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 that older people are dying at a higher rate than other age groups, with 80 percent of deaths occurring in those older than 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 with the immune system and have the ability to trigger pro- or anti-inflammatory responses. Recent studies suggest that the host immune status is influenced by a fine balance of pro- and anti-inflammatory signals generated, in part, by the microbiota. This balance is most likely disrupted in patients with severe acute respiratory syndrome coronavirus (SARS-CoV-2). Given that previous studies have shown an association between inflammatory status of 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 association between the proinflammatory microbiome and the risk of developing ARDS in elderly patients with coronavirus infection admitted at University of Maryland School of Medicine. Our hypothesis is that pro-inflammatory microbiota is associated with airway epithelial destruction leading to severe coronavirus infection. The proposed work has the potential to identify pathway(s) involved in development of more severe complications of viral infection 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 treatments to reduce time on the ventilator, ICU and hospital stay with additional goals of rapid discharge home and return to a meaningful quality of life. We propose the following specific aims: SA1: Characterize the associations between human microbiota and ARDS in elderly patients infected with coronavirus. SA2: : Evaluate the T-cell repertoires, cytokine profiles associated with proinflammatory microbiota and ARDS in 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 of stay and time on the ventilator) in comparison with anti-inflammatory microbiome.