scholarly journals Allergic inflammation hinders synergistic viral-bacterial co-infection in C57BL/6 mice

2019 ◽  
Author(s):  
Kim S. LeMessurier ◽  
Amy R. Iverson ◽  
Ti-Cheng Chang ◽  
Maneesha Palipane ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Lung Disease ◽  
Influenza A ◽  
Respiratory Infections ◽  
Negative Impact ◽  
Influenza Pandemic ◽  
Severe Disease ◽  
Allergic Inflammation ◽  
Lung Microbiome ◽  
Severe Influenza ◽  
The Impact

AbstractAsthma is a chronic airways disease that can be exacerbated during respiratory infections. Our previous findings that the inflammatory state of allergic airways at the time of influenza A virus (IAV) infection in combination with epidemiologic findings that asthmatics were less likely to suffer from severe influenza during the 2009 pandemic suggest that additional complications of influenza, such as increased susceptibility to bacterial superinfection, may be mitigated in the allergic host. To test this hypothesis, we developed a murine model of ‘triple-disease’ in which mice were first rendered allergic to Aspergillus fumigatus and co-infected with IAV and Streptococcus pneumoniae seven days apart. Significant alterations to known synergistic effects of co-infection were noted in the allergic mice including reduced morbidity and mortality, bacterial burden, maintenance of alveolar macrophages, and reduced lung inflammation and damage. The lung microbiome of allergic mice differed from that of non-allergic mice during co-infection. To investigate the impact of the microbiome on the pathogenesis of lung disease, we induced a perturbation with a short course of fluoroquinolone antibiotic that is often prescribed for lung infections. A significant change in the microbiome was complemented with alterations to the inflammatory profile and a drastic increase in pro-inflammatory cytokines in allergic mice which were now susceptible to severe disease from IAV and S. pneumoniae co-infection. Our data suggest that responses to co-infection in allergic hosts likely depends on the immune and microbiome states and that antibiotics should be used with caution in individuals with underlying chronic lung disease.Author SummaryAsthma is a condition of the lungs that affects millions worldwide. Traditionally, respiratory infections are considered to have a negative impact on asthmatics. However, epidemiological data surrounding the 2009 influenza pandemic suggest that asthmatics may be better equipped to counter severe influenza including bacterial pneumonia. Herein, we introduce a novel mouse model system designed to recapitulate an influenza virus and Streptococcal co-infection in a host with fungal asthma. We found that underlying allergic asthma protects against severe disease induced by co-infection. Mice with underlying allergic inflammation had reduced damage to the lungs and did not show signs of respiratory distress. Among the differences noted in the allergic mice that were protected from viral and bacterial co-infection, was the lung microbiome. Allergic mice lost their protection from co-infection after we perturbed their lung microbiome with antibiotics suggesting that the lung microbiome plays a role in host immunity against invading pathogens.

scholarly journals Allergic inflammation alters the lung microbiome and hinders synergistic co-infection with H1N1 influenza virus and Streptococcus pneumoniae in C57BL/6 mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kim S. LeMessurier ◽  
Amy R. Iverson ◽  
Ti-Cheng Chang ◽  
Maneesha Palipane ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Influenza A ◽  
Respiratory Infections ◽  
Synergistic Effects ◽  
Allergic Inflammation ◽  
H1n1 Influenza ◽  
H1n1 Influenza Virus ◽  
Lung Microbiome ◽  
Bacterial Superinfection ◽  
Increased Susceptibility

AbstractAsthma is a chronic airways condition that can be exacerbated during respiratory infections. Our previous work, together with epidemiologic findings that asthmatics were less likely to suffer from severe influenza during the 2009 pandemic, suggest that additional complications of influenza such as increased susceptibility to bacterial superinfection, may be mitigated in allergic hosts. To test this hypothesis, we developed a murine model of ‘triple-disease’ in which mice rendered allergic to Aspergillus fumigatus were co-infected with influenza A virus and Streptococcus pneumoniae seven days apart. Significant alterations to known synergistic effects of co-infection were noted in the allergic mice including reduced morbidity and mortality, bacterial burden, maintenance of alveolar macrophages, and reduced lung inflammation and damage. The lung microbiome of allergic mice differed from that of non-allergic mice during co-infection and antibiotic-induced perturbation to the microbiome rendered allergic animals susceptible to severe morbidity. Our data suggest that responses to co-infection in allergic hosts likely depends on the immune and microbiome states and that antibiotics should be used with caution in individuals with underlying chronic lung disease.

