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1.
EMBO Rep ; 2020.
Article | WHO COVID | ID: covidwho-662381

ABSTRACT

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3 USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications Notably, TGF-ß induces USP44 expression during iTreg differentiation USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3 Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy

2.
Protein Cell ; 2020 Sep 07.
Article in English | MEDLINE | ID: covidwho-746138
3.
Signal Transduct Target Ther ; 5(1): 157, 2020 10 19.
Article in English | MEDLINE | ID: covidwho-724972

ABSTRACT

Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Callithrix/virology , Coronavirus Infections/epidemiology , Disease Models, Animal , Macaca fascicularis/virology , Macaca mulatta/virology , Pandemics , Pneumonia, Viral/epidemiology , Animals , Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , Body Temperature , Body Weight , Callithrix/immunology , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokines/biosynthesis , Cytokines/classification , Cytokines/immunology , Disease Susceptibility , Female , Humans , Lung/diagnostic imaging , Lung/immunology , Lung/pathology , Lung/virology , Macaca fascicularis/immunology , Macaca mulatta/immunology , Male , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Species Specificity , Tomography, X-Ray Computed , Viral Load , Virus Replication
6.
PLoS Med ; 17(7): e1003195, 2020 07.
Article in English | MEDLINE | ID: covidwho-691282

ABSTRACT

BACKGROUND: As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women. METHODS AND FINDINGS: In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children's Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups. CONCLUSIONS: In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study).


Subject(s)
Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Pregnancy Complications, Infectious/virology , Adult , Betacoronavirus/isolation & purification , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/pathology , Retrospective Studies
8.
BMC Pregnancy Childbirth ; 20(1): 394, 2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-635727

ABSTRACT

BACKGROUND: Compared with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), Corona Virus Disease 2019(COVID-19) spread more rapidly and widely. The population was generally susceptible. However, reports on pregnant women infected with SARS-CoV-2 were very limited. By sharing the clinical characteristics, treatments and outcomes of 18 patients with COVID-19 during late pregnancy, we hope to provide some references for obstetric treatment and management. METHODS: A total of 18 patients with COVID-19 treated at Renmin Hospital of Wuhan University were collected. The epidemiological characteristics, clinical manifestations, laboratory tests, chest CT and pregnancy outcomes were performed for analysis. RESULTS: 1. 18 cases of late pregnancy infected with SARS-CoV-2 pneumonia were delivered at 35 + 5 weeks to 41 weeks. According to the clinical classification of COVID-19, 1 case was mild type, 16 cases were ordinary type, and 1 case was severe type. 2. According to imaging examinations: 15 (83%) cases showed unilateral or bilateral pneumonia, 2 (11%) cases had pulmonary infection with pleural effusion, and 1 (6%) case had no abnormal imaging changes. 8 (44%) cases were positive and 10 (56%) cases were negative for nasopharyngeal-swab tests of SARS-CoV-2. 3. Among the 18 newborns, there were 3 (17%) premature infants, 1 (6%) case of mild asphyxia, 5 (28%) cases of bacterial pneumonia, 1 (6%) case of gastrointestinal bleeding, 1 (6%) case of necrotizing enteritis, 2 (11%) cases of hyperbilirubinemia and 1 (6%) case of diarrhea. All the newborns were negative for the first throat swab test of SARS-CoV-2 after birth. 4. Follow-up to Mar 7, 2020, no maternal and neonatal deaths occurred. CONCLUSIONS: The majority of patients in late term pregnancy with COVID-19 were of ordinary type, and they were less likely to develop into critical pneumonia after early isolation and antiviral treatment. Vertical transmission of SARS-CoV-2 was not detected, but the proportion of neonatal bacterial pneumonia was higher than other neonatal diseases in newborns.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Infectious Disease Transmission, Vertical/statistics & numerical data , Pneumonia, Viral/complications , Pregnancy Complications, Infectious/virology , Adult , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Infant, Newborn , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Premature Birth/epidemiology , Premature Birth/virology
9.
Cancer Discov ; 10(6): 783-791, 2020 06.
Article in English | MEDLINE | ID: covidwho-631598

ABSTRACT

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. SIGNIFICANCE: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients.This article is highlighted in the In This Issue feature, p. 747.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Neoplasms , Pneumonia, Viral/therapy , Aged , China/epidemiology , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Disease Outbreaks , Female , Humans , Intensive Care Units , Male , Middle Aged , Neoplasms/complications , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Respiration, Artificial
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.
Dermatol Ther ; : e13831, 2020 Jun 15.
Article in English | MEDLINE | ID: covidwho-598791
13.
Rev Soc Bras Med Trop ; 53: e20200227, 2020.
Article in English | MEDLINE | ID: covidwho-520055

