ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

Bruna GG Pinto; Antonio ER Oliveira; Youvika Singh; Leandro Jimenez; Andre NA Goncalves; Rodrigo LT Ogava; Rachel Creighton; Jean PS Peron; Helder I Nakaya

Seven lung transcriptome studies of patients with either Chronic Obstructive Pulmonary Disease (COPD) or Pulmonary Arterial Hypertension (PAH), as well as smoking volunteers, compared to individuals who were non-smoking volunteers, were downloaded and used in our meta-analysis (Table S1 ). For each study, we performed differential expression analysis between patients and control individuals (Table S1 ). By combining the p-values obtained in all the seven comparisons, we were able to identify 1,740 and 938 genes that were, respectively, up-and down-regulated in the disease (Figure 2a ). Enrichment analysis using these differentially expressed genes revealed several pathways associated with inflammatory processes, metabolism, and ER stress. Among the pathways enriched with down-regulated genes, there were "vasculogenesis" and "regulation of Notch signaling pathway" (figure 2b). The "viral life cycle" pathway, which describes the processes utilized by viruses to ensure survival and to attach and enter the host cells was enriched with up-regulated genes (Figure 2b ). ACE2 was included in this pathway, as well as 25 other genes (Figure 2c ). One of these genes is RAB1A. Rab GTPases are involved in the replication of many viruses infecting humans [25] , but have not been associated with SARS-CoV-2 life cycle yet. Both TMPRSS2 gene, which is required for SARS-CoV-2 cell entry [5] , and FURIN gene, which cleaves SARS-CoV-2 spike glycoprotein [26] were not differentially expressed in most of the lung transcriptome.