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1.
J Med Virol ; 93(11): 6116-6123, 2021 11.
Article in English | MEDLINE | ID: covidwho-1349155

ABSTRACT

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.


Subject(s)
Immunity, Innate , Pathogen-Associated Molecular Pattern Molecules/metabolism , Toll-Like Receptors/immunology , Toll-Like Receptors/metabolism , Viral Proteins/metabolism , Virus Diseases/immunology , Viruses/immunology , Animals , HIV/immunology , HIV/metabolism , HIV/pathogenicity , Hepacivirus/immunology , Hepacivirus/metabolism , Hepacivirus/pathogenicity , Herpesviridae/immunology , Herpesviridae/metabolism , Herpesviridae/pathogenicity , Humans , Measles virus/immunology , Measles virus/metabolism , Measles virus/pathogenicity , Pathogen-Associated Molecular Pattern Molecules/chemistry , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/metabolism , Respiratory Syncytial Viruses/pathogenicity , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Viral Proteins/chemistry , Virus Diseases/virology , Viruses/metabolism , Viruses/pathogenicity
2.
J Korean Med Sci ; 37(28): e215, 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1952226

ABSTRACT

BACKGROUND: Parainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) B epidemics occurred in South Korea in late 2021. We investigated epidemiological changes of PIV3 and RSV B infections in Korean children before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this multicenter retrospective study, we enrolled patients aged less than 19 years with PIV3 or RSV infection in four university hospitals from January 2018 to January 2022. Demographic and clinical data were extracted from the subject's medical records and analyzed for each virus. RESULTS: A total of 652 children with PIV3 were identified including three epidemics: 216 in 2018, 260 in 2019, and 167 in 2021. Among 627 RSV B cases, 169 were identified in 2017/2018, 274 in 2019/2020, and 115 in 2021/2022. The peak circulation of PIV3 and RSV B epidemics were delayed by 6 and 2 months, respectively, in 2021, compared with those in the pre-COVID-19 period. The median age of PIV3 infections increased in 2021 (21.5 months in 2021 vs. 13.0-14.0 in 2018-2019; P < 0.001), whereas that of RSV B infections remained unchanged (3.6-4.0 months). During the COVID-19 pandemic, less frequent hospitalization rates were observed for both PIV3 and RSV B infections, but more children needed respiratory assistance for RSV B infection in 2021/2022 epidemic (32.5%) than before (14.7-19.4%, P = 0.014). CONCLUSION: We observed changes in the epidemiology and clinical presentation of PIV3 and RSV B infections in Korean children during the COVID-19 pandemic.


Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Antibodies, Viral , COVID-19/epidemiology , Child , Humans , Infant , Pandemics , Parainfluenza Virus 3, Human , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Viruses , Retrospective Studies
3.
Emerg Med Australas ; 34(4): 636-638, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1886630

ABSTRACT

OBJECTIVE: To describe and explore the relationship between weather and the unusual 2020 bronchiolitis season in Western Australia during the COVID-19 pandemic. METHODS: Correlation of meteorological data and presentations of infants with bronchiolitis through the ED of Perth Children's Hospital. RESULTS: The 2020 bronchiolitis epidemic showed a reversal of the usual seasonal pattern. There were no weather events to account for this phenomenon. CONCLUSIONS: The bronchiolitis outbreak showed no relationship to local weather patterns. State-mandated COVID-19 public health measures appear as the likely rationale.


Subject(s)
Bronchiolitis , COVID-19 , Respiratory Syncytial Virus Infections , Bronchiolitis/epidemiology , COVID-19/epidemiology , Child , Humans , Infant , Pandemics , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Viruses , Seasons , Western Australia/epidemiology
4.
J Infect Dev Ctries ; 16(5): 857-863, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1879506