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

scholarly journals Characteristics of Critically Ill Patients with COVID-19 Compared to Patients with Influenza—A Single Center Experience

2021 ◽  
Vol 10 (10) ◽  
pp. 2056
Author(s):  
Frank Herbstreit ◽  
Marvin Overbeck ◽  
Marc Moritz Berger ◽  
Annabell Skarabis ◽  
Thorsten Brenner ◽  
...  
Keyword(s):  
Influenza A ◽  
Health Care Systems ◽  
Severe Disease ◽  
Tertiary Care ◽  
Care Facility ◽  
High Volume ◽  
Single Center Experience ◽  
Severe Influenza ◽  
Tertiary Care Facility ◽  
Care Systems

Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic (n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19.

scholarly journals Real-time estimation of the hospitalization fatality risk of influenza A(H1N1)pdm09 in Hong Kong

2015 ◽  
Vol 144 (8) ◽  
pp. 1579-1583
Author(s):  
J. Y. WONG ◽  
P. WU ◽  
E. H. Y. LAU ◽  
T. K. TSANG ◽  
V. J. FANG ◽  
...  
Keyword(s):  
Hong Kong ◽  
Real Time ◽  
Influenza A ◽  
Early Stage ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Right Censoring ◽  
Fatality Risk ◽  
Influenza A H1n1 ◽  
The Impact

SUMMARYDuring the early stage of an epidemic, timely and reliable estimation of the severity of infections are important for predicting the impact that the influenza viruses will have in the population. We obtained age-specific deaths and hospitalizations for patients with laboratory-confirmed H1N1pdm09 infections from June 2009 to December 2009 in Hong Kong. We retrospectively obtained the real-time estimates of the hospitalization fatality risk (HFR), using crude estimation or allowing for right-censoring for final status in some patients. Models accounting for right-censoring performed better than models without adjustments. The risk of deaths in hospitalized patients with confirmed H1N1pdm09 increased with age. Reliable estimates of the HFR could be obtained before the peak of the first wave of H1N1pdm09 in young and middle-aged adults but after the peak in the elderly. In the next influenza pandemic, timely estimation of the HFR will contribute to risk assessment and disease control.

scholarly journals Natural Variation Can Significantly Alter the Sensitivity of Influenza A (H5N1) Viruses to Oseltamivir

2006 ◽  
Vol 50 (11) ◽  
pp. 3809-3815 ◽  
Author(s):  
M. A. Rameix-Welti ◽  
F. Agou ◽  
P. Buchy ◽  
S. Mardy ◽  
J. T. Aubin ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Fold Increase ◽  
Influenza Viruses ◽  
Control Measures ◽  
Inhibition Assay ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
The Impact

ABSTRACT Geographic spread of highly pathogenic avian H5N1 influenza viruses may give rise to an influenza pandemic. During the first months of a pandemic, control measures would rely mainly on antiviral drugs, such as the neuraminidase (NA) inhibitors oseltamivir and zanamivir. In this study, we compare the sensitivities to oseltamivir of the NAs of several highly pathogenic H5N1 viruses isolated in Asia from 1997 to 2005. The corresponding 50% inhibitory concentrations were determined using a standard in vitro NA inhibition assay. The Km for the substrate and the affinity for the inhibitor (Ki ) of NA were determined for a 1997 and a 2005 virus, using an NA inhibition assay on cells transiently expressing the viral enzyme. Our data show that the sensitivities of the NAs of H5N1 viruses isolated in 2004 and 2005 to oseltamivir are about 10-fold higher than those of earlier H5N1 viruses or currently circulating H1N1 viruses. Three-dimensional modeling of the N1 protein predicted that Glu248Gly and Tyr252His changes could account for increased sensitivity. Our data indicate that genetic variation in the absence of any drug-selective pressure may result in significant variations in sensitivity to anti-NA drugs. Although the clinical relevance of a 10-fold increase in the sensitivity of NA to oseltamivir needs to be investigated further, the possibility that sensitivity to anti-NA drugs could increase (or possibly decrease) significantly, even in the absence of treatment, underscores the need for continuous evaluation of the impact of genetic drift on this parameter, especially for influenza viruses with pandemic potential.

scholarly journals Critical care surveillance: insights into the impact of the 2010/11 influenza season relative to the 2009/10 pandemic season in England

