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2.
Emerg Microbes Infect ; 11(1): 567-572, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1642256

ABSTRACT

Global concern has been raised by the emergence and rapid transmission of the heavily mutated SARS-CoV-2 Omicron variant (B.1.1.529). So far, the infection features and immune escape ability of the Omicron variant have not been extensively studied. Here, we produced the Omicron pseudovirus and compared its entry, membrane fusion, and immune escape efficiency with the original strain and the dominating Delta variant. We found the Omicron variant showed slightly higher infectivity than the Delta variant and a similar ability to compete with the Delta variant in using Angiotensin-converting enzyme 2 (ACE2) in a BHK21-ACE2 cell line. However, the Omicron showed a significantly reduced fusogenicity than the original strain and the Delta variant in both BHK21-ACE2 and Vero-E6 cells. The neutralization assay testing the Wuhan convalescents' sera one-year post-infection showed a more dramatic reduction (10.15 fold) of neutralization against the Omicron variant than the Delta variant (1.79 fold) compared with the original strain with D614G. Notably, immune-boosting through three vaccine shots significantly improved the convalescents' immunity against the Omicron variants. Our results reveal a reduced fusogenicity and a striking immune escape ability of the Omicron variant, highlighting the importance of booster shots against the challenge of the SARS-CoV-2 antigenic drift.


Subject(s)
COVID-19 , SARS-CoV-2/immunology , Animals , COVID-19/immunology , Chlorocebus aethiops , Humans , Immune Evasion , Immunization, Secondary , Vero Cells
3.
Innovation (N Y) ; 3(1): 100181, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1595417

ABSTRACT

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulin G (IgG) was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

4.
Nat Commun ; 12(1): 5026, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1363491

ABSTRACT

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients' demography, geographic locations and season of illness in China.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/microbiology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Virus Diseases/virology , Viruses/isolation & purification , Adolescent , Adult , Bacteria/classification , Bacteria/genetics , Bacterial Infections/epidemiology , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Prospective Studies , Respiratory Tract Infections/epidemiology , Seasons , Virus Diseases/epidemiology , Viruses/classification , Viruses/genetics , Young Adult
5.
Clinica Chimica Acta ; 505:172-175, 2020.
Article in English | CAB Abstracts | ID: covidwho-1408674

ABSTRACT

Background: There's an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak.

6.
Protein Cell ; 2020 Nov 09.
Article in English | MEDLINE | ID: covidwho-915250

ABSTRACT

In the original publication the author's name 'Dimitri Lavillete' is published incorrectly. The correct author name should be spelt as 'Dimitri Lavillette' is provided in this correction.

8.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-587

ABSTRACT

Circulating in China and 75 other countries and territories, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public h

9.
Protein Cell ; 11(10): 723-739, 2020 10.
Article in English | MEDLINE | ID: covidwho-697126

ABSTRACT

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Oxidoreductases/antagonists & inhibitors , Pandemics , Pneumonia, Viral/drug therapy , RNA Viruses/drug effects , Thiazoles/pharmacology , Animals , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/physiology , Binding Sites/drug effects , COVID-19 , Cell Line , Coronavirus Infections/virology , Crotonates/pharmacology , Cytokine Release Syndrome/drug therapy , Drug Evaluation, Preclinical , Gene Knockout Techniques , Humans , Hydroxybutyrates , Influenza A virus/drug effects , Leflunomide/pharmacology , Mice , Mice, Inbred BALB C , Nitriles , Orthomyxoviridae Infections/drug therapy , Oseltamivir/therapeutic use , Oxidoreductases/metabolism , Oxidoreductases Acting on CH-CH Group Donors , Pneumonia, Viral/virology , Protein Binding/drug effects , Pyrimidines/biosynthesis , RNA Viruses/physiology , SARS-CoV-2 , Structure-Activity Relationship , Thiazoles/therapeutic use , Toluidines/pharmacology , Ubiquinone/metabolism , Virus Replication/drug effects
10.
Emerg Infect Dis ; 26(11): 2755-2758, 2020 11.
Article in English | MEDLINE | ID: covidwho-647120

ABSTRACT

During January-February 2020, coronavirus disease (COVID-19) and tuberculosis were diagnosed for 3 patients in Wuhan, China. All 3 patients had COVID-19 pneumonia. One severely ill patient died after acute respiratory distress syndrome developed. Clinicians and public health officials should be aware of underlying chronic infections such as tuberculosis in COVID-19 patients.