ABSTRACT

INTRODUCTION: Viruses are responsible for two-thirds of all acute respiratory tract infections. This study aims to retrospectively detect respiratory tract viruses in patients from all age groups who visited the hospital. METHODOLOGY: A total of 1592 samples from 1416 patients with respiratory tract symptoms were sent from several clinics to the Molecular Microbiology Laboratory at Gazi University Hospital from February 2016 to January 2019. Nucleic acid extraction from nasopharyngeal swabs, throat swabs or bronchoalveolar lavage (BAL) samples sent to our laboratory was done using a commercial automated system. Extracted nucleic acids were amplified by a commercial multiplex-real time Polymerase Chain Reaction (PCR) method, which can detect 18 viral respiratory pathogens. RESULTS: Among 1592 samples, 914 (57.4%) were positive for respiratory viruses. The most prevalent were rhinovirus (25.2%) and influenza A virus (12.1%), the least prevalent was the bocavirus (2.6%). Rhinovirus was the most detected as a single agent (21.2%, 194/914) among all positive cases, followed by coronavirus (9.3%, 85/914). The detection rates of coronavirus, human adenovirus, respiratory syncytial virus A/B, human parainfluenza viruses, human metapneumovirus-A/B, human parechovirus, enterovirus and influenza B virus were 9.9%, 8%, 7.7%, 5%, 3.4%, 3.1%, 3%, and 2.8%, respectively. CONCLUSIONS: The most detected viral agents in our study were influenza A virus and rhinovirus. Laboratory diagnosis of respiratory viruses is helpful to prevent unnecessary antibiotic use and is essential in routine diagnostics for antiviral treatment. Multiplex Real-time PCR method is fast and useful for the diagnosis of viral respiratory infections.


Subject(s)
Coronavirus Infections , Enterovirus Infections , Influenza, Human , Picornaviridae Infections , Respiratory Tract Infections , Coronavirus , Coronavirus Infections/epidemiology , Enterovirus Infections/epidemiology , Hospitals, University , Humans , Influenza A virus , Influenza, Human/epidemiology , Picornaviridae Infections/epidemiology , Respiratory Syncytial Viruses , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Retrospective Studies , Turkey/epidemiology
5.
Int J Environ Res Public Health ; 19(10)2022 05 13.
Article in English | MEDLINE | ID: covidwho-1855619

ABSTRACT

A descriptive analysis of common respiratory pathogens (CRPs) detected in nasopharyngeal swabs (NPSs) from hospitalized patients with influenza-like illness during the fall seasons of the past three years, 2019-2021, in the Lazio region, Italy, was conducted to assess whether or not CRP circulation changed because of COVID-19 during the fall season. The results observed in a total of 633 NPSs subjected to molecular diagnosis for CRPs by multiplex PCR assay during the autumn seasons (exactly from week 41 to week 50) were compared with each other. In 2019, in 144 NPSs, the more represented CRPs were rhinovirus/enterovirus (7.6%) and influenza A/B (4.2%). In 2020, 55 (21.6%) out of 255 NPSs resulted positive for SARS-CoV-2 and, except for one case of Legionella pneumophila, the CRPs detected were exclusively rhinovirus/enterovirus (4.7%). In 2021, among 234 NPSs, 25.6% resulted positive for SARS-CoV-2, 14.5% for respiratory syncytial virus (RSV), and 12.8% for rhinovirus/enterovirus. Compared with 2019, in 2020, CRP circulation was severely limited to a few cases; in 2021, instead, infections by RSV (detected also among adults), rhinovirus/enterovirus, and other respiratory pathogens were observed again, while influenza was practically absent. The comparison of the CRPs detected in the NPSs depicts a different circulation in the Lazio region during the last three fall seasons. CRP monitoring has a direct impact on the prevention and control strategies of respiratory infectious diseases, such as the non-pharmacological interventions implemented in response to the COVID-19 pandemic. Future studies should investigate the impact of specific interventions on the spread of respiratory infections.


