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1.
J Vis Exp ; (187)2022 09 07.
Article in English | MEDLINE | ID: covidwho-2217149

ABSTRACT

Virus infections have a major impact on society; most methods of detection have difficulties in determining whether a detected virus is infectious, causing delays in treatment and further spread of the virus. Developing new sensors that can inform on the infectability of clinical or environmental samples will meet this unmet challenge. However, very few methods can obtain sensing molecules that can recognize an intact infectious virus and differentiate it from the same virus that has been rendered non-infectious by disinfection methods. Here, we describe a protocol to select aptamers that can distinguish infectious viruses vs non-infectious viruses using systematic evolution of ligands by exponential enrichment (SELEX). We take advantage of two features of SELEX. First, SELEX can be tailor-made to remove competing targets, such as non-infectious viruses or other similar viruses, using counter selection. Additionally, the whole virus can be used as the target for SELEX, instead of, for example, a viral surface protein. Whole virus SELEX allows for the selection of aptamers that bind specifically to the native state of the virus, without the need to disrupt of the virus. This method thus allows recognition agents to be obtained based on functional differences in the surface of pathogens, which do not need to be known in advance.


Subject(s)
Aptamers, Nucleotide , Virus Diseases , Viruses , Aptamers, Nucleotide/metabolism , Humans , Ligands , Membrane Proteins , SELEX Aptamer Technique/methods , Viruses/metabolism
2.
Int J Mol Sci ; 23(7)2022 Mar 26.
Article in English | MEDLINE | ID: covidwho-2216279

ABSTRACT

Viruses infect all types of organisms, causing viral diseases, which are very common in humans. Since viruses use the metabolic pathways of their host cells to replicate, they are difficult to eradicate without affecting the cells. The most effective measures against viral infections are vaccinations and antiviral drugs, which selectively inhibit the viral replication cycle. Both methods have disadvantages, which requires the development of new approaches to the treatment of viral diseases. In the study of animal venoms, it was found that, in addition to toxicity, venoms exhibit other types of biological activity, including an antiviral one, the first mention of which dates back to middle of the last century, but detailed studies of their antiviral activity have been conducted over the past 15 years. The COVID-19 pandemic has reinforced these studies and several compounds with antiviral activity have been identified in venoms. Some of them are very active and can be considered as the basis for antiviral drugs. This review discusses recent antiviral studies, the found compounds with high antiviral activity, and the possible mechanisms of their action. The prospects for using the animal venom components to create antiviral drugs, and the expected problems and possible solutions are also considered.


Subject(s)
COVID-19 , Virus Diseases , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Pandemics , Virus Diseases/drug therapy
3.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.30.23285171

ABSTRACT

Rapid molecular diagnostic tests have been critical in the response to the COVID-19 pandemic. It is important to evaluate the ability of these assays to identify variants of concern, particularly across varying collection and storage conditions. Nasal swabs positive for Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.167.2), Gamma (P.1), or Omicron (B.1.1.529) variants of concern (VOCs) were stored in TE buffer and viral transport media (VTM). We evaluated the sensitivity of the Cepheid Xpert(R) Xpress SARS-CoV-2 assay in detecting VOC samples and validated TE buffer for use with the assay. Testing of known VOC positives revealed no substantial reduction of PCR sensitivity. Comparison of TE and VTM samples also revealed no reduction in performance when using TE buffer, validating the use of TE buffer to store SARS-CoV-2 samples. SARS-CoV-2 VOCs collected and stored across various conditions can be detected by the Cepheid Xpert(R) Xpress SARS-CoV-2 assay.


Subject(s)
COVID-19 , Virus Diseases
4.
Viruses ; 14(11)2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2200863

ABSTRACT

Chemokines constitute a group of small, secreted proteins that regulate leukocyte migration and contribute to their activation. Chemokines are crucial inflammatory mediators that play a key role in managing viral infections, during which the profile of chemokine expression helps shape the immune response and regulate viral clearance, improving clinical outcome. In particular, the chemokine ligand CXCL10 and its receptor CXCR3 were explored in a plethora of RNA and DNA viral infections. In this review, we highlight the expression profile and role of the CXCL10/CXCR3 axis in the host defense against a variety of RNA and DNA viral infections. We also discuss the interactions among viruses and host cells that trigger CXCL10 expression, as well as the signaling cascades induced in CXCR3 positive cells.


