See Covering the Cover synopsis on page 4.BACKGROUND & AIMS: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has been characterized by fever, respiratory, and gastrointestinal symptoms as well as shedding of virus RNA into feces. We performed a systematic review and meta-analysis of published gastrointestinal symptoms and detection of virus in stool and also summarized data from a cohort of patients with COVID-19 in Hong Kong. METHODS: We collected data from the cohort of patients with COVID-19 in Hong Kong (N ¼ 59; diagnosis from February 2 through February 29, 2020),and searched PubMed, Embase, Cochrane, and 3 Chinese databases through March 11, 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms (loss of appetite, nausea, vomiting, diarrhea, and abdominal pain or discomfort) using a random effects model. RESULTS: Among the 59 patients with COVID-19 in Hong Kong, 15 patients (25.4%) had gastrointestinal symptoms, and 9 patients (15.3%) had stool that tested positive for virus RNA. Stool viral RNA was detected in 38.5% and 8.7% among those with and without diarrhea, respectively (P ¼ .02). The median fecal viral load was 5.1 log 10 copies per milliliter in patients with diarrhea vs 3.9 log 10 copies per milliliter in patients without diarrhea (P ¼ .06). In a meta-analysis of 60 studies comprising 4243 patients, the pooled prevalence of all gastrointestinal symptoms was 17.6% (95% confidence interval [CI], 12.3-24.5); 11.8% of patients with nonsevere COVID-19 had gastrointestinal symptoms (95% CI, 4.1-29.1), and 17.1% of patients with severe COVID-19 had gastrointestinal symptoms (95% CI, 6.9-36.7). In the meta-analysis, the pooled prevalence of stool samples that were positive for virus RNA was 48.1% (95% CI, 38.3-57.9); of these samples, 70.3%Gastroenterology 2020;159:81-95 CLINICAL AT of those collected after loss of virus from respiratory specimens tested positive for the virus (95% CI, 49.6-85.1). CONCLUSIONS: In an analysis of data from the Hong Kong cohort of patients with COVID-19 and a meta-analysis of findings from publications, we found that 17.6% of patients with COVID-19 had gastrointestinal symptoms. Virus RNA was detected in stool samples from 48.1% patients, even in stool collected after respiratory samples had negative test results. Health care workers should therefore exercise caution in collecting fecal samples or performing endoscopic procedures in patients with COVID-19, even during patient recovery.

SARS-CoV-2 has affected over 9 million patients with more than 460,000 deaths in about 6 months. Understanding the factors that contribute to e cient SARS-CoV-2 infection of human cells, which are not previously reported, may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we reported key host and viral determinants that were essential for e cient SARS-CoV-2 infection in the human lung. First, we identi ed heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Second, we demonstrated that while cell surface sialic acids signi cantly restricted SARS-CoV infection, SARS-CoV-2 could largely overcome sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissue explants. Third, we demonstrated that the inserted furin-like cleavage site in SARS-CoV-2 spike was required for e cient virus replication in human lung but not intestine tissues. Overall, these ndings contributed to our understanding on e cient SARS-CoV-2 infection of human lungs.

39 On 31 st December 2019, the World Health Organization was informed of a cluster of cases of 40 pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel 41 coronavirus, now named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 42 from the affected patients. Highly sensitive and specific laboratory diagnostics are important for 43 controlling the rapidly evolving SARS-CoV-2-associated Coronavirus Disease 2019 (COVID-44 19) epidemic. In this study, we developed and compared the performance of three novel real-time 45 RT-PCR assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), 46 and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay which is 47 used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel 48 assay had the lowest limit of detection in vitro (1.8 TCID 50 /ml with genomic RNA and 11.2 RNA 49 copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with 50 laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-51 19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an 52 additional 42 RdRd-P2-negative specimens [119/273 (43.6%) vs 77/273 (28.2%), P<0.001], 53including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract 54 specimens. The mean viral load of these specimens was 3.21×10 4 RNA copies/ml (range, 55 2.21×10 2 to 4.71×10 5 RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with 56 other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical 57 specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly 58 sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis 59 of COVID-19. 60 61 on March 16, 2020 by guest http://jcm.asm.org/ Downloaded from 4