University of Maryland Claude D. Pepper Older Americans Independence Center (UM-OAIC)

ABSTRACT :Identifying patients at risk for severe complications (i.e. respiratory failure, shock, or multiorgan dysfunction)following COVID-19 infection represents a critical challenge. The case fatality rate in COVID-19 indicates thatolder people are dying at a higher rate than other age groups, with 80 percent of deaths occurring in those olderthan 65 years. However, predicting disease severity in COVID-19 patients remains elusive.Humans co-exist with a vast and complex set of microbes (termed the microbiota) that extensively interact withthe immune system and have the ability to trigger pro- or anti-inflammatory responses. Recent studies suggestthat the host immune status is influenced by a fine balance of pro- and anti-inflammatory signals generated, inpart, by the microbiota. This balance is most likely disrupted in patients with severe acute respiratory syndromecoronavirus (SARS-CoV-2). Given that previous studies have shown an association between inflammatory statusof the patient and severity of the COVID-19 infection, characterizing the impact of the microbiota in SARS-CoV-2 infection might prove critical to predict disease severity. The objective of this study is to define the associationbetween the proinflammatory microbiome and the risk of developing ARDS in elderly patients with coronavirusinfection admitted at University of Maryland School of Medicine. Our hypothesis is that pro-inflammatorymicrobiota is associated with airway epithelial destruction leading to severe coronavirus infection. The proposedwork has the potential to identify pathway(s) involved in development of more severe complications of viralinfection which can guide new treatments.This supplemental grant expands the current scope of University of Maryland Claude D. Pepper Center (UM-OAIC) research to identify new and critical microbiota-based targets for diagnostic and therapeutic applications,in order to improve outcomes and decrease disabilities in elderly patients diagnosed with Coronavirus infection.Our long-term goal is to develop novel microbiota-based targets for diagnostic applications and new treatmentsto reduce time on the ventilator, ICU and hospital stay with additional goals of rapid discharge home and returnto a meaningful quality of life. We propose the following specific aims:SA1: Characterize the associations between human microbiota and ARDS in elderly patients infected withcoronavirus.SA2: : Evaluate the T-cell repertoires, cytokine profiles associated with proinflammatory microbiota and ARDSin patients older than 65 in comparison with patients younger than 65 years old.SA3 : Evaluate if a proinflammatory microbiome is associated with worse outcomes (longer hospital length ofstay and time on the ventilator) in comparison with anti-inflammatory microbiome.