Subject(s)
Chemokine CXCL10 , Virus Diseases , Humans , Chemokine CXCL10/genetics , RNA , Virus Diseases/genetics , DNA
5.
Cytokine ; 157: 155962, 2022 09.
Article in English | MEDLINE | ID: covidwho-2177976

ABSTRACT

Considerable evidence supports that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in various neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. The purpose of this study is to discuss the recent research on treating cytokine storm and amyloids, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's condition, Multi-sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation observed in neurological disorders has a pivotal role in exacerbating Aß burden and tau hyperphosphorylation, suggesting that stimulating cytokines in response to an undesirable external response could be a checkpoint for treating neurological disorders. Furthermore, the pro-inflammatory cytokines help our immune system through a neuroprotective mechanism in clearing viral infection by recruiting mononuclear cells. This study reveals that cytokine applications may play a vital role in providing novel regulation and methods for the therapeutic approach to neurological disorders and the causes of the deregulation, which is responsible for neuroinflammation and viral infection. However, it needs to be further investigated to clarify better the mechanisms of cytokine release in response to various stimuli, which could be the central point for treating neurological disorders.


Subject(s)
Alzheimer Disease , Nervous System Diseases , Virus Diseases , Cytokines/physiology , Humans , Nervous System Diseases/therapy , Neuroinflammatory Diseases
6.
authorea preprints; 2023.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.167516102.26003022.v1

ABSTRACT

ABSTRACT Introduction: Influenza is an acute viral infection with significant morbidity and mortality. Its occur annually each winter is called seasonal influenza and is preventable through safe vaccine. Aim: To know the epidemiological pattern of patients with seasonal influenza in Iraqi sentinel sites. Methods: A cross- sectional study carried out on records of patients who attended four sentinel sites and registered to have influenza-like illness (ILI) or severe acute respiratory infection (SARI), and laboratory investigated. Results: The total number of cases was 1124, 36.2% of them aged 19-39 years; 53.9% were female; 74.9% lived in urban areas; 64.3% diagnosed as ILI and 35.7% as SARI. 15.9% had diabetes, 12.7% had heart disease, 4.8% had asthma, 3% had a chronic lung disease, and 2% had hematological disease. 94.6% did not get influenza vaccine. About COVID-19 vaccine, 69.4% did not vaccinated, 3.5% get only 1 dose, and 27.1% completed 2 doses. Only the SARI cases needed admission, among them 95.7% were cured. 6.5% were diagnosed as influenza- A virus, 26.1% had COVID-19, and 67.5% were negative. Among those with influenza, 97.3% had H3N2 subtype, and 2.7% had H1N1 pdm09. Conclusions: The percentage of influenza virus in Iraq is relatively small. The age, classification of case (ILI or SARI), having diabetes, heart disease, or immunological disease, and taking COVID-19 vaccine have a significant association with influenza. Recommendations: It’s needed for similar sentinel sites in other health directorates and for rising health education about seasonal influenza and its vaccine.


Subject(s)
Respiratory Tract Infections , Hematologic Diseases , Diabetes Mellitus , Severe Acute Respiratory Syndrome , Heart Diseases , Asthma , COVID-19 , Lung Diseases , Immune System Diseases , Virus Diseases
7.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.28.526023

