03053nas a2200661   4500000000100000000000100001008004100002260001200043653001200055653002000067653001300087653002500100653002000125653002100145653001500166653002500181653002700206653001600233653001100249653001100260653001100271653002200282653001500304653000900319653001400328653001400342653002100356653005200377653001500429653001500444653001500459653001800474100001300492700001100505700001700516700001800533700001600551700001400567700001500581700001500596700002200611700001200633700001800645700002300663700002100686700002600707700002300733700001900756700002400775700002300799700001700822700001900839245006600858300001400924490000700938520143200945022001402377       2020                            d  c2020-0710aAnimals10aBetacoronavirus10aCOVID-1910aCell Differentiation10aCells, Cultured10aChild, Preschool10aChiroptera10aChlorocebus aethiops10aCoronavirus Infections10aenterocytes10aFemale10aHumans10aInfant10aIntestinal Mucosa10aIntestines10aMale10aorganoids10aPandemics10aPneumonia, Viral10aReverse Transcriptase Polymerase Chain Reaction10aSARS-CoV-210aVero Cells10aViral Load10aViral Tropism1 aJie Zhou1 aCun Li1 aXiaojuan Liu1 aMan Chun Chiu1 aXiaoyu Zhao1 aDong Wang1 aYuxuan Wei1 aAndrew Lee1 aAnna Jinxia Zhang1 aHin Chu1 aJian-Piao Cai1 aCyril Chik-Yan Yip1 aIvy Hau-Yee Chan1 aKenneth Kak-Yuen Wong1 aOwen Tak-Yin Tsang1 aKwok-Hung Chan1 aJasper Fuk-Woo Chan1 aKelvin Kai-Wang To1 aHonglin Chen1 aKwok Yung Yuen00aInfection of bat and human intestinal organoids by SARS-CoV-2  a1077-10830 v263 aA novel coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally1,2. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats1,2. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicus species that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection3,4. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.  a1546-170X