The novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic, and resulted in high case-fatality rate in the elderly. In addition to typical respiratory responses, ~50% of clinical cases include gastrointestinal symptoms such as diarrhea, vomiting, abdominal pain, and persistent fecal shedding of the virus even after its clearance from the pulmonary system. In the present study, we assessed aging-associated gut transcriptomic responses considering the gastrointestinal symptoms contributing to COVID-19 severity. Intestinal expression of SARS-CoV-2 receptors and defense biomarkers decreased with increasing age. Moreover, aging-associated integrated stress responses (ISR) and mTOR-linked cell metabolic stress signals counteracted gut defense biomarkers. However, SARS-CoV-2 receptor expression was positively associated with gut barrier integrity potently via downregulation of the two stress-responsive signals. Gut transcriptome-based mechanistic prediction implicates that high susceptibility to COVID-19 in the elderly with low SARS-CoV-2 receptors is due to aging stress-associated defective gut defense, providing a new avenue for viral entry receptor-independent interventions.
【저자키워드】 SARS-CoV-2, aging, Gut barrier, integrated stress responses, metabolic stress, 【초록키워드】 COVID-19, coronavirus, Biomarker, Biomarkers, Stress, susceptibility, COVID-19 severity, novel coronavirus disease, abdominal pain, diarrhea, virus, viral entry, SARS-CoV-2 receptor, global pandemic, response, receptor, expression, fecal, Gut, acute respiratory syndrome, increasing age, downregulation, vomiting, Defense, clearance, Gastrointestinal symptom, transcriptomic, responses, gut barrier integrity, Cell, caused, include, addition, contributing to, expression of SARS-CoV-2, pulmonary system, 【제목키워드】 barrier, Public, insight,