TY - JOUR KW - Animals KW - Betacoronavirus KW - COVID-19 KW - Cell Differentiation KW - Cells, Cultured KW - Child, Preschool KW - Chiroptera KW - Chlorocebus aethiops KW - Coronavirus Infections KW - enterocytes KW - Female KW - Humans KW - Infant KW - Intestinal Mucosa KW - Intestines KW - Male KW - organoids KW - Pandemics KW - Pneumonia, Viral KW - Reverse Transcriptase Polymerase Chain Reaction KW - SARS-CoV-2 KW - Vero Cells KW - Viral Load KW - Viral Tropism AU - Jie Zhou AU - Cun Li AU - Xiaojuan Liu AU - Man Chun Chiu AU - Xiaoyu Zhao AU - Dong Wang AU - Yuxuan Wei AU - Andrew Lee AU - Anna Jinxia Zhang AU - Hin Chu AU - Jian-Piao Cai AU - Cyril Chik-Yan Yip AU - Ivy Hau-Yee Chan AU - Kenneth Kak-Yuen Wong AU - Owen Tak-Yin Tsang AU - Kwok-Hung Chan AU - Jasper Fuk-Woo Chan AU - Kelvin Kai-Wang To AU - Honglin Chen AU - Kwok Yung Yuen AB - A 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. BT - Nature Medicine DA - 2020-07 DO - 10.1038/s41591-020-0912-6 IS - 7 LA - eng N2 - A 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. PY - 2020 SP - 1077 EP - 1083 T2 - Nature Medicine TI - Infection of bat and human intestinal organoids by SARS-CoV-2 VL - 26 SN - 1546-170X ER -