Subject(s)
COVID-19 , Complex Regional Pain Syndromes , Influenza, Human , Virus Diseases , Viruses , Adult , COVID-19/epidemiology , Humans , Influenza, Human/epidemiology , Italy/epidemiology , Pandemics , Respiratory Syncytial Viruses , SARS-CoV-2 , Seasons , Virus Diseases/epidemiology
6.
J Clin Virol ; 150-151: 105164, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1851457

ABSTRACT

BACKGROUND: December 2021 witnessed an unprecedented increase in SARS-CoV-2 infections in addition to the circulation of influenza A and respiratory syncytial viruses (RSV). Due to increased testing demands for SARS-CoV-2, influenza, and RSV associated with the overall increase in symptomatic respiratory infections, there is an urgent need for multiplex, automated, and high throughput assays in the diagnostic laboratories. METHODS: We compared the performance of the NeuMoDx™ Flu A-B/RSV/SARS-CoV-2 Vantage and the Alinity m Resp-4-Plex to the standard of care influenza A, B, RSV, and SARS-CoV-2 assays used at the Johns Hopkins Microbiology Laboratory. A total of 181 remnant nasopharyngeal swab (NPS) specimens positive for influenza A (n = 29), influenza B (n = 34), RSV (n = 40), SARS-CoV-2 (n = 33), influenza A/RSV (n = 1), and negatives (n = 44) were tested by either or both assays. RESULTS: Both the NeuMoDx™ Flu A-B/RSV/SARS-CoV-2 Vantage and the Alinity m Resp-4-Plex assays showed 100% total agreement for all the tested analytes. For samples with available cycle threshold (Ct) values, comparable ranges were noted for all targets between the two assays and to the standard of care Ct values as well. CONCLUSION: The NeuMoDx™ Flu A-B/RSV/SARS-CoV-2 Vantage and the Alinity m Resp-4-Plex assays showed high sensitivity and accuracy for all the analytes included in both tests. Implementing these assays will assist the diagnostic laboratories with the surge of testing during the 2021-2022 influenza season.


Subject(s)
COVID-19 , Influenza, Human , Respiratory Syncytial Virus Infections , COVID-19/diagnosis , Humans , Influenza B virus , Influenza, Human/diagnosis , Nasopharynx , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Viruses , SARS-CoV-2 , Sensitivity and Specificity
7.
Emerg Microbes Infect ; 11(1): 1293-1307, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1788441

ABSTRACT

N-chlorotaurine (NCT) a long-lived oxidant generated by leukocytes, can be synthesized chemically and applied topically as an anti-infective to different body sites, including the lung via inhalation. Here, we demonstrate the activity of NCT against viruses causing acute respiratory tract infections, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza viruses, and respiratory syncytial virus (RSV). Virucidal activity of NCT was tested in plaque assays, confirmed by RT-qPCR assays. Attack on virus proteins was investigated by mass spectrometry. NCT revealed broad virucidal activity against all viruses tested at 37°C and pH 7. A significant reduction in infectious particles of SARS-CoV-2 isolates from early 2020 by 1 log10 was detected after 15 min of incubation in 1% NCT. Proteinaceous material simulating body fluids enhanced this activity by transchlorination mechanisms (1 -2 log10 reduction within 1-10 min). Tested SARS-CoV-2 variants B.1.1.7 (Alpha) und B.1.351 (Beta) showed a similar susceptibility. Influenza virus infectious particles were reduced by 3 log10 (H3N2) to 5 log10 (H1N1pdm), RSV by 4 log10 within a few min. Mass spectrometry of NCT-treated SARS-CoV-2 spike protein and 3C-like protease, influenza virus haemagglutinin and neuraminidase, and RSV fusion glycoprotein disclosed multiple sites of chlorination and oxidation as the molecular mechanism of action. Application of 1.0% NCT as a prophylactic and therapeutic strategy against acute viral respiratory tract infections deserves comprehensive clinical investigation.


