Interferon-alpha or -beta facilitates SARS-CoV-2 pulmonary vascular infection by inducing ACE2

• DOI: 10.1007/s10456-021-09823-4
• Publication Date: 2021-10-29T10:03:06Z
• Authors: Timothy Klouda; Yuan Hao; Hyunbum Kim; Jiwon Kim; Judith Olejnik; Adam J. Hume; Sowntharya Ayyappan; Xuechong Hong; Juan Melero-Martin; Yinshan Fang; Qiong Wang; Xiaobo Zhou; Elke Mühlberger; Hongpeng Jia; Robert F. Padera; Benjamin A. Raby; Ke Yuan
• Keywords: Viral Pneumonia; Diffuse alveolar damage; Coronavirus

Abstract Severe viral pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized a hyperinflammatory state typified elevated circulating pro-inflammatory cytokines, frequently leading to potentially lethal vascular complications including thromboembolism, disseminated intracellular coagulopathy and vasculitis. Though endothelial infection subsequent damage have been described in patients with fatal COVID-19, mechanism which this occurs remains elusive, particularly given that, under naïve conditions, pulmonary cells demonstrate minimal cell surface expression of SARS-CoV-2 binding receptor ACE2. Herein we describe endothelium postmortem lung samples from individuals who died demonstrating both heterogeneous ACE2 damage. In primary cultures, show that dependent on induction protein process facilitated type 1 interferon-alpha (IFNα) or -beta(β)—two main anti-viral cytokines induced infection—but not significantly other (including interleukin 6 interferon γ/λ). Our findings suggest stereotypical response may paradoxically facilitate propagation COVID-19 epithelium vasculature, raising concerns regarding use exogenous IFNα/β treatment COVID-19.