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1.
Pediatr Dermatol ; 37(3): 435-436, 2020 May.
Article in English | MEDLINE | ID: covidwho-2097853

ABSTRACT

It has been reported that the novel coronavirus disease (COVID-19) may be associated with a papulovesicular skin eruption predominantly involving the trunk. We hereby present a case of COVID-19-associated varicella-like exanthem in an 8-year-old girl with mild systemic symptoms.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/pathology , Exanthema/diagnosis , Exanthema/virology , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , COVID-19 , Child , Female , Humans , Pandemics , SARS-CoV-2
3.
Virology ; 575: 1-9, 2022 10.
Article in English | MEDLINE | ID: covidwho-1984217

ABSTRACT

Coronavirus infection of cells differentially regulates the expression of host genes and their related pathways. In this study, we present the transcriptomic profile of cells infected with gammacoronavirus infectious bronchitis virus (IBV). In IBV-infected human non-small cell lung carcinoma cells (H1299 cells), a total of 1162 differentially expressed genes (DEGs), including 984 upregulated and 178 downregulated genes, was identified. These DEGs were mainly enriched in MAPK and Wnt signaling pathways, and 5 out of the 10 top upregulated genes in all transcripts were immediate-early response genes (IEGs). In addition, the induction of 11 transcripts was validated in IBV-infected H1299 and Vero cells by RT-qPCR. The accuracy, reliability and genericity of the transcriptomic data were demonstrated by functional characterization of these IEGs in cells infected with different coronaviruses in our previous publications. This study provides a reliable transcriptomic profile of host genes and pathways regulated by coronavirus infection.


Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Animals , Chickens/genetics , Chlorocebus aethiops , Coronavirus Infections/pathology , Humans , Infectious bronchitis virus/physiology , Reproducibility of Results , Signal Transduction , Transcriptome , Vero Cells
5.
Viruses ; 14(6)2022 06 06.
Article in English | MEDLINE | ID: covidwho-1911617

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae that causes severe diarrhea and high mortality in neonatal suckling piglets. Currently, there is no effective medication against this pathogen. Cepharanthine (CEP), tetrandrine (TET), and fangchinoline (FAN) are natural bis-benzylisoquinoline alkaloids with anti-inflammatory, antitumor, and antiviral properties. Here, we first found that CEP, TET, and FAN had anti-PEDV activity with IC50 values of 2.53, 3.50, and 6.69 µM, respectively. The compounds could block all the processes of viral cycles, but early application of the compounds before or during virus infection was advantageous over application at a late stage of virus replication. FAN performed inhibitory function more efficiently through interfering with the virus entry and attachment processes or through attenuating the virus directly. CEP had a more notable effect on virus entry. With the highest SI index of 11.8 among the three compounds, CEP was chosen to carry out animal experiments. CEP in a safe dosage of 11.1 mg/kg of body weight could reduce viral load and pathological change of piglet intestinal tracts caused by PEDV field strain challenge, indicating that CEP efficiently inhibited PEDV infection in vivo. All of these results demonstrated that the compounds of bis-benzylisoquinoline alkaloids could inhibit PEDV proliferation efficiently and had the potential of being developed for PED prevention and treatment.


Subject(s)
Benzylisoquinolines , Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Benzylisoquinolines/pharmacology , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Coronavirus Infections/veterinary , Diarrhea , Swine , Swine Diseases/pathology
6.
PLoS Pathog ; 18(6): e1010667, 2022 06.
Article in English | MEDLINE | ID: covidwho-1910704

ABSTRACT

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.


Subject(s)
Betacoronavirus 1 , COVID-19 , Coronavirus Infections/pathology , Olfaction Disorders , Animals , Betacoronavirus 1/physiology , Humans , Mice , Olfaction Disorders/virology , SARS-CoV-2 , Smell , Swine
7.
Nat Med ; 26(6): 842-844, 2020 06.
Article in English | MEDLINE | ID: covidwho-1900503

ABSTRACT

Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8+ T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Single-Cell Analysis , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2
8.
Avian Pathol ; 51(4): 339-348, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1830476

ABSTRACT

Infectious bronchitis is an acute and highly contagious disease caused by avian infectious bronchitis virus (IBV). As well as the typical clinical respiratory signs, such as dyspnoea and tracheal rales, QX genotype strains can also cause damage to the urinary system and reproductive system. Our previous studies found that chickens infected with QX-type IBV also displayed damage to the bursa of Fabricius. To investigate the effects of different genotypes of IBV on the bursa of Fabricius, we challenged one-week-old SPF chickens with Mass, QX and TW genotype IBV strains and compared the clinical signs, gross lesions, histopathological damage, viral loads, and expression levels of inflammatory cytokines (IL-6, IL-8, IL-1ß, IFN-α,ß, γ and TNF-α). The results showed that all three strains caused tissue damage, while significant temporal variations in the viral loads of the different infected groups were detected. IBV infection seriously interfered with the natural immune response mediated by inflammatory cytokines (IFN-α, IFN-ß, IL-6 and IFN-γ) in chickens. Our results suggested that IBV has potential immunological implications for chickens that may lead to poor production efficiency. RESEARCH HIGHLIGHTSAvian coronavirus IBV is an important pathogen of chickens.IBV has potential immunological implications in chickens.The bursal viral load of different IBV strains varies significantly.