Subject(s)
COVID-19 , Respiratory Tract Infections , COVID-19/drug therapy , Humans , Influenza A Virus, H3N2 Subtype , Respiratory Syncytial Viruses , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Taurine/analogs & derivatives
8.
Front Immunol ; 13: 853009, 2022.
Article in English | MEDLINE | ID: covidwho-1775683

ABSTRACT

Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, the current concept of pregnancy as a state of systemic immunosuppression seems oversimplified and outdated. Undoubtedly, in pregnancy the maternal immune system undergoes complex changes to establish and maintain tolerance to the fetus while still protecting from pathogens. In addition to downregulated maternal immunity, hormonal changes, and mechanical adaptation (e.g., restricted lung expansion) make the pregnant woman more susceptible to respiratory pathogens, such as influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Depending on the infectious agent and timing of the infection during gestation, fetal pathology can range from mild to severe, and even fatal. Influenza is associated with a higher risk of morbidity and mortality in pregnant women than in the general population, and, especially during the third trimester of pregnancy, mothers are at increased risk of hospitalization for acute cardiopulmonary illness, while their babies show higher risk of complications such as prematurity, respiratory and neurological illness, congenital anomalies, and admission to neonatal intensive care. RSV exposure in utero is associated with selective immune deficit, remodeling of cholinergic innervation in the developing respiratory tract, and abnormal airway smooth muscle contractility, which may predispose to postnatal airway inflammation and hyperreactivity, as well as development of chronic airway dysfunction in childhood. Although there is still limited evidence supporting the occurrence of vertical transmission of SARS-CoV-2, the high prevalence of prematurity among pregnant women infected by SARS-CoV-2 suggests this virus may alter immune responses at the maternal-fetal interface, affecting both the mother and her fetus. This review aims at summarizing the current evidence about the short- and long-term consequences of intrauterine exposure to influenza, RSV, and SARS-CoV-2 in terms of neonatal and pediatric outcomes.


Subject(s)
COVID-19 , Influenza, Human , Pregnancy Complications, Infectious , Child , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , Respiratory Syncytial Viruses , SARS-CoV-2
10.
Microbiol Spectr ; 10(1): e0109021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1673362

ABSTRACT

The rapid emergence of the coronavirus disease 2019 (COVID-19) pandemic has introduced a new challenge in diagnosing and differentiating respiratory infections. Accurate diagnosis of respiratory infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is complicated by overlapping symptomology, and stepwise approaches to testing for each infection would lead to increased reagent usage and cost, as well as delays in clinical interventions. To avoid these issues, multiplex molecular assays have been developed to differentiate between respiratory viruses in a single test to meet clinical diagnostic needs. To evaluate the analytical performance of the FDA emergency use authorization (EUA)-approved Abbott Alinity m resp-4-plex assay (Alinity m) in testing for SARS-CoV-2, influenza A virus, influenza B virus, and respiratory syncytial virus (RSV), we compared its performance to those of both the EUA-approved Cepheid Xpert Xpress SARS-CoV-2, influenza A/B virus, and RSV assay (Xpert Xpress) and the EUA-approved Roche Cobas SARS-CoV-2 and influenza A/B virus assay (Cobas) in a single-center retrospective analysis. High concordance was observed among all three assays, with kappa statistics showing an almost perfect agreement (>0.90). The limit of detection (LOD) results for SARS-CoV-2 showed the Alinity m exhibiting the lowest LOD at 26 copies/mL, followed by the Cobas at 58 copies/mL and the Xpert Xpress at 83 copies/mL, with LOD results for the influenza A virus, influenza B virus, and RSV viral targets also showing equivalent or better performance on the Alinity m compared to the other two platforms. The Alinity m can be used as a high-volume testing platform for SARS-CoV-2, influenza A virus, influenza B virus, and RSV and exhibits analytical performance comparable to those of both the Xpert Xpress and Cobas assays. IMPORTANCE The rapid emergence of SARS-CoV-2 has introduced a new challenge in diagnosing and differentiating respiratory infections, especially considering the overlapping symptomology of many of these infections and differences in clinical interventions depending on the pathogen identified. To avoid these issues, multiplex molecular assays like the one described in this article need to be developed to differentiate between the most common respiratory pathogens in a single test and most effectively meet clinical diagnostic needs.


