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1.
Sci Rep ; 11(1): 21259, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493217

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.


Subject(s)
COVID-19/complications , Orthomyxoviridae Infections/complications , Pneumonia, Viral/complications , SARS-CoV-2 , Animals , COVID-19/pathology , COVID-19/virology , Coinfection/pathology , Disease Models, Animal , Female , Humans , Interleukin-6/blood , Lung/diagnostic imaging , Lung/pathology , Mesocricetus , Orthomyxoviridae/pathogenicity , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Severity of Illness Index , Virus Replication
2.
EBioMedicine ; 71: 103546, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363149

ABSTRACT

BACKGROUND: Respiratory virus infections are significant causes of morbidity and mortality, and may induce host metabolite alterations by infecting respiratory epithelial cells. We investigated the use of liquid chromatography quadrupole time-of-flight mass spectrometry (LC/Q-TOF) combined with machine learning for the diagnosis of influenza infection. METHODS: We analyzed nasopharyngeal swab samples by LC/Q-TOF to identify distinct metabolic signatures for diagnosis of acute illness. Machine learning models were performed for classification, followed by Shapley additive explanation (SHAP) analysis to analyze feature importance and for biomarker discovery. FINDINGS: A total of 236 samples were tested in the discovery phase by LC/Q-TOF, including 118 positive samples (40 influenza A 2009 H1N1, 39 influenza H3 and 39 influenza B) as well as 118 age and sex-matched negative controls with acute respiratory illness. Analysis showed an area under the receiver operating characteristic curve (AUC) of 1.00 (95% confidence interval [95% CI] 0.99, 1.00), sensitivity of 1.00 (95% CI 0.86, 1.00) and specificity of 0.96 (95% CI 0.81, 0.99). The metabolite most strongly associated with differential classification was pyroglutamic acid. Independent validation of a biomarker signature based on the top 20 differentiating ion features was performed in a prospective cohort of 96 symptomatic individuals including 48 positive samples (24 influenza A 2009 H1N1, 5 influenza H3 and 19 influenza B) and 48 negative samples. Testing performed using a clinically-applicable targeted approach, liquid chromatography triple quadrupole mass spectrometry, showed an AUC of 1.00 (95% CI 0.998, 1.00), sensitivity of 0.94 (95% CI 0.83, 0.98), and specificity of 1.00 (95% CI 0.93, 1.00). Limitations include lack of sample suitability assessment, and need to validate these findings in additional patient populations. INTERPRETATION: This metabolomic approach has potential for diagnostic applications in infectious diseases testing, including other respiratory viruses, and may eventually be adapted for point-of-care testing. FUNDING: None.


Subject(s)
Influenza, Human/diagnosis , Machine Learning , Metabolome , Molecular Diagnostic Techniques/methods , Adolescent , Adult , Child , Child, Preschool , Female , Gas Chromatography-Mass Spectrometry/methods , Humans , Influenza, Human/metabolism , Influenza, Human/virology , Male , Metabolomics/methods , Nasal Mucosa/metabolism , Nasal Mucosa/virology , Orthomyxoviridae/pathogenicity , Pyrrolidonecarboxylic Acid/analysis
3.
Cell Mol Life Sci ; 78(21-22): 6735-6744, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1377320

ABSTRACT

Kallikrein-related peptidases (KLKs) or kallikreins have been linked to diverse (patho) physiological processes, such as the epidermal desquamation and inflammation, seminal clot liquefaction, neurodegeneration, and cancer. Recent mounting evidence suggests that KLKs also represent important regulators of viral infections. It is well-established that certain enveloped viruses, including influenza and coronaviruses, require proteolytic processing of their hemagglutinin or spike proteins, respectively, to infect host cells. Similarly, the capsid protein of the non-enveloped papillomavirus L1 should be proteolytically cleaved for viral uncoating. Consequently, extracellular or membrane-bound proteases of the host cells are instrumental for viral infections and represent potential targets for drug development. Here, we summarize how extracellular proteolysis mediated by the kallikreins is implicated in the process of influenza (and potentially coronavirus and papillomavirus) entry into host cells. Besides direct proteolytic activation of viruses, KLK5 and 12 promote viral entry indirectly through proteolytic cascade events, like the activation of thrombolytic enzymes that also can process hemagglutinin, while additional functions of KLKs in infection cannot be excluded. In the light of recent evidence, KLKs represent potential host targets for the development of new antivirals. Humanized animal models to validate their key functions in viral infections will be valuable.


