Diversity and spillover risk of swine acute diarrhea syndrome and related coronaviruses in China and Southeast Asia

Bats are the reservoir hosts of emerging coronaviruses (CoVs) affecting human and livestock health. We assessed the diversity, evolution, and geographic distribution of two alphacoronaviruses (subgenus <i>Rhinacovirus</i>) with considerable potential for emergence: swine acute diarrhea syndrome coronavirus (SADS-CoV), which has caused large outbreaks in pigs in China and can infect primary human airway epithelial cells <i>in vitro</i>; and the related <i>Rhinolophus bat coronavirus HKU2</i> (HKU2-CoV). Phylogenetic analyses of 523 rhinacovirus sequences from bats in China and Southeast Asia suggest these viruses should be reclassified into at least two distinct CoV species representing two well-supported monophyletic clades. Stronger phylogenetic clustering by sampling location than by host species suggests infrequent long-distance transmission of rhinacoviruses in southern China. Ancestral state reconstruction analysis indicates that <i>R. sinicus/thomasi</i> and <i>R. affinis</i> have played an important role in rhinacovirus evolution in southern China and that <i>R. affinis</i> is the likely reservoir host of SADS-CoV that spilled over into pigs. We used species distribution modeling of <i>Rhinolophus</i> spp. bat hosts of rhinacoviruses, combined with pig and human density data, to identify potential geographic rhinacovirus spillover risk in Southeast Asia. Areas of high pig density within suitable bat habitat exist primarily in southern China and northern Vietnam, and hotspots of the highest human density within suitable bat habitat are primarily along the southern coast of China, Java, and central Thailand. Targeted surveillance of pigs and people in these regions may facilitate the timely detection of bat CoV spillover events and mitigate the risk of future outbreaks.IMPORTANCEBats are the reservoir or ancestral hosts of important emerging coronaviruses affecting people (e.g., SARS-CoV and SARS-CoV-2) and livestock (e.g., PEDV, SADS-CoV). Here, we analyzed 523 genetic sequences of SADS-CoV that caused large-scale die-offs of pigs in China, which is known to be able to infect human cells and related HKU2-CoVs. We used this information to identify the horseshoe bat <i>Rhinolophus affinis</i> as the likely spillover host for the outbreak in pigs, and identified the bat species within which these viruses evolved. We then modeled the distribution of these host species and their overlap with dense human and pig populations to identify the regions where surveillance programs can help identify spillover events and prevent future outbreaks.