Mucin isoform-microbiome crosstalk shaping the course of COVID-19: a help in patient stratification?

Infection with SARS-CoV-2 mostly leads to a mild self-limiting respiratory tract illness, however, some patients develop severe progressive pneumonia, multiorgan failure, and death. This project aims to determine factors that dictate the course of COVID19 beyond cytokines. We have prior data that specific aberrantly expressed mucins, triggered by SARS-CoV-2, regulate ACE2 expression and affect lung barrier integrity. Such mucin alterations are clinically relevant as excessive mucin production is seen in severe COVID-19 illness obstructing the respiratory tract and complicating recovery. Here, we will first identify differentially expressed mucin isoforms in COVID-19 patients exhibiting the entire spectrum of disease severity. Thereafter, therapeutics currently used for COVID-19 will be screened for their ability to reduce mucin abundance. As mucin expression is also a critical factor in microbiome homeostasis and dysbiosis might modulate COVID-19 severity, this project secondly aims to map the microbiome associated with different degrees of disease severity. Unravelling mucin isoform-microbiome interactions that shape the course of SARS-CoV-2 infection will lead to the future identification of those patients who are in danger of progressing to severe disease. This project will also improve the choice for an appropriate treatment as well as the time frame of treatment options once infection occurs.