Subject(s)
Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Respiratory Syncytial Viruses/isolation & purification , Respiratory Tract Infections/diagnosis , SARS-CoV-2/isolation & purification , Diagnosis, Differential , Humans , Respiratory Tract Infections/virology , Sensitivity and Specificity , Time Factors
11.
Chem Biodivers ; 19(1): e202100668, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1611203

ABSTRACT

Forsyqinlingines C (1) and D (2), two C9 -monoterpenoid alkaloids bearing a rare skeleton, were isolated from the ripe fruits of Forsythia suspensa. Their structures, including absolute configurations, were fully elucidated by extensive spectroscopic data and ECD experiments. The plausible biogenetic pathway for compounds 1 and 2 was also proposed. In vitro, two C9 -monoterpenoid alkaloids showed anti-inflammatory activity performed by the inhibitory effect on the release of ß-glucuronidase in rat polymorphonuclear leukocytes (PMNs), as well as antiviral activity against influenza A (H1N1) virus and respiratory syncytial virus (RSV).


Subject(s)
Alkaloids/chemistry , Anti-Inflammatory Agents/chemistry , Antiviral Agents/chemistry , Forsythia/chemistry , Monoterpenes/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Forsythia/metabolism , Fruit/chemistry , Fruit/metabolism , Glucuronidase/metabolism , Influenza A Virus, H1N1 Subtype/drug effects , Magnetic Resonance Spectroscopy , Molecular Conformation , Neutrophils/cytology , Neutrophils/drug effects , Neutrophils/metabolism , Platelet Activating Factor/pharmacology , Rats , Respiratory Syncytial Viruses/drug effects
13.
Rev Med Virol ; 31(6): e2234, 2021 11.
Article in English | MEDLINE | ID: covidwho-1574124

ABSTRACT

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Genetic Predisposition to Disease , Influenza, Human/immunology , Respiratory Syncytial Virus Infections/immunology , Severe Acute Respiratory Syndrome/immunology , Antiviral Agents/therapeutic use , Biological Variation, Individual , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/virology , Gene Expression , Humans , Immunity, Innate , Immunologic Factors/therapeutic use , Influenza, Human/drug therapy , Influenza, Human/genetics , Influenza, Human/virology , Mannose-Binding Lectin/genetics , Mannose-Binding Lectin/immunology , Orthomyxoviridae/drug effects , Orthomyxoviridae/immunology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/drug effects , Respiratory Syncytial Viruses/immunology , SARS Virus/drug effects , SARS Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology
14.
Aging (Albany NY) ; 13(23): 24931-24942, 2021 12 12.
Article in English | MEDLINE | ID: covidwho-1573020

ABSTRACT

Since the Coronavirus 19 (COVID-19) pandemic, several SARS-CoV-2 variants of concern (SARS-CoV-2 VOC) have been reported. The B.1.1.7 variant has been associated with increased mortality and transmission risk. Furthermore, cluster and possible co-infection cases could occur in the next influenza season or COVID-19 pandemic wave, warranting efficient diagnosis and treatment decision making. Here, we aimed to detect SARS-CoV-2 and other common respiratory viruses using multiplex RT-PCR developed on the LabTurbo AIO 48 open system. We performed a multicenter study to evaluate the performance and analytical sensitivity of the LabTurbo AIO 48 system for SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV) using 652 nasopharyngeal swab clinical samples from patients. The LabTurbo AIO 48 system demonstrated a sensitivity of 9.4 copies/per PCR for N2 of SARS-CoV-2; 24 copies/per PCR for M of influenza A and B; and 24 copies/per PCR for N of RSV. The assay presented consistent performance in the multicenter study. The multiplex RT-PCR applied on the LabTurbo AIO 48 open platform provided highly sensitive, robust, and accurate results and enabled high-throughput detection of B.1.1.7, influenza A/B, and RSV with short turnaround times. Therefore, this automated molecular diagnostic assay could enable streamlined testing if COVID-19 becomes a seasonal disease.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Influenza, Human/diagnosis , Multiplex Polymerase Chain Reaction/methods , Respiratory Syncytial Virus Infections/diagnosis , Adult , Aged , COVID-19/virology , Female , Humans , Influenza A virus/genetics , Influenza A virus/isolation & purification , Influenza, Human/virology , Influenzavirus B/genetics , Influenzavirus B/isolation & purification , Male , Middle Aged , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Viruses/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Young Adult
15.
PLoS One ; 16(11): e0258798, 2021.
Article in English | MEDLINE | ID: covidwho-1515477

