Single-cell atlas of a non-human primate reveals new pathogenic 1 mechanisms of COVID-19 2

Stopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by 51 SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state 52 influence viral entry is fundamental for accelerating therapeutic and preventative 53 approaches. In this endeavor, we profiled the transcriptome at single-cell resolution of nine 54 tissues from a Macaca fascicularis monkey. The distribution of SARS-CoV-2 facilitators, ACE2 55 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, 56 kidney, thyroid and liver. Co-expression analysis identified immunomodulatory proteins such 57 as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. 58 Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link 59 between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 60 expression that could promote viral entry. Our work constitutes a unique resource for 61 understanding SARS-CoV-2 pathophysiology in two phylogenetically close species, which 62 might guide in the development of effective treatments in humans.