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1.
J Med Virol ; 2020 Sep 16.
Article in English | MEDLINE | ID: covidwho-1196488

ABSTRACT

Coronaviruses (CoVs) are nonsegmented, single-stranded, positive-sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.

2.
J Med Virol ; 2020 Sep 05.
Article in English | MEDLINE | ID: covidwho-1196477

ABSTRACT

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and lives. The virus is still spreading throughout the world, and the cumulative number of confirmed cases is increasing. After patients with COVID-19 are treated and discharged, some have repeated clinical symptoms and become positive for nucleic acid tests a second time. Through analysis and review of the existing literature, the proportion of repositive patients in the discharged patient population and their clinical characteristics were systematically described for the first time. Furthermore, an in-depth analysis of the causes of repositive nucleic acid tests and the potential transmission of the disease provides the basis for the management and protection of discharged patients with COVID-19.

3.
Front Immunol ; 11: 602256, 2020.
Article in English | MEDLINE | ID: covidwho-1021889

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, and has been pandemic since March 2020 and led to many fatalities. Vaccines represent the most efficient means to control and stop the pandemic of COVID-19. However, currently there is no effective COVID-19 vaccine approved to use worldwide except for two human adenovirus vector vaccines, three inactivated vaccines, and one peptide vaccine for early or limited use in China and Russia. Safe and effective vaccines against COVID-19 are in urgent need. Researchers around the world are developing 213 COVID-19 candidate vaccines, among which 44 are in human trials. In this review, we summarize and analyze vaccine progress against SARS-CoV, Middle-East respiratory syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, including inactivated vaccines, live attenuated vaccines, subunit vaccines, virus like particles, nucleic acid vaccines, and viral vector vaccines. As SARS-CoV-2, SARS-CoV, and MERS-CoV share the common genus, Betacoronavirus, this review of the major research progress will provide a reference and new insights into the COVID-19 vaccine design and development.


Subject(s)
/prevention & control , Vaccines , Animals , Antibody-Dependent Enhancement , Humans , /physiology
4.
Viruses ; 13(1)2020 12 30.
Article in English | MEDLINE | ID: covidwho-1011626

ABSTRACT

SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-ß) production. N protein repressed IFN-ß production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-ß production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-ß response through targeting the initial step, potentially the cellular PRR-RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-ß production by interfering with RIG-I.


Subject(s)
/immunology , DEAD Box Protein 58/metabolism , Interferon-beta/metabolism , Nucleocapsid Proteins/metabolism , /metabolism , A549 Cells , Animals , DEAD Box Protein 58/genetics , HEK293 Cells , HeLa Cells , Host-Pathogen Interactions/immunology , Humans , Protein Interaction Domains and Motifs , Signal Transduction
5.
J Med Virol ; 92(10): 1938-1947, 2020 10.
Article in English | MEDLINE | ID: covidwho-967766

ABSTRACT

BACKGROUND: With the effective prevention and control of COVID-19 in China, the number of cured cases has increased significantly. Further monitoring of the disease prognosis and effective control of the "relapse" of the epidemic has become the next focus of work. This study analysed the clinical prognosis of discharged COVID-19 patients by monitoring their SAR-CoV-2 nucleic acid status, which provided a theoretical basis for medical institutions to formulate discharge standards and follow-up management for COVID-19 patients. METHODS: We included 13 discharged COVID-19 patients who were quarantined for 4 weeks at home. The patient's daily clinical signs were recorded and sputum and faecal specimens were regularly sent for detection of SARS-CoV-2 nucleic acid. RESULTS: The time between initial symptoms and meeting discharge criteria was 18 to 44 days with an average of 25 ± 6 days. The faecal samples of two patients still tested positive after meeting the discharge criteria and the sputum samples of four patients returned positive 5 to 14 days after discharge. The rate of the recurring positive test result in samples from the respiratory system was 31% (4/13). CONCLUSION: Under the present discharge criteria, the high presence of SARS-CoV-2 nucleic acid in faecal and respiratory samples of discharged COVID-19 patients indicates potential infectivity. Therefore, we suggest that faecal virus nucleic acid should be tested as a routine monitoring index for COVID-19 and a negative result be added to the criteria. Simultaneously, we should strengthen the regular follow-up of discharged patients with continuous monitoring of the recurrence of viral nucleic acid.