2013 ◽  
Vol 18 (23) ◽  
Author(s):  
H K Green ◽  
J Ellis ◽  
M Galiano ◽  
J M Watson ◽  
R G Pebody
Keyword(s):  
Critical Care ◽  
Influenza A ◽  
Influenza Season ◽  
Severe Disease ◽  
Vaccine Uptake ◽  
Cold Weather ◽  
Influenza B ◽  
Influenza A H1n1 ◽  
The Impact ◽  
Age Shift

In 2010/11, the influenza season in England was marked by a relative increase in impact on the population compared to that seen during the 2009/10 pandemic, with the same influenza subtype, A(H1N1)pdm09, circulating. The peaks in critical care bed occupancy in both seasons coincided with peaks in influenza A(H1N1)pdm09 activity, but onset of influenza in 2010/11 additionally coincided with notably cold weather, a comparatively smaller peak in influenza B activity and increased reports of bacterial co-infection. A bigger impact on critical care services was seen across all regions in England in 2010/11, with, compared to 2009/10, a notable age shift in critical care admissions from children to young adults. The peak of respiratory syncytial virus (RSV) activity did not coincide with critical care admissions, and regression analysis suggested only a small proportion of critical care bed days might be attributed to the virus in either season. Differences in antiviral policy and improved overall vaccine uptake in 2010/11 with an influenza A(H1N1)pdm09 strain containing vaccine between seasons are unlikely to explain the change in impact observed between the two seasons. The reasons behind the relative high level of severe disease in the 2010/11 winter are likely to have resulted from a combination of factors, including an age shift in infection, accumulation of susceptible individuals through waning immunity, new susceptible individuals from new births and cold weather. The importance of further development of severe influenza disease surveillance schemes for future seasons is reinforced.

scholarly journals BioFire FilmArray Decreases Infection Control Isolation Times by 4 days in ICU, BMT and Respiratory Wards

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S353-S353 ◽  
Author(s):  
Titus Wong ◽  
Aleksandra Stefanovic ◽  
Kerstin Locher ◽  
Elizabeth Bryce ◽  
Jennifer M Grant ◽  
...  
Keyword(s):  
Infection Control ◽  
Influenza A ◽  
Respiratory Infections ◽  
Tertiary Care ◽  
Diagnostic Testing ◽  
Cost Benefit ◽  
Respiratory Pathogen ◽  
Duration Of Infection ◽  
The Impact ◽  
Research Grant

Abstract Background Novel, rapid, syndromic testing of patients presenting with respiratory infections has the potential to improve patient access and care by decreasing time to diagnosis. BioFire FilmArray (BioFire Diagnostics, bioMerieux) is a cartridge-based, multiplex PCR platform capable of detecting 17 viral and 3 bacterial targets in one hour. This study assessed the impact of implementing this technology on the duration of infection control isolation. Methods A randomized control trial in a 900-bed tertiary-care academic hospital was conducted between December 2016 and January 2017. Fifty consecutive samples of patients with respiratory infections on our ICU, BMT and Respiratory wards to received either BioFire FilmArray Respiratory Panel (BF) diagnostic testing or our routine diagnostic testing (RO) consisting of an influenza A/B/RSV PCR (in-house) followed by Luminex NxTag Respiratory Pathogen Panel that was batched at a reference lab. Five patient charts with missing data were excluded from analysis. Statistical analysis was completed using RStudio Version 1.0.136 – © 2009–2016 RStudio, Inc. Results Patients randomized to the BF arm remained on respiratory isolation precautions on average (42.3 ± 72.9 hours) over 100 hours less than patients randomized to the routine arm (151.3 ± 151.8 hours) (95% CI: 35.6–184.4 hours, P = 0.0052). Conclusion Implementing the BioFire FilmArray Respiratory Panel decreased infection control isolation time by approximately 4 days compared with routine testing; further study is warranted to determine the impact of this technology on patient outcomes and cost benefit. Disclosures T. Wong, bioMerieux: Investigator, Research grant A. Stefanovic, bioMerieux: Investigator, Research grant E. Bryce, bioMerieux: Investigator, Research grant J. M. Grant, bioMerieux: Investigator, Research grant D. Roscoe, bioMerieux: Investigator, Research grant

scholarly journals Tuberculosis and COVID-19: Lessons from the Past Viral Outbreaks and Possible Future Outcomes