Subject(s)
COVID-19/enzymology , COVID-19/virology , Host Microbial Interactions/physiology , Kallikreins/metabolism , SARS-CoV-2 , Virus Diseases/enzymology , Animals , Asthma/etiology , Coronavirus/genetics , Coronavirus/pathogenicity , Coronavirus/physiology , Host Microbial Interactions/genetics , Humans , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Papillomavirus Infections/enzymology , Papillomavirus Infections/virology , Picornaviridae Infections/complications , Picornaviridae Infections/enzymology , Picornaviridae Infections/virology , Protein Processing, Post-Translational , Proteolysis , Rhinovirus/pathogenicity , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Varicella Zoster Virus Infection/enzymology , Varicella Zoster Virus Infection/virology , Viral Proteins/genetics , Viral Proteins/metabolism , Virus Diseases/virology , Virus Internalization
4.
Front Immunol ; 11: 575074, 2020.
Article in English | MEDLINE | ID: covidwho-1256374

ABSTRACT

Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK-STAT signaling pathway activity assays to quantitatively measure the cellular immune response on Affymetrix expression microarray data of various types of blood samples from virally infected patients (influenza, RSV, dengue, yellow fever, rotavirus) or vaccinated individuals, and to determine vaccine immunogenicity. JAK-STAT1/2 pathway activity was increased in blood samples of patients with viral, but not bacterial, infection and was higher in influenza compared to RSV-infected patients, reflecting known differences in immunogenicity. High JAK-STAT3 pathway activity was associated with more severe RSV infection. In contrast to inactivated influenza virus vaccine, live yellow fever vaccine did induce JAK-STAT1/2 pathway activity in blood samples, indicating superior immunogenicity. Normal (healthy) JAK-STAT1/2 pathway activity was established, enabling assay interpretation without the need for a reference sample. The JAK-STAT pathway assays enable measurement of cellular immune response for prognosis, therapy stratification, vaccine development, and clinical testing.


Subject(s)
Dengue Virus/immunology , Immunity, Cellular , Orthomyxoviridae/immunology , Respiratory Syncytial Virus, Human/immunology , Rotavirus/immunology , Viral Vaccines/therapeutic use , Virus Diseases/immunology , Yellow fever virus/immunology , Biomarkers/blood , Dengue/blood , Dengue/immunology , Dengue/prevention & control , Dengue/virology , Dengue Vaccines/therapeutic use , Dengue Virus/pathogenicity , Diagnosis, Differential , Host-Pathogen Interactions , Humans , Immunogenicity, Vaccine , Influenza Vaccines/therapeutic use , Influenza, Human/blood , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Oligonucleotide Array Sequence Analysis , Orthomyxoviridae/pathogenicity , Predictive Value of Tests , RNA, Messenger/blood , RNA, Messenger/genetics , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/pathogenicity , Rotavirus/pathogenicity , Rotavirus Infections/blood , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Rotavirus Vaccines , Signal Transduction/genetics , Virus Diseases/blood , Virus Diseases/prevention & control , Virus Diseases/virology , Yellow Fever/blood , Yellow Fever/immunology , Yellow Fever/prevention & control , Yellow Fever/virology , Yellow Fever Vaccine/therapeutic use , Yellow fever virus/pathogenicity
5.
Nat Commun ; 12(1): 3249, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249208

ABSTRACT

Coronavirus disease 2019 (COVID-19) was detected in China during the 2019-2020 seasonal influenza epidemic. Non-pharmaceutical interventions (NPIs) and behavioral changes to mitigate COVID-19 could have affected transmission dynamics of influenza and other respiratory diseases. By comparing 2019-2020 seasonal influenza activity through March 29, 2020 with the 2011-2019 seasons, we found that COVID-19 outbreaks and related NPIs may have reduced influenza in Southern and Northern China and the United States by 79.2% (lower and upper bounds: 48.8%-87.2%), 79.4% (44.9%-87.4%) and 67.2% (11.5%-80.5%). Decreases in influenza virus infection were also associated with the timing of NPIs. Without COVID-19 NPIs, influenza activity in China and the United States would likely have remained high during the 2019-2020 season. Our findings provide evidence that NPIs can partially mitigate seasonal and, potentially, pandemic influenza.