ABSTRACT

The novel coronavirus pneumonia (NCP) outbreak occurred in Wuhan, China at the end of 2019. Here, we report the clinical characteristics and therapeutic procedure for a case of severe NCP. The patient was started on glucocorticoids and non-invasive ventilator treatment. After treatment, the patient's symptoms improved, and the status was confirmed as NCP negative. Our results may provide clues for the treatment of NCP.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Glucocorticoids/administration & dosage , Pneumonia, Viral/therapy , Combined Modality Therapy , Coronavirus Infections/diagnostic imaging , Female , Humans , Middle Aged , Noninvasive Ventilation , Pandemics , Pneumonia, Viral/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome
14.
Int J Environ Res Public Health ; 17(11)2020 05 26.
Article in English | MEDLINE | ID: covidwho-378222

ABSTRACT

BACKGROUND: COVID-19 has become one of the most serious global epidemics in the 21st Century. This study aims to explore the distribution of research capabilities of countries, institutions, and researchers, and the hotspots and frontiers of coronavirus research in the past two decades. In it, references for funding support of urgent projects and international cooperation among research institutions are provided. METHOD: the Web of Science core collection database was used to retrieve the documents related to coronavirus published from 2003 to 2020. Citespace.5.6.R2, VOSviewer1.6.12, and Excel 2016 were used for bibliometric analysis. RESULTS: 11,036 documents were retrieved, of which China and the United States have contributed the most coronavirus studies, Hong Kong University being the top contributor. Regarding journals, the Journal of Virology has contributed the most, while in terms of researchers, Yuen Kwok Yung has made the most contributions. The proportion of documents published by international cooperation has been rising for decades. Vaccines for SARS-CoV-2 are under development, and clinical trials of several drugs are ongoing. CONCLUSIONS: international cooperation is an important way to accelerate research progress and achieve success. Developing corresponding vaccines and drugs are the current hotspots and research directions.


Subject(s)
Bibliometrics , Biomedical Research/statistics & numerical data , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Publications/statistics & numerical data , Betacoronavirus , Databases, Factual , Humans , Pandemics
15.
Chin. Trad. Herbal Drugs ; 7(51): 1677-1684, 20200412.
Article in Chinese | ELSEVIER | ID: covidwho-379404

ABSTRACT

Objective: To investigate the multi compound-target-pathway mechanism of Renshen Baidu Powder (RSBDS) in the treatment of COVID-19 from cytokine perspective. Methods: The active compounds of RSBDS were collected by TCMSP and the cytokine storm related targets were collected by the drug target database. The interaction network of RSBDS on single drug-active compounds-targets was established by Cytoscape. The interaction network, GO function and KEGG pathway of the targets were analyzed by String and DAVID databases. Results: The interaction network of RSBDS on single drug-active compounds-targets included 10 kinds of medicinal materials, 211 active compounds and 151 disease targets. Interaction network showed that the targets related to the inhibition to cytokine storm of RSBDS on COVID-19 might include STAT3, MAPK1, NFκB1, PIK3CA, MAPK3, TNF, CXCR4, VEGFA, IL-6, IL-2, etc. GO function showed that above targets in biological function involved chemotaxis and steroid metabolism; Molecular function entries involved heme binding, iron ion binding and oxygen binding; Cell composition entries involved cell surface and cell membrane. KEGG pathway showed that above targets participated in the regulation of Chagas disease, HIF-1 signaling pathway, TNF signaling pathway, etc. Conclusion: The multi compound-target-pathways effect of RSBDS on COVID-19 was realized by inhibiting cytokine storm, which through regulating chemotaxis, increasing blood oxygen saturation, inhibiting STAT, MAPK, NFκB, PIK3K and IL-6 signal pathways.

18.
Ann. Transl. Med. ; 7(8)20200401.
Article in English | ELSEVIER | ID: covidwho-258164

ABSTRACT

Novel coronavirus (2019-nCov) infection (COVID-19) rapidly spread across China and 25 countries in the worldwide, which infected not only adults but also children, even neonates. Each year, about 15 million newborns are delivered in China. Newborn screening (NBS) helps effectively prevent some mental retardation, premature death, and adverse outcomes in the early stage of baby, which could detect some inherited metabolic disorders (IMDs). During this COVID-19 epidemic, how to balance the risk of infected 2019-nCov and the risk of disability and teratogenesis of IMDs. Expert members of NBS extra quality assessment in National Clinical Center of Laboratory (NCCL) give a brief consensus for NBS of IMDs in the COVID-2019 epidemic, hoping that the brief consensus could be reference for NBS of IMDs in the other epidemic areas or periods all over the world.

19.
Clin Infect Dis ; 2020 May 11.
Article in English | MEDLINE | ID: covidwho-235997
20.
Curr Biol ; 30(11): 2196-2203.e3, 2020 06 08.
Article in English | MEDLINE | ID: covidwho-232567

ABSTRACT

The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1, 2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomic analysis of samples from 227 bats collected from Yunnan Province in China between May and October 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Chiroptera/virology , Mutagenesis, Insertional , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Animals , Betacoronavirus/chemistry , Eutheria/virology , Feces/virology , Genome, Viral , Models, Molecular , Phylogeny , RNA, Viral/genetics , SARS Virus/genetics , Sequence Alignment , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/chemistry
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