ABSTRACT

Pandemic caused by viral protein is characterized by waves of transmission triggered by new variants replacing old ones, resulting in immune escape and threatening public health. Therefore, there is an obvious need to accurately identify the vital mutation sites and understand the complex patterns of mutation effect of viral protein. However, existing work do not explicitly modelling vital positions functioning for virus fitness, leading to large search space with money- and time-consuming search cost. Here, we propose EVPMM (evolutionary integrated viral protein mutation machine), a co-evolution profiles integrated deep learning framework for dominant variants forecasting, vital mutation sites prediction and fitness landscape depicting. It consists of a position detector to directly detect the functional positions as well as a mutant predictor to depict fitness landscape. Moreover, pairwise dependencies between residues obtained by a Markov Random Field are also incorporated to promote reasonable variant generation. We show that EVPMM significantly outperforms existing machine learning algorithms on mutation position detection, residue prediction and fitness prediction accuracies. Remarkably, there is a highly agreement between positions identified by our method with current variants of concern and provides some new mutation pattern hypothesis. The method can prioritize mutations as they emerge for public health concern.


Subject(s)
Seizures , Virus Diseases
8.
authorea preprints; 2023.
Preprint in English | PREPRINT-AUTHOREA PREPRINTS | ID: ppzbmed-10.22541.au.167479979.96721298.v1

ABSTRACT

Background: – The incidence of pediatric asthma exacerbations during the COVID-19 pandemic has been evaluated; however, the incidence of severe acute asthma (SAA) requiring a Pediatric Intensive Care Unit (PICU) admission is unknown. Furthermore, we examined several factors which might influence this incidence, such as environmental triggers or changes in COVID-19 lockdown regulations. Methods: – In this single-center, retrospective cohort study running from 2018 to 2021, all PICU admissions for SAA of children above two years of age at a tertiary hospital in the Netherlands were included. Information on potential asthma triggers during the pandemic, including viral infections, concentrations of ambient fine particulate matter (PM2.5) and pollen index were evaluated. Results: – In total, 168 children were included in this study. While we observed a decrease in PICU admissions for SAA during lockdown periods, there was an increase in the admission rates in the periods without a lockdown, with the highest peak from August to November of 2021. This peak in the fall of 2021 did not align with pollen or ambient PM2.5 concentrations (r =-0.04 for pollen and r =0.23 for PM2.5). Discussion: – COVID-19 lockdowns influenced the admission rates for SAA at the PICU both during and after the lockdowns in the Netherlands. We hypothesize that an increase in viral infections after lockdown periods was the reason for the altered incidence of SAA at the PICU in late 2021, rather than air pollution and pollen concentrations.


Subject(s)
Virus Diseases , COVID-19 , Asthma
9.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2508557.v1

ABSTRACT

Background: The particle structure of Emiliania huxleyi virus (EhV), an algal infecting member of nucleocytoplasmic large DNA viruses (NCLDVs), contains an outer lipid membrane envelope similar to that found in animal viruses such as African swine fever virus (ASFV). Despite both being enveloped NCLDVs, EhV and ASFV are known for their stability in the environment. Method: Here we report for the first time, the application of a viability PCR method to describe the unprecedented and similar virion thermal stability of both EhV and ASFV. This result contradicts the bioassay method that suggests that virus “infectivity” is lost in a matter of seconds (EhV) and minutes (ASFV) at temperature greater than 50 °C. Confocal microscopy and analytical flow cytometry methods was used to validate the viability PCR data for EhV. Results: We observed that both EhV and ASFV particles has unprecedented thermal tolerances. These two NCLDVs are exceptions to the rule that having an enveloped virion anatomy is a predicted weakness, as is often observed in enveloped RNA viruses (i.e., the viruses causing Porcine Reproductive and Respiratory Syndrome (PRRS), COVID-19, Ebola, or seasonal influenza). Using the viability PCR method, we confirm that no PRRSV particles remain after 20 minutes of exposure to temperatures up to 100 °C. Conclusions: This observation has practical implications for industries involved in animal health and food security. Finally, we propose that EhV could be used as a surrogate for ASFV under certain circumstances.


