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Lung epithelial response to SARS-CoV2 and diabetes
  • +2
  • Deblina Raychaudhuri,
  • Abhishake Lahiri,
  • Yogiraj Ray,
  • Sandip Paul,
  • Dipyaman Ganguly
Deblina Raychaudhuri
Abhishake Lahiri
Yogiraj Ray
Sandip Paul
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Dipyaman Ganguly
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Abstract

In SARS-CoV2 infections causing coronavirus disease-2019 (COVID-19) metabolic co-morbidities portend worse disease outcomes. We aimed at understanding the pathogenetic mechanisms underlying this phenomenon that may differentiate SARS-CoV2 infection from few other respiratory viruses that caused more limited pandemics in the recent past. A meta-analysis, of publicly available gene expression studies on human lung epithelial cells (HLEC) infected with different respiratory viruses, revealed both shared and exclusive transcriptional regulations. In addition, a few key metabolic pathways were found to be exclusively enriched in SARS-CoV2 infection. Systemic metabolic disorders are known to cause similar dysregulations in HLECs, which possibly underlie the predisposition of diabetic individuals to chronic lung diseases. We further performed an integrated analysis of the transcriptome from SARS-CoV2-infected HLECs, COVID-19 bronchoalveolar lavage and autopsied lung transcriptome as well as lung transcriptome from preclinical models of diet-induced obesity, revealing significant overlaps among these key pathways in these discreet contexts. This led us to hypothesize that with underlying metabolic co-morbidities this metabolic dysregulation of the HLECs on SARS-CoV2 infection is aggravated promoting widespread disruption of lung epithelial integrity, driving the worse prognosis. We envisage that any therapeutic agent that can target these key featured pathways, viz. metformin, should be of interest in SARS-CoV2 infection and warrants further studies.