Consistent Detection of 2019 Novel Coronavirus in Saliva.
Kelvin K. W. To1, Kelvin K. W. To2, Kelvin K. W. To3, Owen Tak Yin Tsang3, Cyril C. Y. Yip1, Cyril C. Y. Yip2, Kwok-Hung Chan2, Tak Chiu Wu4, Jacky Chan3, Wai Shing Leung3, Thomas Shiu Hong Chik3, Chris Yau Chung Choi3, Darshana H. Kandamby, David Christopher Lung4, Anthony Raymond Tam1, Rosana W.S. Poon2, Rosana W.S. Poon1, Agnes Yim Fong Fung2, Ivan Hung1, Vincent C.C. Cheng2, Vincent C.C. Cheng1, Jasper Fuk-Woo Chan2, Jasper Fuk-Woo Chan3, Jasper Fuk-Woo Chan1, Kwok-Yung Yuen2, Kwok-Yung Yuen3, Kwok-Yung Yuen1 •
TL;DR: The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% of patients and Serial saliva viral load monitoring generally showed a declining trend.
Abstract: The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising noninvasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.
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TL;DR: The basic virology of SARS-CoV-2 is described, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail. In this Review, Shi and colleagues summarize the exceptional amount of research that has characterized acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) since this virus has swept around the globe. They discuss what we know so far about the emergence and virology of SARS-CoV-2 and the pathogenesis and treatment of COVID-19.
2,904 citations
Kelvin K. W. To1, Owen Tak Yin Tsang2, Wai Shing Leung2, Anthony Raymond Tam3, Tak Chiu Wu4, David Christopher Lung4, Cyril C. Y. Yip1, Jian Piao Cai1, Jacky Man Chun Chan2, Thomas Shiu Hong Chik2, Daphne Pui-Ling Lau2, Chris Yau Chung Choi2, Lin Lei Chen1, Wan Mui Chan1, Kwok-Hung Chan1, Jonathan Daniel Ip1, Anthony Chin-Ki Ng1, Rosana W.S. Poon1, Cui Ting Luo1, Vincent C.C. Cheng1, Jasper Fuk-Woo Chan2, Jasper Fuk-Woo Chan1, Ivan Hung1, Zhiwei Chen1, Honglin Chen1, Kwok-Yung Yuen2 •
TL;DR: The serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal saliva samples from patients with COVID-19, and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 are ascertained.
Abstract: Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
2,778 citations
Alfonso J. Rodriguez-Morales, Jaime A. Cardona-Ospina, Estefanía Gutiérrez-Ocampo1, Rhuvi Villamizar-Peña1, Yeimer Holguin-Rivera1, Juan Pablo Escalera-Antezana, Lucia Elena Alvarado-Arnez, D. Katterine Bonilla-Aldana1, Carlos Franco-Paredes2, Andrés F. Henao-Martínez2, Alberto Paniz-Mondolfi3, Guillermo J. Lagos-Grisales1, Eduardo Ramírez-Vallejo1, José Antonio Suárez4, Lysien I. Zambrano5, Wilmer E. Villamil-Gómez6, Graciela J. Balbin-Ramon7, Ali A. Rabaan8, Harapan Harapan9, Kuldeep Dhama10, Hiroshi Nishiura11, Hiromitsu Kataoka12, Tauseef Ahmad13, Ranjit Sah14 •
Technological University of Pereira1, University of Colorado Boulder2, Icahn School of Medicine at Mount Sinai3, Instituto Conmemorativo Gorgas de Estudios de la Salud4, Universidad Nacional Autónoma de Honduras5, University of Atlántico6, Scientific University of the South7, Johns Hopkins University8, Syiah Kuala University9, Indian Veterinary Research Institute10, Hokkaido University11, Hamamatsu University School of Medicine12, Southeast University13, Tribhuvan University14
TL;DR: A systematic literature review with meta-analysis was performed using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases, finding that this virus brings a huge burden to healthcare facilities, especially in patients with comorbidities.
1,762 citations
Cites background from "Consistent Detection of 2019 Novel ..."
...Clin Infect Dis 02/12 China Cross-sectional 12 14 [70] COVID-19 team Australia Team Report 02/12 Australia Cross-sectional 15 12 [71]...
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...02/12 12 [70] COVID-19 team Australia 02/12 15 14 (93....
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TL;DR: Dental professionals play great roles in preventing the transmission of 2019-nCoV, and the infection control measures during dental practice are recommended to block the person-to-person transmission routes in dental clinics and hospitals.
Abstract: A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.