Subject(s)
Respiratory Insufficiency , Muscle Weakness , COVID-19 , Fever , Virus Diseases , Porcine Reproductive and Respiratory Syndrome
10.
arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2301.09189v1

ABSTRACT

The coronavirus pandemic (COVID) has been an exceptional test of current scientific evidence that inform and shape policy. Many US states, cities, and counties implemented public orders for mask use on the notion that this intervention would delay and flatten the epidemic peak and largely benefit public health outcomes. P-value plotting was used to evaluate statistical reproducibility of meta-analysis research claims of a benefit for medical (surgical) mask use in community settings to prevent COVID infection. Eight studies (seven meta-analyses, one systematic review) published between 1 January 2020 and 7 December 2022 were evaluated. Base studies were randomized control trials with outcomes of medical diagnosis or laboratory-confirmed diagnosis of viral (Influenza or COVID) illness. Self-reported viral illness outcomes were excluded because of awareness bias. No evidence was observed for a medical mask use benefit to prevent viral infections in six p-value plots (five meta-analyses and one systematic review). Research claims of no benefit in three meta-analyses and the systematic review were reproduced in p-value plots. Research claims of a benefit in two meta-analyses were not reproduced in p-value plots. Insufficient data were available to construct p-value plots for two meta-analyses because of overreliance on self-reported outcomes. These findings suggest a benefit for medical mask use in community settings to prevent viral, including COVID infection, is unproven.


Subject(s)
Intraoperative Awareness , Coronavirus Infections , Virus Diseases
11.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2501769.v1

ABSTRACT

The sudden outbreak of the Corona Virus Disease 2019 (COVID-19) broke the stable trend of air quality improvement in Chinese cities due to the emergency response measures, such as the lockdown policy. In this study, 333 Chinese cities are divided into six levels by economic factors, such as first-tier, new first-tier, second-tier, third-tier, fourth-tier, and fifth-tier, and the time of each year was defined as pre-lockdown, lockdown and reopen periods. The results show that, during the pre-lockdown period, the concentrations of NO2 and PM2.5 decreased by 10.13% and 6.15%, respectively, compared with the same period averages in 2017–2019. The fifth-tier cities have the minimum reductions of NO2 and PM2.5. The lockdown policy has significantly improved the air quality in Chinese cities during the COVID-19 pandemic. The concentrations of NO2 and PM2.5 decreased by 42.38% and 29.34%, respectively, but the air quality of first-tier cities was least affected by lockdown. During the reopen period, the concentrations of NO2 and PM2.5 decreased by 14.28% and 25.71%, respectively, and the NO2 concentrations in each city are similar for the season. The NO2 and PM2.5 concentrations in 2020 without lockdown were estimated through a multivariate linear regression model. The actual values of both NO2 and PM2.5 concentrations during the lockdown period are lower than the projected values based on the 2017–2019 trend, again indicating that the lockdown policy influences their concentrations.


Subject(s)
Virus Diseases , COVID-19
12.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.16.22283804

ABSTRACT

In COVID-19 neurological alterations are noticed during the systemic viral infection. Various pathophysiological mechanisms on the central nervous system (CNS) have been suggested in the past two years, including the viral neurotropism hypothesis. Nevertheless, neurological complications can also occur independent of neurotropism and at different stages of the disease and may be persistent. Previous autopsy studies of the CNS from patients with severe COVID-19 show infiltration of macrophages and T lymphocytes, especially in the perivascular regions as well as pronounced microglial activation, but without signs of viral encephalitis. However, there is an ongoing debate about long-term changes and cytotoxic effects in the CNS due to the systemic inflammation. Here, we show the brain-specific host response during and after COVID-19. We profile single-nucleus transcriptomes and proteomes of brainstem tissue from deceased COVID-19 patients who underwent rapid autopsy. We detect a disease phase-dependent inflammatory type-I interferon response in acute COVID-19 cases. Integrating single-nucleus RNA sequencing and spatial transcriptomics, we could localize two patterns of reaction to severe systemic inflammation. One neuronal with direct focus on cranial nerve nuclei and one diffusely affecting the whole brainstem, the latter reflecting a bystander effect that spreads throughout the vascular unit and alters the transcriptional state of oligodendrocytes, microglia and astrocytes. Our results indicate that even without persistence of SARS-CoV-2 in the CNS, the tissue activates highly protective mechanisms, which also cause functional disturbances that may explain the neurological symptoms of COVID-19, triggered by strong systemic type-I IFN signatures in the periphery.