ABSTRACT

Two main mechanisms contribute to the continuous evolution of influenza viruses: accumulation of mutations in the hemagglutinin and neuraminidase genes (antigenic drift) and genetic re-assortments (antigenic shift). Epidemiological surveillance is important in identifying new genetic variants of influenza viruses with potentially increased pathogenicity and transmissibility. In order to characterize the 2019/20 influenza epidemic in Romania, 1042 respiratory samples were collected from consecutive patients hospitalized with acute respiratory infections in the National Institute for Infectious Diseases "Prof. Dr. Matei Balș", Bucharest Romania and tested for influenza A virus, influenza B virus and respiratory syncytial virus (RSV) by real-time PCR. Out of them, 516 cases were positive for influenza, with relatively equal distribution of influenza A and B. Two patients had influenza A and B co-infection and 8 patients had influenza-RSV co-infection. The most severe cases, requiring supplemental oxygen administration or intensive care, and the most deaths were reported in patients aged 65 years and over. Subtyping showed the predominance of A(H3N2) compared to A(H1N1)pdm09 pdm09 (60.4% and 39.6% of all subtyped influenza A isolates, respectively), and the circulation of Victoria B lineage only. Influenza B started to circulate first (week 47/2019), with influenza A appearing slightly later (week 50/2019), followed by continued co-circulation of A and B viruses throughout the season. Sixty-eight samples, selected to cover the entire influenza season and all circulating viral types, were analysed by next generation sequencing (NGS). All A(H1N1)pdm09 sequences identified during this season in Romania were clustered in the 6b1.A clade (sub-clades: 6b1.A.183P -5a and 6b1.A.187A). For most A(H1N1)pdm09 sequences, the dominant epitope was Sb (pepitope = 0.25), reducing the vaccine efficacy by approximately 60%. According to phylogenetic analysis, influenza A(H3N2) strains circulating in this season belonged predominantly to clade 3C.3A, with only few sequences in clade 3C.2A1b. These 3C.2A1b sequences, two of which belonged to vaccinated patients, harbored mutations in antigenic sites leading to potential reduction of vaccine efficacy. Phylogenetic analysis of influenza B, lineage Victoria, sequences showed that the circulating strains belonged to clade V1A3. As compared to the other viral types, fewer mutations were observed in B/Victoria strains, with limited impact on vaccine efficiency based on estimations.


Subject(s)
Epidemics , Hospitalization , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H3N2 Subtype/genetics , Influenza B virus/genetics , Influenza, Human/epidemiology , Influenza, Human/history , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/history , Respiratory Syncytial Viruses/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Coinfection , Female , History, 21st Century , Humans , Infant , Infant, Newborn , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Influenza, Human/virology , Male , Middle Aged , Phylogeny , RNA, Viral/genetics , Respiratory Syncytial Virus Infections/virology , Romania/epidemiology , Young Adult
16.
Cells ; 10(11)2021 11 07.
Article in English | MEDLINE | ID: covidwho-1512135

ABSTRACT

The bronchial vascular endothelial network plays important roles in pulmonary pathology during respiratory viral infections, including respiratory syncytial virus (RSV), influenza A(H1N1) and importantly SARS-Cov-2. All of these infections can be severe and even lethal in patients with underlying risk factors.A major obstacle in disease prevention is the lack of appropriate efficacious vaccine(s) due to continuous changes in the encoding capacity of the viral genome, exuberant responsiveness of the host immune system and lack of effective antiviral drugs. Current management of these severe respiratory viral infections is limited to supportive clinical care. The primary cause of morbidity and mortality is respiratory failure, partially due to endothelial pulmonary complications, including edema. The latter is induced by the loss of alveolar epithelium integrity and by pathological changes in the endothelial vascular network that regulates blood flow, blood fluidity, exchange of fluids, electrolytes, various macromolecules and responses to signals triggered by oxygenation, and controls trafficking of leukocyte immune cells. This overview outlines the latest understanding of the implications of pulmonary vascular endothelium involvement in respiratory distress syndrome secondary to viral infections. In addition, the roles of infection-induced cytokines, growth factors, and epigenetic reprogramming in endothelial permeability, as well as emerging treatment options to decrease disease burden, are discussed.