Subject(s)
Bursa of Fabricius , Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Animals , Bursa of Fabricius/pathology , Bursa of Fabricius/virology , Chickens , Coronavirus Infections/pathology , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Cytokines/metabolism , Infectious bronchitis virus/classification , Infectious bronchitis virus/genetics , Infectious bronchitis virus/pathogenicity , Interleukin-6 , Poultry Diseases/pathology , Poultry Diseases/virology
9.
Nat Rev Immunol ; 20(7): 442-447, 2020 07.
Article in English | MEDLINE | ID: covidwho-1830064

ABSTRACT

A male bias in mortality has emerged in the COVID-19 pandemic, which is consistent with the pathogenesis of other viral infections. Biological sex differences may manifest themselves in susceptibility to infection, early pathogenesis, innate viral control, adaptive immune responses or the balance of inflammation and tissue repair in the resolution of infection. We discuss available sex-disaggregated epidemiological data from the COVID-19 pandemic, introduce sex-differential features of immunity and highlight potential sex differences underlying COVID-19 severity. We propose that sex differences in immunopathogenesis will inform mechanisms of COVID-19, identify points for therapeutic intervention and improve vaccine design and increase vaccine efficacy.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adaptive Immunity , Age Factors , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Female , Humans , Interferons/immunology , Male , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Sociological Factors
10.
Front Cell Infect Microbiol ; 12: 845368, 2022.
Article in English | MEDLINE | ID: covidwho-1793038

ABSTRACT

Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases.


Subject(s)
Coronavirus Infections , Coronavirus , Autophagy/physiology , Coronavirus/physiology , Coronavirus Infections/pathology , Humans , Inflammation , Viral Load , Virus Replication/physiology
11.
Vet Microbiol ; 267: 109391, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1778497

ABSTRACT

Protein tyrosine phosphatase non-receptor type 14 (PTPN14) is a member of the protein tyrosine phosphatase (PTP) family which is a potential tumor suppressor. PTPs modulate the cellular level of tyrosine phosphorylation under normal and pathological conditions. Porcine epidemic diarrhea virus (PEDV) is one of the most important pathogens in the swine industry. Our previous membrane proteomics results showed that PTPN14 was markedly upregulated in PEDV-infected Vero cells. However, its biological roles in PEDV infection have not yet been investigated. In this study, we reported PTPN14 functions as a novel regulator of signal transducer and activator of transcription 3 (STAT3) phosphorylation during PEDV infection. Firstly, PTPN14 was markedly upregulated in PEDV-infected Vero cells with the decrease of STAT3 phosphorylation. Knockdown of PTPN14 or phosphatase inhibitor treatment promoted PEDV proliferation and increased the phosphorylation of STAT3 in Vero cells. On the contrary, overexpression of PTPN14 inhibits viral infection in Vero cells. Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus. Collectively, our results indicate that PTPN14 plays a negative role in regulating STAT3 activation in PEDV infected Vero cells and demonstrate another layer of regulation in PEDV infection.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Animals , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/veterinary , Porcine epidemic diarrhea virus/physiology , Protein Tyrosine Phosphatases/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Swine , Tyrosine/metabolism , Vero Cells
13.
Travel Med Infect Dis ; 34: 101623, 2020.
Article in English | MEDLINE | ID: covidwho-1764000

ABSTRACT

INTRODUCTION: An epidemic of Coronavirus Disease 2019 (COVID-19) began in December 2019 in China leading to a Public Health Emergency of International Concern (PHEIC). Clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews on COVID-19 have been published to date. METHODS: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies and also case reports, were included, and analyzed separately. We performed a random-effects model meta-analysis to calculate pooled prevalences and 95% confidence intervals (95%CI). RESULTS: 660 articles were retrieved for the time frame (1/1/2020-2/23/2020). After screening, 27 articles were selected for full-text assessment, 19 being finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 95%CI 40.8-74.4%) and dyspnea (45.6%, 95%CI 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), 32.8% presented with acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock. Some 13.9% (95%CI 6.2-21.5%) of hospitalized patients had fatal outcomes (case fatality rate, CFR). CONCLUSION: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and hospitalization was associated with a CFR of >13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure and facilities to treat severe COVID-19.