6.
Front Oncol ; 10: 1272, 2020.
Article in English | MEDLINE | ID: covidwho-853981

ABSTRACT

Background: A recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), which began in Wuhan, China, with a high level of human-to-human transmission has been reported. There are limited data available on Coronavirus Disease 2019 (COVID-19) patients with hematological malignancies with more than 60 days of follow-up. This study describes the clinical characteristics, including multiple recurrences of COVID-19, in a patient with chronic lymphocytic leukemia (CLL) during 69 days of follow-up. Case Presentation: A 72-year-old female was admitted to hospital isolation after being infected with COVID-19 as part of a family cluster on January 30, 2020. Apart from SARS-Cov-2 virus infection, laboratory results revealed lymphocytosis of uncertain etiology and abnormal distribution of T lymphocytes. On blood smears, small blue lymphocytes with scant cytoplasm were observed, and the presence of high levels of circulating clonal B cells was also demonstrated by flow cytometry. The patient was diagnosed with COVID-19 and CLL. Among her family members, she had the highest viral loads and the fastest progression on lung injury and developed severe pneumonia. Serological results showed she had both 2019-nCoV-specific IgM and IgG antibodies; however, only IgG antibodies were detected in her husband's plasma. Results: A combination regimen of antiviral therapy and high-dose intravenous immunoglobulin (IVIG) in the early stage seemed to be effective for treating CLL and SARS-Cov-2 infection. Because of the low humoral immune response, the CLL patient could not effectively clear the SARS-Cov-2 infection and suffered from recurrence twice during the 69-day follow-up. Conclusion: In CLL, a neoplastic antigen-specific B-cell clone proliferates, and the progeny cells accumulate and outgrow other B cells, leading to immune deficiency. Considering the low humoral immune response and ineffective clearance of SARS-Cov-2 in CLL patients, the follow-up and home quarantine period should be extended. We need further studies to clarify suspending or continuing CLL therapy during COVID infection. For those patients who are prone to progression to severe disease, administering humoral immunity therapies can help to prevent disease progression and quickly meet the cure criteria.

7.
J Med Virol ; 92(4): 424-432, 2020 04.
Article in English | MEDLINE | ID: covidwho-827679

ABSTRACT

Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.


Subject(s)
Coronavirus Infections/immunology , Coronavirus/immunology , Adaptive Immunity , Animals , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , B-Lymphocytes/immunology , Coronavirus/classification , Coronavirus/physiology , Coronavirus/ultrastructure , Coronavirus Infections/pathology , Dendritic Cells/immunology , Humans , Immunity, Innate , Inflammation , Lung/immunology , Lung/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Receptors, Pattern Recognition/immunology , Receptors, Pattern Recognition/metabolism , T-Lymphocytes/immunology
8.
Virol Sin ; 2020 Sep 30.
Article in English | MEDLINE | ID: covidwho-807530

ABSTRACT

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) is the first pandemic caused by coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no effective anti-SARS-CoV-2 drug approved worldwide for treatment of patients with COVID-19. Therapeutic options in response to the COVID-19 outbreak are urgently needed. To facilitate the better and faster development of therapeutic COVID-19 drugs, we present an overview of the global promising therapeutic drugs, including repurposing existing antiviral agents, network-based pharmacology research, antibody development and traditional Chinese medicine. Among all these drugs, we focus on the most promising drugs (such as favipiravir, tocilizumab, SARS-CoV-2 convalescent plasma, hydroxychloroquine, Lianhua Qingwen, interferon beta-1a, remdesivir, etc.) that have or will enter the final stage of human testing-phase III-IV clinical trials.

9.
Preprint | SSRN | ID: ppcovidwho-709

ABSTRACT

Background: The outbreak of the 2019 novel coronavirus (2019-nCoV, also named SARS-CoV-2) has spread from Wuhan to outside of Hubeprovince and other countries