Subject(s)
Endothelial Cells/pathology , Oxidative Stress , Respiratory Distress Syndrome/pathology , Virus Diseases/pathology , Epigenesis, Genetic , Humans , Influenza A Virus, H1N1 Subtype/physiology , Pulmonary Edema/genetics , Pulmonary Edema/pathology , Pulmonary Edema/virology , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/virology , Respiratory Syncytial Viruses/pathogenicity , SARS-CoV-2/pathogenicity , Virus Diseases/genetics , Virus Diseases/virology
17.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1501860

ABSTRACT

SARS-CoV-2 promotes an imbalanced host response that underlies the development and severity of COVID-19. Infections with viruses are known to modulate transposable elements (TEs), which can exert downstream effects by modulating host gene expression, innate immune sensing, or activities encoded by their protein products. We investigated the impact of SARS-CoV-2 infection on TE expression using RNA-Seq data from cell lines and from primary patient samples. Using a bioinformatics tool, Telescope, we showed that SARS-CoV-2 infection led to upregulation or downregulation of TE transcripts, a subset of which differed from cells infected with SARS, Middle East respiratory syndrome coronavirus (MERS-CoV or MERS), influenza A virus (IAV), respiratory syncytial virus (RSV), and human parainfluenza virus type 3 (HPIV3). Differential expression of key retroelements specifically identified distinct virus families, such as Coronaviridae, with unique retroelement expression subdividing viral species. Analysis of ChIP-Seq data showed that TEs differentially expressed in SARS-CoV-2 infection were enriched for binding sites for transcription factors involved in immune responses and for pioneer transcription factors. In samples from patients with COVID-19, there was significant TE overexpression in bronchoalveolar lavage fluid and downregulation in PBMCs. Thus, although the host gene transcriptome is altered by infection with SARS-CoV-2, the retrotranscriptome may contain the most distinctive features of the cellular response to SARS-CoV-2 infection.


Subject(s)
COVID-19/genetics , Endogenous Retroviruses/genetics , Long Interspersed Nucleotide Elements/genetics , A549 Cells , Cell Line , Chromatin Immunoprecipitation Sequencing , Computational Biology , Coronavirus Infections/genetics , DNA Transposable Elements/genetics , Down-Regulation , Host Microbial Interactions/genetics , Humans , In Vitro Techniques , Influenza A virus , Influenza, Human/genetics , Middle East Respiratory Syndrome Coronavirus , Parainfluenza Virus 3, Human , RNA-Seq , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Viruses , Respirovirus Infections/genetics , Retroelements/genetics , SARS Virus , SARS-CoV-2 , Severe Acute Respiratory Syndrome/genetics , Transcriptome , Up-Regulation
18.
Am J Respir Cell Mol Biol ; 66(2): 206-222, 2022 02.
Article in English | MEDLINE | ID: covidwho-1501858

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it with the host response to respiratory syncytial virus (RSV) and influenza virus. We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with influenza virus, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an IFN response in the nasal mucosa. The magnitude of the IFN response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2-infected adults had increased expression of genes involved in neutrophil activation and T-cell receptor signaling pathways compared with SARS-CoV-2-infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness.


