Age-related gene expression alterations by SARS-CoV-2 infection contribute to poor prognosis in elderly

Abstract

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide and with notable heterogeneity in its clinical presentation. Probability of contracting this highly contagious infection is similar across age groups but disease severity and fatality among aged patients with or without comorbidities are reportedly higher. Previous studies suggest that age associated transcriptional changes in lung and immune system results in a proinflammatory state and increased susceptibility to infectious lung diseases. Similarly, SARS-CoV-2 infection could augment ageing-related gene expression alterations resulting in severe outcomes in elderly patients. To identify genes that can potentially increase covid-19 disease severity in ageing people, we compared age associated gene expression changes with disease-associated expression changes in lung/BALF and whole blood obtained from publicly available data. We observed (i) a significant overlap of gene expression profiles of patients’ BALF and blood with lung and blood of the healthy group, respectively; (ii) a more pronounced overlap in blood compared to lung; and (iii) a similar overlap between host genes interacting with SARS-CoV-2 and ageing blood transcriptome. Pathway enrichment analysis of overlapping gene sets suggest that infection alters expression of genes already dysregulated in the elderly, which together may lead to poor prognosis. eQTLs in these genes may also confer poor outcome in young patients worsening with age and comorbidities. Further, the pronounced overlap observed in blood may explain clinical symptoms including blood clots, strokes, heart attack, multi-organ failure etc. in severe cases. This model based on a limited patient dataset seems robust and holds promise for testing larger tissue specific datasets from patients with varied severity and across populations. Electronic supplementary material The online version of this article (10.1007/s12041-020-01233-7) contains supplementary material, which is available to authorized users.

Exploiting the molecular basis of age and gender differences in outcomes of SARS-CoV-2 infections

“…Consequently, the study of the intersection between SARS-CoV-2 and ageing-related molecular alterations could augment the understanding of COVID-19, thus improving treatment options [8] . Bhattacharyya et al presented a first analysis based on some preliminary public data reinforcing the rationale that such a possible link exists [5] . The expression of the two human receptors TMPRSS2 and ACE2, which are recognised by the SARS-CoV-2 protein Spike, increases with age in mammals [7] , further suggesting a molecular cause for the more severe COVID-19 symptoms with age.…”

Exploiting Molecular Basis of Age and Gender Differences in Outcomes of SARS-CoV-2 Infections

“…Consequently, the study of the intersection between SARS-CoV-2 and ageing-related molecular alterations could augment the understanding of COVID-19, thus improving treatment options [44]. Bhattacharyya et al presented a first analysis based on some preliminary public data reinforcing the rationale that such a possible link exists [45].…”

The aging whole blood transcriptome reveals a potential role of FASLG in COVID-19

“…Current evidence reports that critically ill patients have elevation in IL-6 levels compared to moderately ill patients [36]; in addition to the in ltration of in ammatory cells, immune cells have been found in patients's lung tissues. Notably, disease-associated transcriptional change in aged whole blood had a more pronounced overlap with control blood in comparison to lung tissue transcriptome [53]. By interacting host genes with SARS-CoV-2 and blood transcriptome, Bhattacharyya and Thelma [53] further suggested that viral infection only alters expression pro le already dysregulated in the elderly, thereby resulting in poor prognosis; these altered blood genes may reinforce the appearance of severe clinical manifestations including strokes, blood clots, and heart failures.…”