Subject(s)
Betacoronavirus , Coinfection/microbiology , Coronavirus Infections/microbiology , Mycobacterium , Pneumonia, Viral/microbiology , Tuberculosis, Pulmonary/microbiology , Adult , COVID-19 , China , Fatal Outcome , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2
11.
Emerg Microbes Infect ; 9(1): 1259-1268, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-342833

ABSTRACT

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection of ddPCR is significantly lower than that of RT-PCR. We further explored the feasibility of ddPCR to detect SARS-CoV-2 RNA from 77 patients, and compared with RT-PCR in terms of the diagnostic accuracy based on the results of follow-up survey. 26 patients of COVID-19 with negative RT-PCR reports were reported as positive by ddPCR. The sensitivity, specificity, PPV, NPV, negative likelihood ratio (NLR) and accuracy were improved from 40% (95% CI: 27-55%), 100% (95% CI: 54-100%), 100%, 16% (95% CI: 13-19%), 0.6 (95% CI: 0.48-0.75) and 47% (95% CI: 33-60%) for RT-PCR to 94% (95% CI: 83-99%), 100% (95% CI: 48-100%), 100%, 63% (95% CI: 36-83%), 0.06 (95% CI: 0.02-0.18), and 95% (95% CI: 84-99%) for ddPCR, respectively. Moreover, 6/14 (42.9%) convalescents were detected as positive by ddPCR at 5-12 days post discharge. Overall, ddPCR shows superiority for clinical diagnosis of SARS-CoV-2 to reduce the false negative reports, which could be a powerful complement to the RT-PCR.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , COVID-19 , False Negative Reactions , Humans , Limit of Detection , Pandemics , RNA, Viral/genetics , SARS-CoV-2 , Viral Load/methods
12.
Nature ; 582(7813): 557-560, 2020 06.
Article in English | MEDLINE | ID: covidwho-137432

ABSTRACT

The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood1-3. Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding; this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions; however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.


Subject(s)
Aerosols/analysis , Aerosols/chemistry , Bathroom Equipment , Betacoronavirus/isolation & purification , Coronavirus Infections/virology , Hospitals , Pneumonia, Viral/virology , Workplace , Betacoronavirus/genetics , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Crowding , Disinfection , Humans , Intensive Care Units , Masks , Medical Staff , Pandemics/prevention & control , Patients/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , RNA, Viral/analysis , SARS-CoV-2 , Social Isolation , Ventilation
13.
Emerg Microbes Infect ; 9(1): 761-770, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-29222

ABSTRACT

Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.


Subject(s)
Bronchoalveolar Lavage Fluid , Chemokines/analysis , Coronavirus Infections/genetics , Cytokines/analysis , Leukocytes, Mononuclear , Pneumonia, Viral/genetics , Transcriptome , Apoptosis , Betacoronavirus , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Humans , Lymphopenia , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , RNA-Seq , SARS-CoV-2 , Signal Transduction , Tumor Suppressor Protein p53
15.
Clin Chim Acta ; 505: 172-175, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-5447

ABSTRACT

BACKGROUND: There's an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. METHODS: 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. RESULTS: The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. CONCLUSIONS: Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/chemistry , Coronavirus Infections/diagnosis , DNA, Viral/analysis , Pneumonia, Viral/diagnosis , Real-Time Polymerase Chain Reaction/methods , Adolescent , Adult , Age Factors , Aged , Bronchoalveolar Lavage Fluid/virology , COVID-19 , COVID-19 Testing , China/epidemiology , Clinical Laboratory Techniques , Coronavirus Infections/epidemiology , Disease Outbreaks , Female , Humans , Male , Middle Aged , Nucleocapsid/chemistry , Nucleocapsid/genetics , Pandemics , Pneumonia, Viral/epidemiology , Respiratory System/virology , Risk Factors , SARS-CoV-2 , Sex Factors , Sputum/virology , Young Adult
16.
Emerg Microbes Infect ; 9(1): 313-319, 2020.
Article in English | MEDLINE | ID: covidwho-337

ABSTRACT

From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into ß-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Disease Outbreaks , Pneumonia, Viral/epidemiology , Adult , COVID-19 , China , Female , Genome, Viral , Humans , Male , Phylogeny , RNA, Viral/genetics , SARS-CoV-2 , Young Adult
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