For a yet unknown reason, a substantial share of patients suffering from COVID-19 develop long-lasting neuropsychiatric symptoms ranging from cognitive deficits to mood disorders and/or an extreme fatigue. We previously reported that in non-neural cells, angiotensin-1 converting enzyme 2 ( ACE2 ), the gene coding for the SARS-CoV2 host receptor, harbors tight co-expression links with dopa-decarboxylase ( DDC ), an enzyme involved in the metabolism of dopamine. Here, we mined and integrated data from distinct human expression atlases and found that, among a wide range of tissues and cells, enterocytes of the small intestine express the highest expression levels of ACE2 , DDC and several key genes supporting the metabolism of neurotransmitters. Based on these results, we performed co-expression analyses on a recently published set of RNA-seq data obtained from SARS-CoV2-infected human intestinal organoids. We observed that in SARS-CoV2-infected enterocytes, ACE2 co-regulates not only with DDC but also with a specific group of genes involved in (i) the dopamine/trace amines metabolic pathway, (ii) the absorption of microbiota-derived L-DOPA and (iii) the absorption of neutral amino acids serving as precursors to neurotransmitters. We conclude that in patients with long COVID, a chronic infection and inflammation of small intestine enterocytes might be indirectly responsible for prolonged brain alterations.
【저자키워드】 COVID-19, SARS-CoV2, Brain, Long COVID, enterocytes, trace amines, L-DOPA, monoamine oxidase, 【초록키워드】 Inflammation, ACE2, fatigue, Symptom, metabolism, COVID, Dopamine, cells, Patient, amino acids, pathway, Neuropsychiatric, expression, Neurotransmitters, Amino acid, Analysis, angiotensin, chronic infection, Neutral, enterocytes, L-DOPA, Intestinal Organoids, cognitive, metabolic pathway, tissue, disorders, tissues, expression level, enzyme, host receptor, small intestine, coding, precursors, RNA-seq data, precursor, disorder, Absorption, Express, co-expression, extreme, dopa, highest, responsible, performed, develop, involved, reported, long-lasting, Enterocyte, alterations, DDC, 【제목키워드】 alteration, axis, insight,