Subject(s)
Encephalitis, Viral , Virus Diseases , COVID-19 , Inflammation
13.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.13.524025

ABSTRACT

With the alarming surge in COVID-19 cases globally, vaccination must be prioritised to achieve herd immunity. Immune dysfunction is detected in the majority of patients with COVID-19; however, it remains unclear whether the immune responses elicited by COVID-19 vaccination function against the Omicron subvariant BA.2. Of the 508 Omicron BA.2-infected patients enrolled, 102 were unvaccinated controls and 406 were vaccinated. Despite the presence of clinical symptoms in both groups, vaccination led to a significant decline in nausea or vomiting, abdominal pain, headache, pulmonary infection, overall clinical symptoms, and a moderate rise in body temperature. Omicron BA.2-infected individuals were also characterised by a mild increase in both serum pro- and anti-inflammatory cytokine levels after vaccination. There were no significant differences or trend changes between T and B lymphocyte subsets; however, a significant expansion of NK lymphocytes in COVID-19-vaccinated patients was observed. Moreover, the most effective CD16brightCD56dim subsets of NK cells showed increased functional capacities, as evidenced by a significantly greater IFN-{gamma} secretion and stronger cytotoxic potential in Omicron BA.2-infected patients after vaccination. Collectively, these results suggest that COVID-19 vaccination interventions promote the redistribution and activation of CD16brightCD56dim NK cell subsets against viral infections, and could facilitate the clinical management of Omicron BA.2-infected patients.


Subject(s)
Postoperative Nausea and Vomiting , Infections , Headache , Pulmonary Embolism , Abdominal Pain , COVID-19 , Virus Diseases
14.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.10.523518

ABSTRACT

Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks. We have screened a library of microbial metabolites to discover new SARS-CoV-2 inhibitors. To facilitate this screening effort, we generated a recombinant SARS-CoV-2 Delta variant carrying the nano luciferase as a reporter for measuring viral infection. Six compounds were found to inhibit SARS-CoV-2 at the half maximal inhibitory concentration (IC50) below 1 mM, including the anthracycline drug aclarubicin that markedly reduced viral RNA-dependent RNA polymerase (RdRp)-mediated gene expression, whereas other anthracyclines inhibited SARS-CoV-2 by activating the expression of interferon and antiviral genes. As the most commonly prescribed anti-cancer drugs, anthracyclines hold the promise of becoming new SARS-CoV-2 inhibitors.


Subject(s)
Virus Diseases , COVID-19
15.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.01.03.23284127

ABSTRACT

Objectives In a dangerous future pandemic without effective vaccines and medicines, a reliable screening-and-isolation strategy can be the last opportunity to keep critical facilities and communities running and avoid a complete shutdown. Methods In this study, we introduced an epidemiological model that included essential parameters of infection transmission and screening. With varying parameters, we studied the dynamics of viral infection in the semi-isolated communities. Results In the scenario with a periodic infection screening once per 3 days and a viral basic reproduction number 3.0, more than 85% of the infection waves have a duration less than 7 days and the infection size in each of the waves is generally less than 4 individuals when the efficiency of infection discovery is 0.9 in the screening. When the period of screening was elongated to once per 7 days, the cases of infection dramatically increased to 5 folds of that mentioned previously. Further, with a weak discovery efficiency of 0.7 and the aforementioned low screening frequency, the spread of infection would be out of control. Conclusions Our study suggests that frequent periodic screening is capable of controlling a future epidemic in a semi-isolated community without vaccines and medicines.