Subject(s)
COVID-19/epidemiology , Influenza, Human/epidemiology , Models, Statistical , Pandemics , Respiratory Tract Infections/epidemiology , COVID-19/transmission , COVID-19/virology , China/epidemiology , Humans , Influenza, Human/transmission , Influenza, Human/virology , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Personal Protective Equipment , Physical Distancing , Quarantine/organization & administration , Respiratory Tract Infections/transmission , Respiratory Tract Infections/virology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Seasons , United States/epidemiology
6.
Epidemiol Infect ; 149: e96, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1182771

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.


Subject(s)
COVID-19/transmission , SARS-CoV-2/pathogenicity , Viral Load , Adenoviridae/pathogenicity , Animals , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Communicable Disease Control , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cricetinae , Enterovirus/pathogenicity , Ferrets , Humans , Macaca mulatta , Mice , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Orthomyxoviridae/pathogenicity , Respiratory Syncytial Viruses/pathogenicity , Rhinovirus/pathogenicity , SARS Virus/pathogenicity , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology , Virus Diseases/epidemiology , Virus Diseases/transmission , Virus Diseases/virology
7.
Life Sci Alliance ; 4(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1170604

ABSTRACT

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.


Subject(s)
Influenza in Birds/virology , Membrane Proteins/chemistry , Orthomyxoviridae/pathogenicity , Serine Endopeptidases/chemistry , Animals , Birds , Crystallography, X-Ray , Humans , Protein Conformation
8.
J Basic Clin Physiol Pharmacol ; 32(3): 131-143, 2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1088787

ABSTRACT

Coronavirus COVID-19 pandemic invades the world. Public health evaluates the incidence of infections and death, which should be reduced and need desperately quarantines for infected individuals. This article review refers to the roles of Ginkgo Biloba to reduce the risk of infection in the respiratory tract, the details on the epidemiology of corona COVID-19 and influenza, and it highlights how the Ginko Biloba could have been used as a novel treatment.Ginkgo Biloba can reduce the risk of infection by several mechanisms; these mechanisms involve Ginkgo Biloba contains quercetin and other constituents, which have anti-inflammatory and immune modulator effects by reducing pro-inflammatory cytokines concentrations. Cytokines cause inflammation which have been induced the injuries in lung lining.Some observational studies confirmed that Ginkgo Biloba reduced the risk of asthma, sepsis and another respiratory disease as well as it reduced the risk of cigarette smoking on respiratory symptoms. While other evidences suggested the characters of Ginkgo Biloba as an antivirus agent through several mechanisms. Ginkgolic acid (GA) can inhibit the fusion and synthesis of viral proteins, thus, it inhibit the Herpes Simplex Virus type1 (HSV-1), genome replication in Human Cytomegalovirus (HCMV) and the infections of the Zika Virus (ZIKV). Also, it inhibits the wide spectrum of fusion by inhibiting the three types of proteins that have been induced fusion as (Influenza A Virus [IAV], Epstein Barr Virus [EBV], HIV and Ebola Virus [EBOV]).The secondary mechanism of GA targeting inhibition of the DNA and protein synthesis in virus, greatly have been related to its strong effects, even afterward the beginning of the infection, therefore, it potentially treats the acute viral contaminations like (Measles and Coronavirus COVID-19). Additionally, it has been used topically as an effective agent on vigorous lesions including (varicella-zoster virus [VZV], HSV-1 and HSV-2). Ginkgo Biloba may be useful for treating the infected people with coronavirus COVID-19 through its beneficial effect. To assess those recommendations should be conducted with random control trials and extensive population studies.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Influenza, Human/drug therapy , Orthomyxoviridae/drug effects , Plant Extracts/therapeutic use , SARS-CoV-2/drug effects , Antiviral Agents/adverse effects , COVID-19/epidemiology , COVID-19/virology , Ginkgo biloba , Host-Pathogen Interactions , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Orthomyxoviridae/pathogenicity , Plant Extracts/adverse effects , SARS-CoV-2/pathogenicity , Treatment Outcome
9.
Infect Dis (Lond) ; 53(2): 111-121, 2021 02.
Article in English | MEDLINE | ID: covidwho-1066203

ABSTRACT

BACKGROUND: We compared the clinical characteristics, findings, and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. METHODS: From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at a tertiary care hospital in Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for 3 months from admission. RESULTS: We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs. 67%) and had at least one comorbidity (68% vs. 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs. 15 [45%], p=.03 and 1 [4%] vs. 10 [30%], p=.008). In chest X-ray at admission, ground-glass opacities (GGOs) and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], p<.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs. 19 [58%], p=.003 and 8 [29%] vs. 2 [6%], p=.034). COVID-19 patients were hospitalized longer than influenza patients (six days [IQR 4-21] vs. 3 [2-4], p<.001). CONCLUSIONS: Bilateral GGOs and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.


Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Influenza, Human/epidemiology , Orthomyxoviridae/pathogenicity , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/virology , Comorbidity , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Female , Finland/epidemiology , Hospitalization , Humans , Incidence , Influenza, Human/diagnosis , Influenza, Human/mortality , Influenza, Human/virology , Intensive Care Units , Male , Middle Aged , Prospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Survival Analysis , Tertiary Care Centers , Tomography, X-Ray Computed
10.
Nat Biotechnol ; 39(6): 717-726, 2021 06.
Article in English | MEDLINE | ID: covidwho-1065901

ABSTRACT

Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections.


Subject(s)
COVID-19/therapy , Influenza, Human/therapy , RNA, Messenger/pharmacology , SARS-CoV-2/genetics , Animals , COVID-19/genetics , COVID-19/virology , CRISPR-Cas Systems/genetics , Cricetinae , Disease Models, Animal , Humans , Influenza, Human/genetics , Influenza, Human/virology , Mice , Orthomyxoviridae/drug effects , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , RNA, Messenger/genetics , RNA, Viral/genetics , Respiratory System/drug effects , Respiratory System/metabolism , SARS-CoV-2/pathogenicity
11.
PLoS One ; 15(12): e0243735, 2020.
Article in English | MEDLINE | ID: covidwho-1067396

ABSTRACT

INTRODUCTION: Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of respiratory viruses in wheezing children, it remains unclear if and how these viruses are associated with wheezing. The objective of this systematic review is to clarify the prevalence of different respiratory viruses in children with wheezing. METHODS: We performed an electronic in Pubmed and Global Index Medicus on 01 July 2019 and manual search. We performed search of studies that have detected common respiratory viruses in children ≤18 years with wheezing. We included only studies using polymerase chain reaction (PCR) assays. Study data were extracted and the quality of articles assessed. We conducted sensitivity, subgroup, publication bias, and heterogeneity analyses using a random effects model. RESULTS: The systematic review included 33 studies. Rhinovirus, with a prevalence of 35.6% (95% CI 24.6-47.3, I2 98.4%), and respiratory syncytial virus, at 31.0% (95% CI 19.9-43.3, I2 96.4%), were the most common viruses detected. The prevalence of other respiratory viruses was as follows: human bocavirus 8.1% (95% CI 5.3-11.3, I2 84.6%), human adenovirus 7.7% (95% CI 2.6-15.0, I2 91.0%), influenza virus6.5% (95% CI 2.2-12.6, I2 92.4%), human metapneumovirus5.8% (95% CI 3.4-8.8, I2 89.0%), enterovirus 4.3% (95% CI 0.1-12.9, I2 96.2%), human parainfluenza virus 3.8% (95% CI 1.5-6.9, I2 79.1%), and human coronavirus 2.2% (95% CI 0.6-4.4, I2 79.4%). CONCLUSIONS: Our results suggest that rhinovirus and respiratory syncytial virus may contribute to the etiology of wheezing in children. While the clinical implications of molecular detection of respiratory viruses remains an interesting question, this study helps to illuminate the potential of role respiratory viruses in pediatric wheezing. REVIEW REGISTRATION: PROSPERO, CRD42018115128.


Subject(s)
Respiratory Sounds/etiology , Respiratory Sounds/genetics , Respiratory Tract Infections/diagnosis , Bocavirus/genetics , Bocavirus/isolation & purification , Bocavirus/pathogenicity , Child , Child, Preschool , Coronavirus/isolation & purification , Coronavirus/pathogenicity , Humans , Orthomyxoviridae/genetics , Orthomyxoviridae/isolation & purification , Orthomyxoviridae/pathogenicity , Parainfluenza Virus 1, Human/genetics , Parainfluenza Virus 1, Human/isolation & purification , Parainfluenza Virus 1, Human/pathogenicity , Polymerase Chain Reaction , Respiratory Sounds/physiopathology , Respiratory System/pathology , Respiratory System/virology , Respiratory Tract Infections/genetics , Respiratory Tract Infections/virology
13.
PLoS One ; 15(12): e0242954, 2020.
Article in English | MEDLINE | ID: covidwho-992692

ABSTRACT

Coronaviruses and influenza viruses have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Coronaviruses had fewer variations than a subclass of influenza viruses. In addition, differences among coronaviruses that infect a variety of hosts were also small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for new pandemics.