10.
Front Cell Infect Microbiol ; 10: 284, 2020.
Article in English | MEDLINE | ID: covidwho-613079

ABSTRACT

To investigate the early epidemic of COVID-19, a total of 176 confirmed COVID-19 cases in Shiyan city, Hubei province, China were surveyed. Our data indicated that the rate of emergence of early confirmed COVID-19 cases in Hubei province outside Wuhan was dependent on migration population, and the second-generation of patients were family clusters originating from Wuhan travelers. Epidemiological investigation indicated that the reproductive number (R0) under containment strategies was 1.81, and asymptomatic SARS-CoV-2 carriers were contagious with a transmission rate of 10.7%. Among the 176 patients, 53 were admitted to the Renmin Hospital of Hubei University of Medicine. The clinical characteristics of these 53 patients were collected and compared based on a positive RT-PCR test and presence of pneumonia. Clinical data showed that 47.2% (25/53) of COVID-19 patients were co-infected with Mycoplasma pneumoniae, and COVID-19 patients coinfected with M. pneumoniae had a higher percentage of monocytes (P < 0.0044) and a lower neutrophils percentage (P < 0.0264). Therefore, it is important to assess the transmissibility of infected asymptomatic individuals for SARS-CoV-2 transmission; moreover, clinicians should be alert to the high incidence of co-infection with M. pneumoniae in COVID-19 patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Asymptomatic Infections/epidemiology , Blood Cell Count , Carrier State/epidemiology , Child , Child, Preschool , China/epidemiology , Coinfection/epidemiology , Contact Tracing , Coronavirus Infections/complications , Coronavirus Infections/transmission , Female , Humans , Infant , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pneumonia, Mycoplasma/complications , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Tomography, X-Ray Computed , Travel , Young Adult
11.
Ann Transl Med ; 8(10): 623, 2020 May.
Article in English | MEDLINE | ID: covidwho-609905

ABSTRACT

Background: To clarify the characteristic and the duration of positive nucleic acid in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including asymptomatic children. Methods: A total of 32 children confirmed with SARS-CoV-2 infection between January 24 and February 12, 2020 from four provinces in western China were enrolled in this study and followed up until discharge and quarantine 14 days later. Results: Eleven children (34%) were asymptomatic, among whom six children had normal computed tomographic (CT) scan images. Age and gender were not associated with clinical symptoms or the results of CT scan in children infected with SARS-CoV-2. The concentrations of white blood cells and neutrophils were higher in children with asymptomatic infection than in children with clinical symptoms or CT abnormalities. Patients who presented with CT abnormalities had lower D-dimer or lower total bilirubin than those who had normal CT scan but clinical symptoms. All children recovered and no one died or was admitted to the pediatric intensive care unit (PICU). The mean duration of positive SARS-CoV-2 nucleic acid was 15.4 (SD =7.2) days and similar for both asymptomatic children and children with symptoms or CT abnormalities. We found a significant negative correlation between the lymphocyte count and the duration of positive nucleic acid test. Conclusions: Children with asymptomatic infection should be quarantined for the same duration as symptomatic patients infected with SARS-CoV-2. The clinical significance and mechanism behind the negative correlation between the number of lymphocytes and the duration of positive SARS-CoV-2 needs further study.

12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 2020.
Article | WHO COVID | ID: covidwho-238993

ABSTRACT

OBJECTIVE: To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid METHODS: Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method RESULTS: There was no symptoms and signs during the quarantine period in all 7 patients However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria CONCLUSIONS: There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary

14.
Travel Med Infect Dis ; 37: 101673, 2020.
Article in English | MEDLINE | ID: covidwho-71838

ABSTRACT

COVID-19 (corona virus disease 2019) is a kind of acute severe pneumonia caused by 2019-nCoV (2019-nCoV) infection. Since December 2019, it has been found in Wuhan, Hubei Province, and then spread to the whole country. Some parts of the world also showed an outbreak trend [1-3]. Real-time fluorescence quantitative reverse transcriptase polymerase chain reaction (reverse transcriptase-polymerase chain reaction,RT-PCR) and viral gene sequencing are the gold standard for the diagnosis of COVID-19. At present, upper respiratory tract nasopharyngeal swabs are mostly used as nucleic acid detection samples in China, but the positive rate is low. However, there are few reports on clinical application of 2019-nCoV nucleic acid detection in other biological samples. Methods: | The East Section of Renmin Hospital of Wuhan University is a designated COVID-19 hospital in Wuhan City, Hubei Province, China. This observation study included 132 patients diagnosed with COVID-19 in the infectious disease areas of the East Section of Renmin Hospital of Wuhan University from 2020.1.31 to 2020.2.29. COVID-19 diagnostic criteria: according to China's ⟪pneumonia diagnosis and treatment Program of novel coronavirus infection (trial version 7) ⟫, in accordance with the relevant epidemiological and clinical manifestations, nasopharyngeal swabs real-time fluorescence RT-PCR detection of 2019-nCoV nucleic acid positive, COVID-19 cases were divided into mild, ordinary, severe and severe [1]. The nasopharyngeal swabs of 132 cases of COVID-19 were positive for 2019-nCoV nucleic acid on admission, including 72 males and 60 females, with an average age of 66.7 ± 9.1 years, including 80 cases of common type, 44 cases of severe type and 8 cases of critical type. During the period of admission, under the condition of tertiary protection, nasopharyngeal swabs, sputum, blood, feces and anal swabs of COVID-19 cases were collected many times in the isolation ward for 2019-nCoV nucleic acid detection. All biological samples are sealed and transferred to the laboratory in strict accordance with the standard process. The RT-PCR test kits (BioGerm) were recommended by the Chinese Center for Disease Control and Prevention. The same technician and brand of test kit was used for all RT-PCR testing reported; both internal controls and negative controls were routinely performed with each batch of tests. Results: | 132 the results of 2019-nCoV nucleic acid test of various biological samples during the treatment of confirmed COVID-19 cases are as follows: the positive rate of 2019-nCoV nucleic acid test of nasopharyngeal swab is 38.13% (180/472 times), the positive rate of 2019-nCoV nucleic acid test of sputum is 48.68% (148/304 times), the positive rate of blood 2019-nCoV nucleic acid test is 3.03% (4/132 times), and the positive rate of 2019-nCoV nucleic acid test of feces is 9.83% (24/244 times). The positive rate of 2019-nCoV nucleic acid detection in anal swabs is 10.00% (12/120 times). Discussion|: In this study, it was found that the positive rate of 2019-nCoV nucleic acid in sputum of 132 patients with COVID-19 was higher than that of nasopharyngeal swabs, and viral nucleic acids were also detected in blood and digestive tract (fecal/anal swabs). Simple detection of nasopharyngeal swab 2019-nCoV nucleic acid detection positive rate is not high, multi-sample 2019-nCoV nucleic acid detection can improve the accuracy, reduce the false negative rate, better guide clinical treatment and evaluate the therapeutic effect.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Reverse Transcriptase Polymerase Chain Reaction/methods , Aged , Betacoronavirus/genetics , China/epidemiology , Coronavirus Infections/blood , Coronavirus Infections/virology , Feces/virology , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Sputum/virology
15.
Virology ; 546: 88-97, 2020 07.
Article in English | MEDLINE | ID: covidwho-71808

ABSTRACT

The emergence and re-emergence of Zika virus (ZIKV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas worldwide. Despite these burdens, antiviral therapies do not exist, and inhibitors of ZIKV are therefore urgently needed. To elucidate the anti-ZIKV effect of lycorine, we used reverse transcription-quantitative real-time PCR (qRT-PCR), immunofluorescence, Westernwestern blot, and plaque forming assay to analyse viral RNA (vRNA), viral protein, progeny virus counts, and validated inhibitors in vitro using a variety of cell lines. Additionally, we found that lycorine acts post-infection according to time-of-addition assay, and inhibits RdRp activity. Lycorine protected AG6 mice against ZIKV-induced lethality by decreasing the viral load in the blood. Due to its potency and ability to target ZIKV infection in vivo and in vitro, lycorine might offer promising therapeutic possibilities for combatting ZIKV infections in the future.


Subject(s)
Amaryllidaceae Alkaloids/administration & dosage , Antiviral Agents/administration & dosage , Phenanthridines/administration & dosage , Zika Virus Infection/drug therapy , Zika Virus/drug effects , Amaryllidaceae Alkaloids/chemistry , Animals , Antiviral Agents/chemistry , Female , Humans , Male , Mice , Molecular Docking Simulation , Phenanthridines/chemistry , Virus Replication/drug effects , Zika Virus/genetics , Zika Virus/physiology , Zika Virus Infection/mortality , Zika Virus Infection/virology
16.
J Med Virol ; 92(6): 595-601, 2020 06.
Article in English | MEDLINE | ID: covidwho-2181

ABSTRACT

From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID-19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID-19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS-CoV-2 is spreading among the public and causing substantial burden due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor-binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin-converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to humans.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Pandemics , Peptidyl-Dipeptidase A/chemistry , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Receptors, Virus/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Amino Acid Sequence , Animals , Betacoronavirus/classification , Betacoronavirus/pathogenicity , Binding Sites , China/epidemiology , Chiroptera/virology , Coronavirus Infections/virology , Eutheria/virology , Humans , Models, Molecular , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phylogeny , Pneumonia, Viral/virology , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Protein Interaction Mapping , Receptors, Virus/genetics , Receptors, Virus/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Snakes/virology , Spike Glycoprotein, Coronavirus/classification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Turtles/virology
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