Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
BMC Infect Dis ; 20(1): 647, 2020 Sep 03.
Article in English | MEDLINE | ID: covidwho-744977

ABSTRACT

BACKGROUND: The family cluster is one of most important modes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission throughout China, and more details are needed about how family clusters cause the spread of coronavirus disease 2019 (COVID-19). CASE PRESENTATION: We retrospectively reviewed 7 confirmed cases from one family cluster. Both clinical features and laboratory examination results were described. Patient 1 had been in close contact with someone who was later confirmed to have COVID-19 in Wuhan City before he returned back to his hometown. He had dinner with 6 other members in his family. All the persons developed COVID-19 successively except for one older woman who neither had dinner with them nor shared a sleeping room with her husband. Six patients had mild or moderate COVID-19 but one older man with underlying diseases progressed into the severe type. After general and symptomatic treatments, all the patients recovered. CONCLUSIONS: In a family cluster, having dinner together may be an important mode for the transmission of SARS-CoV-2. In this setting, most cases are mild with a favorable prognosis, while elderly patients with underlying diseases may progress into the severe type. For someone who has close contact with a confirmed case, 14-day isolation is necessary to contain virus transmission.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Family Health , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Adolescent , Adult , Aged , Betacoronavirus/pathogenicity , Child , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies
3.
Preprint | bioRxiv | ID: ppbiorxiv-267781

ABSTRACT

COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months and a global fight against both is still going on. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code, to molecular mechanisms based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on replicase-transcriptase complex. Our analysis starts with primary sequence information and identity-based phylogeny based on 22,051 SARS-CoV-2 genome sequences and evaluation of sequence variation patterns as mutation spectrum and its 12 permutations among organized clades tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings include: (1) The most dominant mutation is C-to-U permutation whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity albeit assumed most slightly deleterious. (2) The second abundance group includes: three negative-strand mutations U-to-C, A-to-G, G-to-A and a positive-strand mutation G-to-U generated through an identical mechanism as C-to-U. (3) A clade-associated and biased mutation trend is found attributable to elevated level of the negative-sense strand synthesis. (4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes. These findings demand a bioinformatics platform where emerging mutations are mapped on to mostly subtle but fast-adjusting viral proteomes and transcriptomes to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications. Such thoughts and actions are in desperate need, especially in the middle of the War against COVID-19.

5.
Nat Commun ; 11(1): 3910, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-697036

ABSTRACT

SARS-CoV-2, a ß-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Epithelial Cells/virology , Morphogenesis/physiology , Pneumonia, Viral/virology , Respiratory System/virology , Betacoronavirus/pathogenicity , Cell Line , Cells, Cultured , Cytopathogenic Effect, Viral , Epithelial Cells/pathology , Humans , Pandemics , Respiratory System/pathology , Tropism , Virus Replication
6.
Int. J. Ophthalmol. ; 7(13): 1161-1163, 20200718.
Article in English | ELSEVIER | ID: covidwho-657037
7.
Jpn J Radiol ; 2020 Jun 12.
Article in English | MEDLINE | ID: covidwho-594903

ABSTRACT

PURPOSE: To explore the dynamic changes and correlation between CT imaging manifestations and cellular immunity of COVID-19. MATERIALS AND METHODS: This retrospective review analyzed 23 patients with COVID-19, including 13 males and 10 females aged 27-70 years, with an average age of 48 years. Patients were divided into two groups: group A with 11 critical-severe patients, and group B with 12 common-mild patients. Clinical, laboratory, and radiological data were collected and analyzed. RESULTS: LYM, LYM (%), CD3+, CD4+, and CD8+ decreased, while NEU (%), CRP, and CT scores increased in all patients, WBC in group A increased. In group A, on day 10-12 after disease onset, CT scores and CRP reached the highest point, and day 13-15 LYM, LYM (%) reached the lowest but NEU (%) and WBC reached the highest, CD3+, CD4+ and CD8+ were at the lowest on day 10-15. In group B, on day 7-9, CT scores, NEU (%) and CRP reached the peak, but LYM, LYM (%), CD3+, CD4+ and CD8+ reached the lowest. In all patients, CT scores had a significantly negative correlation with CD3+, CD4+, CD8+, LYM (%), and LYM (p = 0.001, r = - 0.797; p = 0.008, r = - 0.698; p = 0.002, r = - 0.775; p < 0.001, r = - 0.785; p = 0.021, r = - 0.571, respectively), and a significantly positive correlation with WBC and NEU (%) (p < 0.001, r = 0.785; p = 0.003, r = 0.691, respectively). CONCLUSION: Dynamic changes of CT manifestations and cellular immunity of patients with COVID-19 were regular and correlation was high between these two parameters.

9.
Cell ; 182(3): 713-721.e9, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-549043

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Drug Evaluation, Preclinical/methods , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccines, Inactivated/therapeutic use , Viral Vaccines/therapeutic use , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/genetics , Chlorocebus aethiops , Coronavirus Infections/virology , Disease Models, Animal , Female , Guinea Pigs , Immunogenicity, Vaccine , Macaca fascicularis , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Phylogeny , Pneumonia, Viral/virology , Rabbits , Rats , Rats, Wistar , Vaccines, Inactivated/adverse effects , Vero Cells , Viral Vaccines/adverse effects
10.
Emerg Microbes Infect ; 9(1): 1123-1130, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-457402

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.


