Myeloid-derived suppressor cells as predictors for severe COVID-19 - longitudinal studies of respiratory and systemic immune responses to SARS-CoV-2 across disease severity

BACKGROUND

Despite intense research efforts in the past year, information on what dictates diseases severity in SARS-CoV-2 infection/COVID-19 disease is still incomplete. Even in light of the COVID-19 vaccines developed at “warp speed”, a more detailed understanding of the immunological responses in COVID-19 is important to combat future virus variants and find treatment strategies in individuals that cannot be vaccinated.

Almost all patients with COVID-19 present with lung involvement, as evidenced by chest radiography, whereas severe complications— such as ARDS and death — are only observed in a subgroup of patients. Despite lung involvement, most studies focus on peripheral blood which is often more accessible. A unique aspect of our work is that we sample the airways as well as blood in COVID-19 patients across disease severity and over time.

We do immunological studies and have identified that myeloid-derived suppressor cells (MDSCs) are elevated in more severely ill COVID-19 patients and that this immune cell subset potentially could be used as a biomarker to identify patients at risk of developing severe disease. AIMS

This proposal is aimed to understand what immune parameters predict COVID-19 disease severity, and whether they can be utilized in the clinic as practical biomarkers. WORKPLAN

Using our cohort and biobank of longitudinal respiratory and blood samples from COVID-19 patients across disease severity, we will extend our studies on MDSC to analyze if protein(s) produced by MDSCs can be identified and used as a biomarker to predict disease severity.

We will investigate how early immune response dictate longterm immunological and non-immunological effects in individuals who have undergone mild, moderate or severe COVID-19. SIGNIFICANCE

Emerging viruses have attracted the world's attention and now more than ever there is a need for innovative and complementary approaches to provide important basic understanding of mechanisms that can circumvent some of the problems when facing virus outbreaks. Human studies are crucial to understand pathogenesis in humans. Here, we do state-of-the-art immunological studies on human respiratory immune cells in clinically well-characterized patients with acute and convalescent disease to determine how they influence disease severity.