Subject(s)
Aging/immunology , COVID-19/immunology , Gene Expression Regulation/immunology , Immunity, Mucosal , Nasal Mucosa/immunology , SARS-CoV-2/immunology , Adolescent , Age Factors , Angiotensin-Converting Enzyme 2/immunology , Child , Child, Preschool , Female , Humans , Infant , Male , Nasal Mucosa/virology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Viruses/immunology , Serine Endopeptidases/immunology
19.
Viruses ; 13(10)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1469382

ABSTRACT

Respiratory viruses are known to be the most frequent causative mediators of lung infections in humans, bearing significant impact on the host cell signaling machinery due to their host-dependency for efficient replication. Certain cellular functions are actively induced by respiratory viruses for their own benefit. This includes metabolic pathways such as glycolysis, fatty acid synthesis (FAS) and the tricarboxylic acid (TCA) cycle, among others, which are modified during viral infections. Here, we summarize the current knowledge of metabolic pathway modifications mediated by the acute respiratory viruses respiratory syncytial virus (RSV), rhinovirus (RV), influenza virus (IV), parainfluenza virus (PIV), coronavirus (CoV) and adenovirus (AdV), and highlight potential targets and compounds for therapeutic approaches.


Subject(s)
Citric Acid Cycle/physiology , Energy Metabolism/physiology , Fatty Acids/biosynthesis , Glycolysis/physiology , Respiratory Tract Infections/pathology , Respiratory Tract Infections/virology , Adenoviridae/metabolism , Coronavirus/metabolism , Humans , Orthomyxoviridae/metabolism , Parainfluenza Virus 1, Human/metabolism , Respiratory Syncytial Viruses/metabolism , Rhinovirus/metabolism
20.
Virol J ; 18(1): 202, 2021 10 09.
Article in English | MEDLINE | ID: covidwho-1463255

ABSTRACT

BACKGROUND: The effect of SARS-CoV-2 on existing respiratory pathogens in circulation remains uncertain. This study aimed to assess the impact of SARS-CoV-2 on the prevalence of respiratory pathogens among hospitalized children. METHODS: This study enrolled hospitalized children with acute respiratory infections in Shenzhen Children's Hospital from September to December 2019 (before the COVID-19 epidemic) and those from September to December 2020 (during the COVID-19 epidemic). Nasopharyngeal swabs were collected, and respiratory pathogens were detected using multiplex PCR. The absolute case number and detection rates of 11 pathogens were collected and analyzed. RESULTS: A total of 5696 children with respiratory tract infection received multiplex PCR examination for respiratory pathogens: 2298 from September to December 2019 and 3398 from September to December 2020. At least one pathogen was detected in 1850 (80.5%) patients in 2019, and in 2380 (70.0%) patients in 2020; the detection rate in 2020 was significantly lower than that in 2019.The Influenza A (InfA) detection rate was 5.6% in 2019, but 0% in 2020. The detection rates of Mycoplasma pneumoniae, Human adenovirus, and Human rhinovirus also decreased from 20% (460), 8.9% (206), and 41.8% (961) in 2019 to 1.0% (37), 2.1% (77), and 25.6% (873) in 2020, respectively. In contrast, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased from 6.6% (153), 9.9% (229), and 0.5% (12) in 2019 to 25.6% (873), 15.5% (530), and 7.2% (247) in 2020, respectively (p < 0.0001). CONCLUSIONS: Successful containment of seasonal influenza as a result of COVID-19 control measures will ensure we are better equipped to deal with future outbreaks of both influenza and COVID-19.Caused by virus competition, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased in Shenzhen,that reminds us we need to take further monitoring and preventive measures in the next epidemic season.


Subject(s)
Antibiosis , COVID-19/epidemiology , Respiratory Tract Diseases/epidemiology , SARS-CoV-2/isolation & purification , Adenoviruses, Human/genetics , Adenoviruses, Human/isolation & purification , Adolescent , COVID-19/virology , Child , Child, Hospitalized , Child, Preschool , China , Enterovirus/genetics , Enterovirus/isolation & purification , Female , Humans , Infant , Influenza A virus/genetics , Influenza A virus/isolation & purification , Male , Metapneumovirus/genetics , Metapneumovirus/isolation & purification , Mycoplasma pneumoniae/genetics , Mycoplasma pneumoniae/isolation & purification , Nasopharynx/microbiology , Nasopharynx/virology , Prevalence , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Viruses/isolation & purification , Respiratory Tract Diseases/microbiology , Respiratory Tract Diseases/virology , Respirovirus/genetics , Respirovirus/isolation & purification , SARS-CoV-2/genetics
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