Subject(s)
Coronavirus Infections/diagnosis , Interleukin-10/blood , Interleukin-6/blood , Pneumonia, Viral/diagnosis , Betacoronavirus , Biomarkers/blood , C-Reactive Protein/analysis , China , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Critical Illness , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Cytokines/blood , Humans , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology
11.
Iran. J. Radiol. ; 2(17)20200401.
Article in English | ELSEVIER | ID: covidwho-309584

ABSTRACT

Coronavirus disease (COVID-19) broke out in Wuhan, China. It was a highly contagious respiratory disease, the basic reproductive number (RO value) for COVID-19 was reported to be 2.68 with an epidemic doubling time of 6.4 days. In this case report, a 50-yearold man presented with a history of fever and chills. Chest radiographs failed to find any abnormality, and computed tomography (CT) showed ground glass shadow of the upper lobe of the left lung. Real-time polymerase chain reaction (RT-PCR) of the patient’s pharyngeal swab was positive for COVID-19 nucleic acid. The course of the disease developed from mild to severe, then improved and recovered. The patient underwent antiviral drugs, low dose of glucocorticoids, symptomatic treatment, and immunoglobulin for human intravenous injection. We report this long time follow-up case of COVID-19.

13.
Nature ; 583(7818): 830-833, 2020 07.
Article in English | MEDLINE | ID: covidwho-220333

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Coronavirus Infections/virology , Lung/pathology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Transgenes , Animals , Antigens, Viral/immunology , Antigens, Viral/metabolism , Betacoronavirus/immunology , Betacoronavirus/metabolism , Bronchi/pathology , Bronchi/virology , Coronavirus Infections/immunology , Disease Models, Animal , Epithelial Cells/pathology , Epithelial Cells/virology , Female , Humans , Immunoglobulin G/immunology , Lung/immunology , Lung/virology , Lymphocytes/immunology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/virology , Male , Mice , Mice, Transgenic , Pandemics , Pneumonia, Viral/immunology , Receptors, Complement 3d/genetics , Receptors, Complement 3d/metabolism , Virus Replication , Weight Loss
14.
Preprint | medRxiv | ID: ppmedrxiv-20091413

ABSTRACT

Background: Since it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear. Methods: 3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis. Results: We detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D. Conclusions: We classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.

15.
Animal Models and Experimental Medicine ; n/a(n/a), 2020.
Article | WHO COVID | ID: covidwho-20861

ABSTRACT

Abstract Background Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models Methods Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response Results Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia Viral antigens were detected mainly in alveolar epithelial cells and macrophages Conclusion SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection

17.
Emerg Infect Dis ; 26(6): 1324-1326, 2020 06.
Article in English | MEDLINE | ID: covidwho-6800

ABSTRACT

We report co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus in a patient with pneumonia in China. The case highlights possible co-detection of known respiratory viruses. We noted low sensitivity of upper respiratory specimens for SARS-CoV-2, which could further complicate recognition of the full extent of disease.


Subject(s)
Coronavirus Infections/diagnosis , Influenza, Human/diagnosis , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus/isolation & purification , Bronchoalveolar Lavage Fluid/virology , China , Clinical Laboratory Techniques , Coinfection , Coronavirus Infections/virology , Humans , Influenza A virus , Influenza, Human/virology , Male , Nasopharynx/virology , Pandemics , Pneumonia, Viral/virology
18.
Clin Infect Dis ; 71(15): 732-739, 2020 07 28.
Article in English | MEDLINE | ID: covidwho-5562

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in 2019 and subsequently spread worldwide. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late phase in critically ill patients with SARS-CoV-2. Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection. METHODS: The pharmacological activity of chloroquine and hydroxychloroquine was tested using SARS-CoV-2-infected Vero cells. Physiologically based pharmacokinetic (PBPK) models were implemented for both drugs separately by integrating their in vitro data. Using the PBPK models, hydroxychloroquine concentrations in lung fluid were simulated under 5 different dosing regimens to explore the most effective regimen while considering the drug's safety profile. RESULTS: Hydroxychloroquine (EC50 = 0.72 µM) was found to be more potent than chloroquine (EC50 = 5.47 µM) in vitro. Based on PBPK models results, a loading dose of 400 mg twice daily of hydroxychloroquine sulfate given orally, followed by a maintenance dose of 200 mg given twice daily for 4 days is recommended for SARS-CoV-2 infection, as it reached 3 times the potency of chloroquine phosphate when given 500 mg twice daily 5 days in advance. CONCLUSIONS: Hydroxychloroquine was found to be more potent than chloroquine to inhibit SARS-CoV-2 in vitro.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Hydroxychloroquine/pharmacology , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Animals , Antiviral Agents/pharmacokinetics , Cell Line , Chlorocebus aethiops , Chloroquine/pharmacokinetics , Chloroquine/pharmacology , Hydroxychloroquine/pharmacokinetics , Lung/drug effects , Pandemics , Vero Cells
19.
Lancet ; 395(10224): 565-574, 2020 02 22.
Article in English | MEDLINE | ID: covidwho-80

ABSTRACT

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Genome, Viral , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Receptors, Virus/metabolism , Betacoronavirus/metabolism , Bronchoalveolar Lavage Fluid/virology , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , DNA, Viral/genetics , Disease Reservoirs/virology , Genomics/methods , High-Throughput Nucleotide Sequencing/methods , Humans , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Sequence Alignment
SELECTION OF CITATIONS
SEARCH DETAIL