Subject(s)
COVID-19/virology , Pandemics , Polymorphism, Genetic , SARS-CoV-2/pathogenicity , Seasons , COVID-19/epidemiology , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Orthomyxoviridae/genetics , Orthomyxoviridae/pathogenicity , Principal Component Analysis , SARS-CoV-2/genetics
14.
Molecules ; 25(21)2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-983191

ABSTRACT

Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.


Subject(s)
Coronavirus Infections/therapy , Influenza, Human/therapy , Mental Disorders/therapy , Multiple Sclerosis/therapy , Pneumonia, Viral/therapy , Probiotics/therapeutic use , Respiratory Tract Infections/therapy , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , Brain/immunology , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/microbiology , Coronavirus Infections/virology , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/microbiology , Humans , Immunomodulation , Influenza, Human/immunology , Influenza, Human/microbiology , Influenza, Human/virology , Lung/immunology , Mental Disorders/immunology , Mental Disorders/microbiology , Microbial Consortia/immunology , Multiple Sclerosis/immunology , Multiple Sclerosis/microbiology , Orthomyxoviridae/drug effects , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/microbiology , Pneumonia, Viral/virology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/microbiology , SARS-CoV-2 , Symbiosis/immunology
15.
Molecules ; 25(21)2020 Oct 22.
Article in English | MEDLINE | ID: covidwho-983187

ABSTRACT

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Herpes Simplex/drug therapy , Influenza, Human/drug therapy , Phytochemicals/therapeutic use , Pneumonia, Viral/drug therapy , Antiviral Agents/chemistry , Antiviral Agents/classification , Antiviral Agents/isolation & purification , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Drug Discovery , HIV/drug effects , HIV/pathogenicity , HIV/physiology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/pathogenicity , Hepacivirus/physiology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpes Simplex/pathology , Herpes Simplex/virology , Humans , Influenza, Human/pathology , Influenza, Human/virology , Orthomyxoviridae/drug effects , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Pandemics , Phytochemicals/chemistry , Phytochemicals/classification , Phytochemicals/isolation & purification , Plants, Medicinal , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2 , Simplexvirus/drug effects , Simplexvirus/pathogenicity , Simplexvirus/physiology , Virus Internalization/drug effects , Virus Replication/drug effects
16.
FEBS J ; 287(17): 3672-3676, 2020 09.
Article in English | MEDLINE | ID: covidwho-960854

ABSTRACT

The novel coronavirus SARS-CoV-2 is the causative agent of the global coronavirus disease 2019 (COVID-19) outbreak. In addition to pneumonia, other COVID-19-associated symptoms have been reported, including loss of smell (anosmia). However, the connection between infection with coronavirus and anosmia remains enigmatic. It has been reported that defects in olfactory cilia lead to anosmia. In this Viewpoint, we summarize transmission electron microscopic studies of cilia in virus-infected cells. In the human nasal epithelium, coronavirus infects the ciliated cells and causes deciliation. Research has shown that viruses such as influenza and Sendai attach to the ciliary membrane. The Sendai virus enters cilia by fusing its viral membrane with the ciliary membrane. A recent study on SARS-CoV-2-human protein-protein interactions revealed that the viral nonstructural protein Nsp13 interacts with the centrosome components, providing a potential molecular link. The mucociliary escalator removes inhaled pathogenic particles and functions as the first line of protection mechanism against viral infection in the human airway. Thus, future investigation into the virus-cilium interface will help further the battle against COVID-19.


Subject(s)
Anosmia/metabolism , COVID-19/metabolism , Centrosome/virology , Cilia/virology , Nasal Mucosa/virology , SARS-CoV-2/pathogenicity , Viral Nonstructural Proteins/metabolism , Anosmia/complications , Anosmia/physiopathology , Anosmia/virology , COVID-19/complications , COVID-19/physiopathology , COVID-19/virology , Centrosome/metabolism , Centrosome/ultrastructure , Cilia/metabolism , Cilia/ultrastructure , Host-Pathogen Interactions/genetics , Humans , Methyltransferases/genetics , Methyltransferases/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Nasal Mucosa/metabolism , Nasal Mucosa/ultrastructure , Orthomyxoviridae/metabolism , Orthomyxoviridae/pathogenicity , Protein Binding , RNA Helicases/genetics , RNA Helicases/metabolism , SARS-CoV-2/metabolism , Sendai virus/metabolism , Sendai virus/pathogenicity , Severity of Illness Index , Smell/physiology , Viral Nonstructural Proteins/genetics
19.
Vaccine ; 38(45): 7049-7056, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-752762