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Radu Crisan-Dabija ◽  
Cristina Grigorescu ◽  
Cristina-Alice Pavel ◽  
Bogdan Artene ◽  
Iolanda Valentina Popa ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Influenza Pandemic ◽  
Essential Elements ◽  
Diagnostic Reliability ◽  
Clinical Evolution ◽  
Link Type ◽  
Data Mining Approach ◽  
Future Outcomes ◽  
Viral Respiratory Infections ◽  
The Impact

Background. The threat of contagious infectious diseases is constantly evolving as demographic explosion, travel globalization, and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results. The PubMed electronic database was systematically searched for relevant articles linking TB, influenza, and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (focusing on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from past outbreaks (other coronaviruses) and influenza pandemic/seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions. Because viral respiratory infections and TB impede the host’s immune responses, it can be assumed that their lethal synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead. The trial is registered with NCT04327206, NCT01829490, and NCT04121494.

scholarly journals Influenza and Community-acquired Pneumonia Interactions: The Impact of Order and Time of Infection on Population Patterns

2012 ◽  
Vol 175 (5) ◽  
pp. 363-367 ◽  
Author(s):  
Brian M. Davis ◽  
Allison E. Aiello ◽  
Suzanne Dawid ◽  
Pejman Rohani ◽  
Sourya Shrestha ◽  
...  
Keyword(s):  
Influenza A ◽  
Animal Studies ◽  
Severe Disease ◽  
Severity Of Illness ◽  
Population Level ◽  
Community Acquired Pneumonia ◽  
Swine Flu ◽  
1918 Influenza ◽  
The Impact

AbstractDiscoveries made during the 1918 influenza A pandemic and reports of severe disease associated with coinfection during the 2009 hemagglutinin type 1 and neuraminidase type 1 (commonly known as H1N1 or swine flu) pandemic have renewed interest in the role of coinfection in disease pathogenesis. The authors assessed how various timings of coinfection with influenza virus and pneumonia-causing bacteria could affect the severity of illness at multiple levels of interaction, including the biologic and population levels. Animal studies most strongly support a single pathway of coinfection with influenza inoculation occurring approximately 7 days before inoculation with Streptococcus pneumoniae, but less-examined pathways of infection also may be important for human disease. The authors discussed the implications of each pathway for disease prevention and what they would expect to see at the population level if there were sufficient data available. Lastly, the authors identified crucial gaps in the study of timing of coinfection and proposed related research questions.

scholarly journals Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2

2021 ◽  
Author(s):  
Guoli Shi ◽  
Abhilash I Chiramel ◽  
Saliha Majdoul ◽  
Kin Kui Lai ◽  
Sudipto Das ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Functional Divergence ◽  
Severe Disease ◽  
Drug Repurposing ◽  
Mtor Inhibitors ◽  
Cell Entry ◽  
Viral Fusion ◽  
Human Respiratory Tract ◽  
The Impact

Infection by SARS-CoV-2 generally causes mild symptoms but can lead to severe disease and death in certain populations, including the immunocompromised. Drug repurposing efforts are underway to identify compounds that interfere with SARS-CoV-2 replication or the immunopathology it can elicit. Rapamycin is among those being currently tested in clinical trials for impacts on COVID-19 severity. While rapamycin and rapamycin analogs (rapalogs) are FDA-approved for use as mTOR inhibitors in multiple clinical settings, including cancer, we previously found that rapamycin can increase the susceptibility of cells to infection by Influenza A virus. In this study, we tested the impact of rapalogs on cellular susceptibility to SARS-CoV-2 infection. We report that rapamycin and rapalogs increased SARS-CoV-2 titers in human cervical epithelial and lung epithelial cell lines to different extents, and a similar pattern of enhancement was observed using pseudovirus incorporating viral fusion proteins from SARS-CoV-2, SARS-CoV, MERS, and Influenza A Virus. Rapalogs also promoted cell entry driven by SARS-CoV-2 Spike in nasal cells and primary small airway cells, representing proximal and distal ends of the human respiratory tract, respectively. Interestingly, cell entry enhancement by the rapalog ridaforolimus was cell type-dependent, revealing a previously unrecognized functional divergence between rapalogs. The differential activity of rapalogs was associated with their capacity to induce the degradation of interferon-inducible transmembrane (IFITM) proteins, restriction factors that broadly inhibit virus infection. Our findings will spur the development of mTOR inhibitors that do not suppress the first line of antiviral defense in cells.

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