Subject(s)
Virus Diseases
16.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.01.522328

ABSTRACT

microRNAs (miRNAs) inhibit mRNA translation initiation by recruiting the GIGYF2/4EHP translation repressor complex to the mRNA 5' cap structure. Viruses utilise miRNAs to impair the host antiviral immune system and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. We recently reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein 2 (NSP2) interacts with GIGYF2. This interaction is critical for blocking translation of the Ifn1-b mRNA that encodes the cytokine Interferon-beta, and thereby impairs the host antiviral immune response. However, it is not known whether NSP2 also affects miRNA-mediated silencing. Here, we demonstrate the pervasive augmentation of the miRNA-mediated translational repression of cellular mRNAs by NSP2. We show that NSP2 interacts with Argonaute 2, the core component of the miRNA-Induced Silencing Complex (miRISC) and enhances the translational repression mediated by natural miRNA binding sites in the 3' UTR of cellular mRNAs. Our data reveal an additional layer of the complex mechanism by which SARS-CoV-2 and likely other coronaviruses manipulate the host gene expression program through co-opting the host miRNA-mediated silencing machinery.


Subject(s)
Coronavirus Infections , Virus Diseases
17.
preprints.org; 2022.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202212.0577.v1

ABSTRACT

Background: Signaling by toll like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro. Material & methods: 30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex matched control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8 and 9 agonists, the spike protein (SP) of SARS-CoV-2 and the Receptor Binding Domain (RBD) unit of SP. Frequencies of CD3+IFN-β+ T cells, and CD3+IFN-g+ T cells was evaluated by flow cytometry. Interferon (IFN)-b gene expression was assessed by qRT-PCR. Results: The frequency of CD3+IFN-β+ T cells was higher in moderate and severe patients at baseline in comparison with HCs. Stimulation of PBMCs from moderate patients with SP and TLR8 agonist significantly upregulated the frequency of CD3+IFN-β+ T cells (P=0.0005 and 0.0024, respectively) when compared to non-stimulated (NS) samples. The greatest increase in CD3+IFN-b+ T cell frequency in PBMCs from severe patients was seen with TLR8 and TLR7 agonists when compared to NS (P= 0.003 and 0.0167, respectively). TLR stimulation did not significantly enhance the frequency of CD3+IFN-g+ T cells generated from PBMCs from moderate and severe patients compared with unstimulated controls. However, the frequency of CD3+IFN-ɣ+ T cells in PBMCs from moderate patients was upregulated by agonists of TLR3, 8 and 9, SP and RBD when compared with NS samples from HCs. The expression of the IFN-β gene after stimulation of CD3+T cells with the TLR8 agonist was also up-regulated in moderate than severe patients (moderate vs. severe: p=0.0006). In addition, stimulation of CD3+ T cells with SP, up-regulated the expression of IFN-β gene expression in cells from patients with moderate disease (moderate vs. severe: p=0.01). Conclusion: Stimulation of PBMCs from COVID-19 patients with a TLR8 agonist and with SP enhanced IFN-b protein and gene levels. This may potentiate immune responses against SARS-CoV-2 infection and prevent viral replication and spread.


Subject(s)
Severe Acute Respiratory Syndrome , COVID-19 , Cystitis , Virus Diseases
18.
J Biomed Sci ; 29(1): 55, 2022 Jul 31.
Article in English | MEDLINE | ID: covidwho-1965824

