Obesity as an amplifier of inflammation and organ injury in SARS-CoV-2 infected patients: prognostic potential and therapeutic target (COBESITAS-19)

Several important studies characterizing SARS-CoV-2 infected patients world-wide have identified that obesity is a risk factor for the development of severe symptoms and the need for mechanical ventilation1–4. One of the largest clinical cohort studies to date found that 78% of hospitalized patients were either overweight or obese1. After correcting for age, sex, ethnicity, social deprivation and well as comorbidities, the risk of dying from SARS-CoV-2 increased by 44% which almost doubled for those with obesity1. These findings also corroborate studies from the US2,4. More recently, obesity was found to associate with severe respiratory failure, prolonged hospitalization and delayed viral clearance5. Early during the pandemic we already recognized that obesity might be a risk factor for ICU admission based on our clinical observations. Obesity is therefore an independent risk factor for severe illness and death. In the Netherlands, 50% of the population are overweight (2019, RIVM) yet 65-72% of adults in the UK and US are overweight which may account for the increased number of deaths as a result of SARS-CoV-2 in those countries. Studies investigating why overweight SARS-CoV-2 patients appear to have more severe symptoms, and more importantly the mechanisms driving respiratory failure in these patients have, to our knowledge, not yet been published. We strongly believe that our approach tackles one of the central drivers of SARS-CoV-2 pathogenesis influencing many secondary cellular responses to infection leading to severe respiratory failure in infected patients. Moreover, obesity can lead to poor vaccine immunogenicity and efficacy therefore even when a vaccine for SARS-CoV-2 is finally available, interventions that tackle the severe symptoms of SARS-CoV-2 in patients will likely still be needed. 
Our interdisciplinary team aims to make an impact on the current COVID-19 situation by identifying the mechanisms and amplifying role of obesity and adipose tissue-derived mediators on the pathophysiology of severe SARS-CoV-2 infection, and how that translates to ICU admission and the need for mechanical ventilation. Once we understand the mechanisms of organ failure, new drug therapies can be developed in order to counteract the severe symptoms thereby reducing not only the number of critically ill patients requiring ICU admission and mechanical ventilation but reducing the number of patients dying as a consequence of SARS-CoV-2.