Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Daniel J Butler; Christopher Mozsary; Cem Meydan; David C Danko; Jonathan Foox; Joel Rosiene; Alon Shaiber; Ebrahim Afshinnekoo; Matthew MacKay; Fritz J Sedlazeck; Nikolay A Ivanov; Maria A Sierra; Diana Pohle; Michael Zeitz; Vijendra Ramlall; Undina Gisladottir; Craig D Westover; Krista Ryon; Benjamin Young; Chandrima Bhattacharya; Phyllis Ruggiero; Bradley W Langhorst; Nathan A Tanner; Justyn Gawrys; Dmitry Meleshko; Dong Xu; Jenny Xiang; Angelika Iftner; Daniela Bezdan; John Sipley; Lin Cong; Arryn Craney; Priya Velu; Ari Melnick; Iman A Hajirasouliha; Thomas Iftner; Mirella Salvatore; Massimo Loda; Lars F Westblade; Shawn Levy; Melissa Cushing; Nicholas P Tatonetti; Marcin Imielinski; Hanna Rennert; Christopher Mason

Given our observation of increased ACE2 gene expression in patients with high SARS-CoV-2 viral load, we broadly investigated the interplay of receiving pharmacologic angiotensin converting enzyme inhibition (ACEI) for hypertension and clinical features of COVID-19 disease. Since ACE2 expression can be increased in patients taking ACEIs, the observed correlation of viral titer with ACE2 expression may be attributed to the pre-infection use of such inhibitors, which is common in older patients and those with comorbidities (Fang et al., 2020) . To address this, we analyzed an observational cohort of 8,278 patients with suspected SARS-CoV-2 infection from NYPH-CUIMC were analyzed for their usage of ACEIs (4,574 who tested positive). We found that use of ACEIs was strongly associated with testing positive in patients suspected of SARS-CoV-2 infection (Odds Ratio, OR=3.06, and 95% Confidence Interval, CI= 2.38-3.94, p=2.44E -18 ). This result was also consistent when corrected for age, sex, and IL-6, where exposure to ACEIs has an OR=1.54, and when corrected for other reported clinical covariates (1.18-2.01, p=1.41E -03 ); patients exposed to ACEIs were 1.85 (1.40-2.44,p=1.71E -05 ) times more likely to test positive. In the univariate analysis, ACEI usage conferred an increased risk of intubation and mortality for SARS-CoV-2 positive patients ( (Figure 6f) .