ABSTRACT

BACKGROUND: Maintaining health of healthcare workers with vaccination is a major component of pandemic preparedness and acceptance of vaccinations is essential to its success. This study aimed to examine impact of the coronavirus disease 2019 (COVID-19) pandemic on change of influenza vaccination acceptance and identify factors associated with acceptance of potential COVID-19 vaccination. METHOD: A cross-sectional self-administered anonymous questionnaire survey was conducted among nurses in Hong Kong, China during 26 February and 31 March 2020. Their previous acceptance of influenza vaccination and intentions to accept influenza and COVID-19 vaccination were collected. Their relationship with work-related and other factors were examined using multiple multinomial logistic regressions. RESULTS: Responses from 806 participants were retrieved. More nurses changed from vaccination refusal to hesitancy or acceptance than those changed from acceptance to vaccination hesitancy or refusal (15.5% vs 6.8% among all participants, P < 0.001). 40.0% participants intended to accept COVID-19 vaccination, and those in private sector (OR: 1.67, 95%CI: 1.11-2.51), with chronic conditions (OR: 1.83, 95%CI: 1.22-2.77), encountering with suspected or confirmed COVID-19 patients (OR: 1.63, 95%CI: 1.14-2.33), accepted influenza vaccination in 2019 (OR: 2.03, 95%CI: 1.47-2.81) had higher intentions to accept it. Reasons for refusal and hesitation for COVID-19 vaccination included "suspicion on efficacy, effectiveness and safety", "believing it unnecessary", and "no time to take it". CONCLUSION: With a low level of COVID-19 acceptance intentions and high proportion of hesitation in both influenza and COVID-19 vaccination, evidence-based planning are needed to improve the uptake of both vaccinations in advance of their implementation. Future studies are needed to explore reasons of change of influenza vaccination acceptance, look for actual behaviour patterns of COVID-19 vaccination acceptance and examine effectiveness of promotion strategies.


Subject(s)
Coronavirus Infections/prevention & control , Coronavirus Infections/psychology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Influenza, Human/psychology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/psychology , Vaccination/psychology , Adolescent , Adult , Age Factors , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Cross-Sectional Studies , Female , Health Personnel , Hong Kong/epidemiology , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/epidemiology , Influenza, Human/immunology , Intention , Male , Middle Aged , Orthomyxoviridae/pathogenicity , Patient Acceptance of Health Care/psychology , Patient Safety , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , SARS-CoV-2 , Sex Factors , Surveys and Questionnaires , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
20.
Pathog Dis ; 78(7)2020 10 07.
Article in English | MEDLINE | ID: covidwho-733382

ABSTRACT

Influenza virus and coronaviruses continue to cause pandemics across the globe. We now have a greater understanding of their functions. Unfortunately, the number of drugs in our armory to defend us against them is inadequate. This may require us to think about what mechanisms to address. Here, we review the biological properties of these viruses, their genetic evolution and antiviral therapies that can be used or have been attempted. We will describe several classes of drugs such as serine protease inhibitors, heparin, heparan sulfate receptor inhibitors, chelating agents, immunomodulators and many others. We also briefly describe some of the drug repurposing efforts that have taken place in an effort to rapidly identify molecules to treat patients with COVID-19. While we put a heavy emphasis on the past and present efforts, we also provide some thoughts about what we need to do to prepare for respiratory viral threats in the future.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/epidemiology , Coronavirus/drug effects , Drug Repositioning , Influenza, Human/epidemiology , Orthomyxoviridae/drug effects , Pandemics , Anticoagulants/therapeutic use , Antimalarials/therapeutic use , Antioxidants/therapeutic use , Chelating Agents/therapeutic use , Coronavirus/genetics , Coronavirus/growth & development , Coronavirus/pathogenicity , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Glycoconjugates/therapeutic use , Humans , Immunologic Factors/therapeutic use , Influenza, Human/drug therapy , Influenza, Human/virology , Orthomyxoviridae/genetics , Orthomyxoviridae/growth & development , Orthomyxoviridae/pathogenicity , Serine Proteinase Inhibitors/therapeutic use
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