ABSTRACT

BACKGROUND: Infections by viruses including severe acute respiratory syndrome coronavirus 2 could cause organ inflammations such as myocarditis, pneumonia and encephalitis. Innate immunity to viral nucleic acids mediates antiviral immunity as well as inflammatory organ injury. However, the innate immune mechanisms that control viral induced organ inflammations are unclear. METHODS: To understand the role of the E3 ligase TRIM18 in controlling viral myocarditis and organ inflammation, wild-type and Trim18 knockout mice were infected with coxsackievirus B3 for inducing viral myocarditis, influenza A virus PR8 strain and human adenovirus for inducing viral pneumonia, and herpes simplex virus type I for inducing herpes simplex encephalitis. Mice survivals were monitored, and heart, lung and brain were harvested for histology and immunohistochemistry analysis. Real-time PCR, co-immunoprecipitation, immunoblot, enzyme-linked immunosorbent assay, luciferase assay, flow cytometry, over-expression and knockdown techniques were used to understand the molecular mechanisms of TRIM18 in regulating type I interferon (IFN) production after virus infection in this study. RESULTS: We find that knockdown or deletion of TRIM18 in human or mouse macrophages enhances production of type I IFN in response to double strand (ds) RNA and dsDNA or RNA and DNA virus infection. Importantly, deletion of TRIM18 protects mice from viral myocarditis, viral pneumonia, and herpes simplex encephalitis due to enhanced type I IFN production in vivo. Mechanistically, we show that TRIM18 recruits protein phosphatase 1A (PPM1A) to dephosphorylate TANK binding kinase 1 (TBK1), which inactivates TBK1 to block TBK1 from interacting with its upstream adaptors, mitochondrial antiviral signaling (MAVS) and stimulator of interferon genes (STING), thereby dampening antiviral signaling during viral infections. Moreover, TRIM18 stabilizes PPM1A by inducing K63-linked ubiquitination of PPM1A. CONCLUSIONS: Our results indicate that TRIM18 serves as a negative regulator of viral myocarditis, lung inflammation and brain damage by downregulating innate immune activation induced by both RNA and DNA viruses. Our data reveal that TRIM18 is a critical regulator of innate immunity in viral induced diseases, thereby identifying a potential therapeutic target for treatment.


Subject(s)
Encephalitis, Herpes Simplex , Myocarditis , Ubiquitin-Protein Ligases , Virus Diseases , Animals , Antiviral Agents , Humans , Immunity, Innate , Inflammation/genetics , Mice , Myocarditis/genetics , Myocarditis/virology , Protein Phosphatase 2C , RNA , Ubiquitin-Protein Ligases/genetics
19.
BMC Pediatr ; 22(1): 452, 2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1965734

ABSTRACT

BACKGROUND: Pneumonia is a serious problem that threatens the health of newborns. This study aimed to investigate the clinical characteristics of hospitalized term and preterm infants with community-acquired viral pneumonia. METHODS: This was a retrospective analysis of cases of community-acquired viral pneumonia in the Neonatal Department. Nasopharyngeal aspirate (NPA) samples were collected for pathogen detection, and clinical data were collected. We analysed pathogenic species and clinical characteristics among these infants. RESULTS: RSV is the main virus in term infants, and parainfluenza virus (PIV) 3 is the main virus in preterm infants. Patients infected with PIV3 were more susceptible to coinfection with bacteria than those with respiratory syncytial virus (RSV) infection (p < 0.05). Preterm infants infected with PIV3 were more likely to be coinfected with bacteria than term infants (p < 0.05), mainly gram-negative bacteria (especially Klebsiella pneumonia). Term infants with bacterial infection were more prone to fever, cyanosis, moist rales, three concave signs, elevated C-reactive protein (CRP) levels, respiratory failure and the need for higher level of oxygen support and mechanical ventilation than those with simple viral infection (p < 0.05). The incidence of hyponatremia in neonatal community-acquired pneumonia (CAP) was high. CONCLUSIONS: RSV and PIV3 were the leading causes of neonatal viral CAP. PIV3 infection is the main cause of viral CAP in preterm infants, and these individuals are more likely to be coinfected with bacteria than term infants, mainly gram-negative bacteria. Term infants with CAP coinfected with bacteria were more likely to have greater disease severity than those with single viral infections.


Subject(s)
Community-Acquired Infections , Pneumonia, Viral , Respiratory Syncytial Virus Infections , Virus Diseases , Community-Acquired Infections/epidemiology , Humans , Infant , Infant, Newborn , Infant, Premature , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/epidemiology , Retrospective Studies
20.
BMC Public Health ; 22(1): 1167, 2022 06 11.
Article in English | MEDLINE | ID: covidwho-1885294

ABSTRACT

BACKGROUND: Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019. METHODS: We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES). RESULTS: After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for almost the half of all infections and that they exhibited the highest degree of seasonality. Coinfections of viruses are frequent; the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection. CONCLUSIONS: The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.


Subject(s)
Coinfection , Respiratory Tract Infections , Virus Diseases , Viruses , Coinfection/epidemiology , Humans , Infant , Rhinovirus , Virus Diseases/epidemiology
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