1,602 citations
Shufa Zheng, Jian Fan1, Fei Yu1, Baihuan Feng1, Bin Lou1, Qianda Zou1, Guoliang Xie1, Sha Lin1, Ruonan Wang1, Xianzhi Yang1, Weizhen Chen1, Qi Wang1, Dan Feng Zhang1, Yanchao Liu1, Renjie Gong1, Zhaohui Ma1, Siming Lu1, Yanyan Xiao1, Yaxi Gu1, Jinming Zhang1, Hangping Yao1, Kaijin Xu1, Xiaoyang Lu1, Guoqing Wei1, Jianying Zhou1, Qiang Fang1, Hongliu Cai1, Yunqing Qiu1, Jifang Sheng1, Yu Chen, Tingbo Liang1 •
TL;DR: The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.
Abstract: Objective To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. Design Retrospective cohort study. Setting A designated hospital for patients with covid-19 in Zhejiang province, China. Participants 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. Main outcome measures Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed. Results 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P Conclusion The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.
1,271 citations
References
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Chaolin Huang1, Yeming Wang2, Xingwang Li3, Lili Ren4, Jianping Zhao5, Yi Hu5, Li Zhang1, Guohui Fan2, Jiuyang Xu6, Xiaoying Gu2, Zhenshun Cheng7, Ting Yu1, Jia'an Xia1, Yuan Wei1, Wenjuan Wu1, Xuelei Xie1, Wen Yin5, Li Hui2, Min Liu2, Yan Xiao4, Hong Gao4, Li Guo4, Jungang Xie5, Guang-Fa Wang8, Rongmeng Jiang3, Zhancheng Gao8, Qi Jin4, Jianwei Wang4, Bin Cao2 •
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
"Consistent Detection of 2019 Novel ..." refers background in this paper
...In December 2019, a SARS-CoV–like coronavirus, the 2019 novel coronavirus (2019-nCoV), has emerged in Hubei Province of China and has spread rapidly in mainland China and to other parts of the world [2, 3]....
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Jasper Fuk-Woo Chan1, Shuofeng Yuan1, Kin-Hang Kok1, Kelvin K. W. To1, Kelvin K. W. To2, Hin Chu1, Jin Yang2, Fanfan Xing2, Jieling Liu2, Cyril C. Y. Yip1, Rosana W.S. Poon1, Hoi Wah Tsoi1, Simon Kam Fai Lo2, Kwok-Hung Chan1, Vincent Kwok-Man Poon1, Wan Mui Chan1, Jonathan Daniel Ip1, Jian Piao Cai1, Vincent C.C. Cheng1, Honglin Chen1, Honglin Chen2, Christopher K.M. Hui2, Kwok-Yung Yuen2 •
TL;DR: The findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions.
7,392 citations
"Consistent Detection of 2019 Novel ..." refers background or methods in this paper
...In-house 1-step real-time reverse transcription–quantitative polymerase chain reaction (RT-qPCR) assay targeting the S gene of 2019-nCoV was performed using QuantiNova SYBR Green RT-PCR Kit (Qiagen) in a LightCycler 480 Real-Time PCR System (Roche), as we described previously [2]....
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...The 2019-nCoV belongs to Betacoronavirus genus lineage B, and is phylogenetically closely related to bat SARS-like coronaviruses [2]....
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...In December 2019, a SARS-CoV–like coronavirus, the 2019 novel coronavirus (2019-nCoV), has emerged in Hubei Province of China and has spread rapidly in mainland China and to other parts of the world [2, 3]....
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...Furthermore, the collection of nasopharyngeal or oropharyngeal specimens causes discomfort and may cause bleeding, especially in patients with thrombocytopenia [2]....
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Jsm Peiris1, Sik To Lai, Llm Poon1, Yi Guan1, Lyc Yam2, Wilina Lim3, John M. Nicholls1, Wks Yee4, WW Yan, MT Cheung2, V. C. C. Cheng1, KH Chan1, Dnc Tsang5, R Yung2, Ting Kin Ng, KY Yuen1 •
TL;DR: Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.
2,753 citations
TL;DR: Binformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
Abstract: A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
2,403 citations
"Consistent Detection of 2019 Novel ..." refers background in this paper
...In 2003, the severe acute respiratory syndrome coronavirus (SARS-CoV) caused a devastating global outbreak with a casefatality rate of 10% [1]....
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...SARS-CoV has been shown to infect epithelial cells in salivary gland ducts in rhesus macaques [12]....
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...may confer differences in pathogenicity and transmissibility from SARS-CoV [4]....
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...However, the spike, ORF8, and ORF3b proteins differ significantly from other known SARS-like coronaviruses, which may confer differences in pathogenicity and transmissibility from SARS-CoV [4]....
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...In December 2019, a SARS-CoV–like coronavirus, the 2019 novel coronavirus (2019-nCoV), has emerged in Hubei Province of China and has spread rapidly in mainland China and to other parts of the world [2, 3]....
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TL;DR: It is shown that sneezing is rare and not important for—and that coughing is not required for—influenza virus aerosolization, and that upper and lower airway infection are independent and that fine-particle exhaled aerosols reflect infection in the lung.
Abstract: Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1–3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.
432 citations
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