Subject(s)
Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Betacoronavirus , COVID-19 , Coronavirus Infections/pathology , Cough/virology , Fever/virology , Hospitalization , Humans , Intensive Care Units , Pandemics , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/virology , SARS-CoV-2
15.
Analyst ; 145(12): 4173-4180, 2020 Jun 21.
Article in English | MEDLINE | ID: covidwho-1721601

ABSTRACT

Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.


Subject(s)
Circulating MicroRNA/blood , Fluorescent Dyes/chemistry , Spectrum Analysis, Raman , Urinary Bladder Neoplasms/diagnosis , Betacoronavirus/isolation & purification , Biomarkers, Tumor/blood , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Coronavirus Infections/virology , Gold/chemistry , Humans , Limit of Detection , Microscopy, Confocal , Nanostructures/chemistry , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Point-of-Care Systems , SARS-CoV-2 , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
16.
Cell Host Microbe ; 27(6): 879-882.e2, 2020 06 10.
Article in English | MEDLINE | ID: covidwho-1719463

ABSTRACT

The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.


Subject(s)
Coronavirus Infections/genetics , Coronavirus Infections/immunology , Pneumonia, Viral/genetics , Pneumonia, Viral/immunology , Adult , Aged , Biological Variation, Individual , COVID-19 , Cluster Analysis , Coronavirus Infections/blood , Coronavirus Infections/pathology , Cytokines/blood , Gene Expression Regulation , Humans , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Transcriptome , Up-Regulation
18.
J Altern Complement Med ; 26(6): 444-448, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1637539

ABSTRACT

Editor's Note: For those whose response to COVID-19 includes exploring beyond vaccines, conventional pharmaceuticals, and the watchful or healthy waiting until such tools might arrive, interest in cannabinoids has been high - and controversial. It has already stimulated one journal, the Liebert Cannabis and Cannabinoid Research, to issue a call for papers on COVID-19. The unique place of cannabis in the culture seems to always mark the herb with an exponential asterisk whenever basketed with the other natural health strategies that are both widely used, and as broadly derided. In this invited commentary, JACM Editorial Board member Michelle Sexton, ND starts by describing the multiple immune modulating effects associated with the herb. The University of California San Diego Assistant Adjunct Professor in Anesthesiology then asks: "Given these effects, can phytocannabinoids be either helpful, or harmful for immune competency, in the context of the current COVID-19 pandemic?" A skilled edge-walker, Sexton lets the research fall where it may in wending a path through this evidentiary maze. -John Weeks, Editor-in-Chief, JACM.


Subject(s)
Betacoronavirus/drug effects , Cannabinoids/therapeutic use , Coronavirus Infections/complications , Coronavirus Infections/pathology , Coronavirus/drug effects , Immunocompetence/drug effects , Medical Marijuana/pharmacology , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , COVID-19 , Female , Humans , Immunocompromised Host , Male , Middle Aged , Pandemics , SARS-CoV-2
19.
Emerg Microbes Infect ; 11(1): 168-171, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1623181

ABSTRACT

HCoV-OC43 is one of the mildly pathogenic coronaviruses with high infection rates in common population. Here, 43 HCoV-OC43 related cases with pneumonia were reported, corresponding genomes of HCoV-OC43 were obtained. Phylogenetic analyses based on complete genome, orf1ab and spike genes revealed that two novel genotypes of HCoV-OC43 have emerged in China. Obvious recombinant events also can be detected in the analysis of the evolutionary dynamics of novel HCoV-OC43 genotypes. Estimated divergence time analysis indicated that the two novel genotypes had apparently independent evolutionary routes. Efforts should be conducted for further investigation of genomic diversity and evolution analysis of mildly pathogenic coronaviruses.


Subject(s)
Common Cold/epidemiology , Coronavirus Infections/epidemiology , Coronavirus OC43, Human/genetics , Genome, Viral , Genotype , Pneumonia, Viral/epidemiology , Base Sequence , Bayes Theorem , Child , Child, Hospitalized , Child, Preschool , China/epidemiology , Common Cold/pathology , Common Cold/transmission , Common Cold/virology , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Coronavirus OC43, Human/classification , Coronavirus OC43, Human/pathogenicity , Epidemiological Monitoring , Female , Humans , Infant , Male , Monte Carlo Method , Mutation , Phylogeny , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Recombination, Genetic
20.
Clin Hemorheol Microcirc ; 75(1): 7-11, 2020.
Article in English | MEDLINE | ID: covidwho-1581406

ABSTRACT

There is growing evidence that COVID-19 not only affects the lungs but beyond that the endothelial system. Recent studies showed that this can lead to microcirculatory impairments and in consequence to functional disorders of all inner organs. The combination of endothelial dysfunction with a generalized inflammatory state and complement elements may together contribute to the overall pro-coagulative state described in COVID-19 patients leading to venular as well as to arteriolar occlusions.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Endothelium, Vascular/virology , Pneumonia, Viral/pathology , COVID-19 , Coronavirus Infections/virology , Endothelium, Vascular/pathology , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2
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