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1.
Virus evolution ; 2022.
Article in English | EuropePMC | ID: covidwho-1898319

ABSTRACT

Over the latest several decades, no emerging virus has had a profound impact on the world as the SARS-CoV-2 emerged at the end of 2019 has done. To know where SARS-CoV-2 is originated from and how it jumped into human population, we immediately started a surveillance investigation in wild mammals in and around Wuhan when we determined the agent. Herein, coronaviruses were screened in the lung, liver, intestinal tissue samples from 15 raccoon dogs, seven Siberian weasels, three hog badger and three Reeves’s muntjacs collected in Wuhan and 334 bats collected around Wuhan. Consequently, eight alphacoronaviruses were identified in raccoon dogs, while nine betacoronaviruses were found in bats. Notably, the newly-discovered alphacoronaviruses shared a high whole genome sequence similarity (97.9%) with the canine coronavirus strain 2020/7 sampled from domestic dog in the United Kingdom. Some of betacoronaviruses identified here were closely related to previously known bat SARS-CoV-related viruses sampled from Hubei province and its neighbors, while remaining betacoronaviruses exhibited a close evolutionary relationship to SARS-CoV-related bat viruses in the RdRp gene tree and clustered together with SARS-CoV-2-related bat coronaviruses in the M, N and S gene trees, but with relatively low similarity. Additionally, these newly-discovered betacoronaviruses seem unlikely to bind angiotensin-converting enzyme 2 (ACE2) because of the deletions in the two key regions of their receptor binding motifs. Finally, we did not find SARS-CoV-2 or its progenitor virus in these animal samples. Due to the high circulation of canine coronaviruses in raccoon dogs in Wuhan, more scientific efforts are warranted to better understand their diversity and evolution in China and the possibility of a potential human agent.

2.
Chin Med J (Engl) ; 133(9): 1039-1043, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722619

ABSTRACT

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/genetics , Pneumonia, Viral/genetics , RNA, Viral/genetics , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/rehabilitation , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/rehabilitation , Real-Time Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2
3.
PLoS Pathog ; 18(2): e1010259, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1690683

ABSTRACT

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen-Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Pneumonia/epidemiology , Respiratory Tract Infections/epidemiology , SARS-CoV-2/isolation & purification , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , COVID-19/virology , China/epidemiology , Cohort Studies , Female , Gene Expression Profiling , Humans , Male , Metagenomics , Middle Aged , Phylogeny , Pneumonia/microbiology , Respiratory Tract Infections/microbiology , Young Adult
4.
BMC Med ; 20(1): 24, 2022 01 20.
Article in English | MEDLINE | ID: covidwho-1638127

ABSTRACT

BACKGROUND: COVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology. METHODS: To better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients. RESULTS: Altered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients. CONCLUSIONS: Our results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Dysbiosis , Homeostasis , Humans , SARS-CoV-2
5.
Virol Sin ; 35(6): 785-792, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1217481

ABSTRACT

Healthcare workers (HCWs) are at high risk of occupational exposure to the new pandemic human coronavirus, SARS-CoV-2, and are a source of nosocomial transmission in airborne infectious isolation rooms (AIIRs). Here, we performed comprehensive environmental contamination surveillance to evaluate the risk of viral transmission in AIIRs with 115 rooms in three buildings at the Shanghai Public Health Clinical Center, Shanghai, during the treatment of 334 patients infected with SARS-CoV-2. The results showed that the risk of airborne transmission of SARS-CoV-2 in AIIRs was low (1.62%, 25/1544) due to the directional airflow and strong environmental hygiene procedures. However, we detected viral RNA on the surface of foot-operated openers and bathroom sinks in AIIRs (viral load: 55.00-3154.50 copies/mL). This might be a source of contamination to connecting corridors and object surfaces through the footwear and gloves used by HCWs. The risk of infection was eliminated by the use of disposable footwear covers and the application of more effective environmental and personal hygiene measures. With the help of effective infection control procedures, none of 290 HCWs was infected when working in the AIIRs at this hospital. This study has provided information pertinent for infection control in AIIRs during the treatment of COVID-19 patients.


Subject(s)
COVID-19/transmission , Environmental Monitoring/methods , Hospitals, Isolation , SARS-CoV-2/isolation & purification , Air Microbiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , China/epidemiology , Cross Infection/transmission , Environmental Microbiology , Health Personnel , Humans , Infection Control/instrumentation , Infection Control/methods , Pandemics/prevention & control , RNA, Viral/isolation & purification , Risk Factors , Viral Load
6.
EMBO J ; 39(24): e105896, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-903069

ABSTRACT

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/pathology , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , Female , Genomics/methods , Humans , Lipoproteins/metabolism , Male , Metabolomics/methods , SARS-CoV-2/physiology , Severity of Illness Index , Viral Load
7.
Nature ; 580(7803): E7, 2020 04.
Article in English | MEDLINE | ID: covidwho-73543

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

8.
Nature ; 579(7798): 265-269, 2020 03.
Article in English | MEDLINE | ID: covidwho-258

ABSTRACT

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.


Subject(s)
Betacoronavirus/classification , Communicable Diseases, Emerging/complications , Communicable Diseases, Emerging/virology , Coronavirus Infections/complications , Coronavirus Infections/virology , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/virology , Adult , Betacoronavirus/genetics , COVID-19 , China , Communicable Diseases, Emerging/diagnostic imaging , Communicable Diseases, Emerging/pathology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/pathology , Genome, Viral/genetics , Humans , Lung/diagnostic imaging , Male , Phylogeny , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/pathology , RNA, Viral/genetics , Recombination, Genetic/genetics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/pathology , Tomography, X-Ray Computed , Whole Genome Sequencing
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