A new paper published on EBioMedicine analyzes metagenome contribution to Covid-19 response variability.

A key question concerning COVID-19 is why most infected persons do not develop severe disease, while others become critically ill. This dichotomy is related to age, gender, immunosuppression and comorbidities, but many persons who are young succumb to the virus.

A significant percent of cases develop runaway inflammation and result in sepsis like multi-organ failure and death. Unlike SARS and MERS infections,
COVID-19 manifests in a highly variable response based on the pathophysiological status of the host. The Authors propose that the metagenome directly contributes to this variable response.

Age and metabolic disorders such as obesity and type 2 diabetes
are major risk factors for COVID-19 severity . A common factor
associated with aging and other COVID-19 risk factors is the dysbiosis
of gut microbiota and resulting low grade inflammation with loss of
epithelial barrier function.

The pathogenesis of COVID-19 involves host specific factors that provide a unique window of opportunity for intervention. One possibility is that epithelial destruction caused by the binding of the virus to ACE2 receptors on gut enterocytes adds to the barrier dysfunction associated with comorbidities such as aging, obesity and heart disease. The resulting activation of the immune system due to pathogenic gut microbes results in a nonproductive innate immune response, as well as suppression of the adaptive immune response.

The oral, nasopharyngeal and lung microbiomes may also play a vital role in accelerating COVID-19 pathogenesis. Oral pathogens were directly shown to influence colitis in mouse models, suggesting remote control of inflammation. It is well established that the loss of epithelial barrier function at any mucosal site may initiate systemic dissemination, as well as remote organ destruction. Furthermore, many critically ill COVID19 patients are receiving antibiotics and have drastically altered dietary input, which will both have critical influences on microbial populations in the gut.

The influence of the microbiota on immune processes in COVID19 infection may be assessed with metagenomic analysis of nasal, oral and intestinal communities, as well as metabolomics.