Verma, Ph.D.

What if we knew how obesity influences the outcome of COVID-19 infection?

The COVID-19 pandemic is caused by the novel SARS-CoV-2 virus, and its rapidly emerging variants continuously pose new threats to public health and socioeconomic stability. The pandemic has impacted the health or well-being of people globally. Despite the significant number of research studies completed since the virus was first characterized, there are still a large number of unknowns regarding the disease. The susceptibility of individuals with obesity to severe COVID-19, evidenced by increased rates of hospitalization and mortality, is an important facet of the pandemic. Therefore, it is imperative to understand the factors caused by or associated with obesity that worsen COVID-19 disease. The results of this study will be useful to develop novel vaccines or therapeutics to prevent and treat COVID-19 in susceptible obese subpopulations.

How does obesity make people more vulnerable to COVID-19 disease? In this research study, we will use an obese mouse model on lean vs high-fat diets to examine a wide spectrum of COVID disease severities ranging from mild to severe. We will infect mice with SARS-CoV-2 (Delta variant), and characterize the infected mice at clinical, virologic, and histopathologic levels at standardized time points after infection. Mice will be monitored for their survival, weight loss, and clinical scores. For virological studies, we will quantify SARS-CoV-2 genomic and sub-genomic RNA and infectious virus levels in vital tissues such as nasal turbinate, lungs, heart, spleen, serum, brain, liver, and kidney by RT-qPCR and plaque assay. For histopathological studies, tissues, heart, kidney, and particularly lungs, liver and pancreas will be evaluated for inflammation, tissue damage, and cellular sources of viral infection by immunohistochemistry. Importantly, we will apply state-of-the-art technique called spatial transcriptomics to visualize genes expressed by various cell types within each tissue, thereby defining the different cell types and gene programs that may be regulating the outcome of SARS-CoV-2 infection in lean vs obese settings. The results of this study will identify crucial immunologic weak spots associated with obesity that are exploited by SARS-CoV-2, and potentially identify drug targets to bolster the immune response.

SPARKing Impact: The results of this study will help us understand why obese individuals are more likely to suffer from severe COVID-19 and may yield new drug targets for treatment of critically ill COVID-19 patients.