Cumulative effect of aging and SARS-CoV2 infection on poor prognosis in the elderly: Insights from transcriptomic analysis of lung and blood

Abstract The ongoing pandemic COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over seven million people worldwide to date. It most commonly affects the respiratory system but can also damage kidney, blood vessels, heart, neurological systems etc. Currently there are no FDA approved prophylactics or therapeutics for COVID-19. Probability of contracting this highly contagious infection is similar across age groups but disease severity and reported global case-fatality rate among aged patients with or without comorbidities are notably higher. We hypothesized that expression of genes that changes during aging, may get further augmented on SARS-CoV-2 infection, leading to severe outcome in elderly patients. To test this, we performed a comparative analysis of transcriptome data from Broncho Alveolar Lavage Fluid (BALF)/lung/blood of healthy aging group with i) COVID-19 patients and; and ii) data of host genes interacting with SARS-COV-2 proteins. We observed i) a significant overlap of gene expression profiles of patients’ BALF and blood respectively with lung and blood of the healthy aging group; ii) this overlap was more pronounced in blood compared to lung; and iii) a similar overlap between host genes interacting with SARS-CoV-2 and transcriptome profile of aging blood but not lung. Pathway enrichment analysis of the resulting overlapping gene sets suggests that SARS-Cov-2 infection alters expression of genes that are involved in pro-inflammatory response, apoptosis, T cell polarization, viral replication suppression etc. that are already dysregulated in the elderly population, this cumulatively may lead to poor prognosis. Of note, eQTLs in these functionally relevant genes may also confer poor outcome even in young patients and this may worsen with age and co-morbidities. Additionally, the higher extent of overlap observed in blood, likely first the report may explain the range of clinical symptoms including high prevalence of blood clots, strokes and heart attack as well as multi-organ failure in severe cases. These leads are preliminary based on a very limited patient dataset, but the model holds promise to be tested as and when more tissue specific patient derived data from different age groups, with varying severity and/or from different populations become available.