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 globally^1,2. 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 bats^1,2. 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, infection^3,4. 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.

Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV–infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3⁺ T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.

The emergence of SARS-CoV-2 has led to the current global coronavirus pandemic and more than one million infections since December 2019. The exact origin of SARS-CoV-2 remains elusive, but the presence of a distinct motif in the S1/S2 junction region suggests possible acquisition of cleavage site(s) in the spike protein that promoted cross-species transmission. Through plaque purification of Vero-E6 cultured SARS-CoV-2, we found a series of variants which contain 15-30-bp deletions (Del-mut) or point mutations respectively at the S1/S2 junction. Examination of the original clinical specimen from which the isolate was derived, and 26 additional SARS-CoV-2 positive clinical specimens, failed to detect this variant. Infection of hamsters shows that one of the variants (Del-mut-1) which carries deletion of 10 amino acids (30 bp) does not cause the body weight loss or more severe pathological changes in the lungs that is associated with wild type virus infection. We suggest that the unique cleavage motif promoting SARS-CoV-2 infection in humans may be under strong selective pressure, given that replication in permissive Vero-E6 cells leads to the loss of this adaptive function. It would be important to screen the prevalence of these variants in asymptomatic infected cases. The potential of the Del-mut variant as an attenuated vaccine or laboratory tool should be evaluated.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is transmitted largely by respiratory droplets or airborne aerosols. Despite being frequently found in the immediate environment and feces of patients, evidence supporting the oral acquisition of SARS-CoV-2 is unavailable. Using the Syrian hamster model, we demonstrate that the severity of pneumonia induced by the intranasal inhalation of SARS-CoV-2 increases with virus inoculum. SARS-CoV-2 retains its infectivity in vitro in simulated human-fed-gastric and fasted-intestinal fluid after 2 h. Oral inoculation with the highest intranasal inoculum (105 PFUs) causes mild pneumonia in 67% (4/6) of the animals, with no weight loss. The lung histopathology score and viral load are significantly lower than those infected by the lowest intranasal inoculum (100 PFUs). However, 83% of the oral infections (10/12 hamsters) have a level of detectable viral shedding from oral swabs and feces similar to that of intranasally infected hamsters. Our findings indicate that the oral acquisition of SARS-CoV-2 can establish subclinical respiratory infection with less efficiency.