RESUMO
The COVID-19 pandemic has affected more than 10 million people worldwide with mortality exceeding half a million patients. Risk factors associated with severe disease and mortality include advanced age,hypertension, diabetes, and obesity. Clear mechanistic understanding of how these comorbidities converge to enable severe infection is lacking. Notably each of these risk factors pathologically disrupts the lipidome and this disruption may be a unifying feature of severe COVID-19. Here we provide the first in depth interrogation of lipidomic changes, including structural-lipids as well as the eicosanoids and docosanoids lipid mediators (LMs), that mark COVID-19 disease severity. Our data reveal that progression from moderate to severe disease is marked by a loss of specific immune regulatory LMs and increased pro-inflammatory species. Given the important immune regulatory role of LMs, these data provide mechanistic insight into the immune balance in COVID-19 and potential targets for therapy with currently approved pharmaceuticals.
RESUMO
The COVID-19 pandemic has affected more than 10 million people worldwide with mortality exceeding half a million patients. Risk factors associated with severe disease and mortality include advanced age, hypertension, diabetes, and obesity.1 Clear mechanistic understanding of how these comorbidities converge to enable severe infection is lacking. Notably each of these risk factors pathologically disrupts the lipidome and this disruption may be a unifying feature of severe COVID-19.1-7 Here we provide the first in depth interrogation of lipidomic changes, including structural-lipids as well as the eicosanoids and docosanoids lipid mediators (LMs), that mark COVID-19 disease severity. Our data reveal that progression from moderate to severe disease is marked by a loss of specific immune regulatory LMs and increased pro-inflammatory species. Given the important immune regulatory role of LMs, these data provide mechanistic insight into the immune balance in COVID-19 and potential targets for therapy with currently approved pharmaceuticals.8.