A comprehensive survey of bat sarbecoviruses across China in relation to the origins of SARS-CoV and SARS-CoV-2

SARS-CoV and SARS-CoV-2 have been thought to originate from bats. In this study, we screened pharyngeal and anal swabs from 13 064 bats collected between 2016 and 2021 at 703 locations across China for sarbecoviruses, covering almost all known southern hotspots, and found 146 new bat sarbecoviruses. Phylogenetic analyses of all available sarbecoviruses show that there are three different lineages-L1 as SARS-CoV-related CoVs (SARSr-CoVs), L2 as SARS-CoV-2-related CoVs (SC2r-CoVs) and novel L-R (recombinants of L1 and L2)-present in Rhinolophus pusillus bats, in the mainland of China. Among the 146 sequences, only four are L-Rs. Importantly, none belong in the L2 lineage, indicating that circulation of SC2r-CoVs in China might be very limited. All remaining 142 sequences belong in the L1 lineage, of which YN2020B-G shares the highest overall sequence identity with SARS-CoV (95.8%). The observation suggests endemic circulations of SARSr-CoVs, but not SC2r-CoVs, in bats in China. Geographic analysis of the collection sites in this study, together with all published reports, indicates that SC2r-CoVs may be mainly present in bats of Southeast Asia, including the southern border of Yunnan province, but absent in all other regions within China. In contrast, SARSr-CoVs appear to have broader geographic distribution, with the highest genetic diversity and sequence identity to human sarbecoviruses along the southwest border of China. Our data provide the rationale for further extensive surveys in broader geographical regions within, and beyond, Southeast Asia in order to find the most recent ancestors of human sarbecoviruses.