Identification of microbial factors to modulate immune dysregulation and treat post-COVID-19 syndrome.

Post-COVID-19 syndrome represents a new epidemic within the pandemic, affecting potentially more than 330,000 Canadians. While several studies have described post-COVID-19 symptoms, no studies to date have demonstrated the pathophysiological mechanisms underlying these alarming sequelae. Yet, it is precisely this knowledge that will inform post-COVID-19 management and health care resource planning. Previous studies have demonstrated that the composition of the intestinal microbiota in patients with acute COVID-19 is concordant with disease severity and markers of inflammation and tissue damage. Studies in other viral infections such as HIV, have demonstrated that perturbations of the intestinal microbiota and translocation of intestinal bacteria into blood circulation contribute to inflammation and end-organ damage. We hypothesize that perturbations of the intestinal microbiota caused by COVID-19 infection persist for months following infection, leading to leaky gut and bacterial translocation, which results in persistent inflammation and post-COVID-19 manifestations. We have established the first post-COVID-19 research clinic in Montreal and will therefore synergize with our existing infrastructure to address our hypothesis. Through the study of patients with post-COVID-19 syndrome, patients with resolved COVID-19 and patients who tested negative for COVID-19 we will: 1) define the composition and function of the intestinal microbiota; 2) determine if patients with post-COVID-19 syndrome have a leaky gut by evaluating bacterial translocation from the gut into systemic circulation; 3) determine if patients with post-COVID-19 syndrome have increased systemic inflammation and immune dysregulation. This important study will help uncover a mechanism for post-COVID-19 syndrome, while identifying diagnostic markers and bringing forward new therapies such as probiotics or microbially-derived metabolites as a means to treat this debilitating syndrome.