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Science (New York, N.Y.) Aug 2020Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune...
Viral infections of the lower respiratory tract are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. In this study, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report that IFN-λ is present in the lower, but not upper, airways of patients with coronavirus disease 2019 (COVID-19). In mice, we demonstrate that IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-λ and its possible use in clinical practice against endemic viruses, such as influenza virus as well as the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Topics: Animals; Betacoronavirus; Bronchoalveolar Lavage Fluid; COVID-19; Cell Proliferation; Coronavirus Infections; Cytokines; Dendritic Cells; Humans; Interferon Type I; Interferons; Lung; Mice; Mice, Inbred C57BL; Nasopharynx; Pandemics; Pneumonia, Viral; Poly I-C; Respiratory Mucosa; SARS-CoV-2; Signal Transduction; Staphylococcal Infections; Superinfection; Toll-Like Receptor 3; Interferon Lambda
PubMed: 32527925
DOI: 10.1126/science.abc3545 -
Journal of Virology Jan 2023Globalization and climate change have contributed to the simultaneous increase and spread of arboviral diseases. Cocirculation of several arboviruses in the same...
Globalization and climate change have contributed to the simultaneous increase and spread of arboviral diseases. Cocirculation of several arboviruses in the same geographic region provides an impetus to study the impacts of multiple concurrent infections within an individual vector mosquito. Here, we describe coinfection and superinfection with the Mayaro virus (Togaviridae, ) and Zika virus (Flaviviridae, ) in vertebrate and mosquito cells, as well as Aedes aegypti adult mosquitoes, to understand the interaction dynamics of these pathogens and effects on viral infection, dissemination, and transmission. Aedes aegypti mosquitoes were able to be infected with and transmit both pathogens simultaneously. However, whereas Mayaro virus was largely unaffected by coinfection, it had a negative impact on infection and dissemination rates for Zika virus compared to single infection scenarios. Superinfection of Mayaro virus atop a previous Zika virus infection resulted in increased Mayaro virus infection rates. At the cellular level, we found that mosquito and vertebrate cells were also capable of being simultaneously infected with both pathogens. Similar to our findings , Mayaro virus negatively affected Zika virus replication in vertebrate cells, displaying complete blocking under certain conditions. Viral interference did not occur in mosquito cells. Epidemiological and clinical studies indicate that multiple arboviruses are cocirculating in human populations, leading to some individuals carrying more than one arbovirus at the same time. In turn, mosquitoes can become infected with multiple pathogens simultaneously (coinfection) or sequentially (superinfection). Coinfection and superinfection can have synergistic, neutral, or antagonistic effects on viral infection dynamics and ultimately have impacts on human health. Here we investigate the interaction between Zika virus and Mayaro virus, two emerging mosquito-borne pathogens currently circulating together in Latin America and the Caribbean. We find a major mosquito vector of these viruses-Aedes aegypti-can carry and transmit both arboviruses at the same time. Our findings emphasize the importance of considering co- and superinfection dynamics during vector-pathogen interaction studies, surveillance programs, and risk assessment efforts in epidemic areas.
Topics: Animals; Humans; Aedes; Alphavirus; Alphavirus Infections; Coinfection; Mosquito Vectors; Superinfection; Vertebrates; Zika Virus; Zika Virus Infection
PubMed: 36598200
DOI: 10.1128/jvi.01778-22 -
Deutsches Arzteblatt International Aug 2022
Topics: Humans; Papilloma; Skin
PubMed: 36384928
DOI: 10.3238/arztebl.m2022.0088 -
Viruses Sep 2023The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear....
BACKGROUND
The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients.
METHODS
Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant was assessed.
RESULTS
The incidence of KPC-producing and/or carbapenem-resistant rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing and/or carbapenem-resistant occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24-1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18-12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43-9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40-0.72) were the features most strongly associated with in-hospital mortality.
CONCLUSIONS
Although KPC-producing and/or carbapenem-resistant rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.
Topics: Adult; Humans; Carbapenems; Anti-Bacterial Agents; Retrospective Studies; Prevalence; Superinfection; COVID-19; SARS-CoV-2; Klebsiella pneumoniae; Sepsis
PubMed: 37766340
DOI: 10.3390/v15091934 -
The Journal of Infectious Diseases Sep 2022Viral respiratory tract infections (VRTIs) are among the most common diseases, but the risks of superinfection for different virus species have never been compared.
BACKGROUND
Viral respiratory tract infections (VRTIs) are among the most common diseases, but the risks of superinfection for different virus species have never been compared.
METHODS
Multicenter retrospective study conducted among adults who tested positive for VRTIs with reverse-transcription polymerase chain reaction. We compared characteristics between influenza (A or B) and paramyxoviruses (respiratory syncytial virus, parainfluenza virus types 1 and 3, and human metapneumovirus) and identified predictors of superinfection and hospitalization.s.
RESULTS
Five hundred ninety patients had VRTI, including 347 (59%) influenza and 243 paramyxovirus infections with comparable rates of superinfections (53% vs 60%). In multivariate analyses, the predictors of superinfections were age >75 years (adjusted odds ratio, 2.37 [95% confidence interval, 1.65-3.40]), chronic respiratory disease (1.79 [1.20-2.67]), and biological abnormalities, including neutrophil count >7000/µL (1.98 [1.34-2.91)], eosinophil count <50/µL (2.53 [1.61-3.98], and procalcitonin level >0.25ng/mL (2.8 [1.65-4.73]). The predictors of hospitalization were age >75 years old (adjusted odds ratio, 3.49 [95% confidence interval, 2.17-5.63]), paramyxovirus infection (2.28 [1.39-3.75]), long-term use of inhaled corticosteroids (2.49 [1.13-5.49]), and biological abnormalities, including neutrophil count >7000/µL (2.38 [1.37-4.12)] and procalcitonin level >0.25ng/mL (2.49 [1.23-5.02]). Kaplan-Meier survival curves showed that influenza-infected patients had a higher mortality rate than those with paramyxovirus infections (8.9% vs 4.5%, respectively; P = .02).
CONCLUSIONS
Our study revealed a high rate of superinfection (56%), not related to viral species. However influenza virus was associated with a poorer prognosis than paramyxoviruses, pleading for a broader and large-scale vaccination of individual at risk of VRTIs.
Topics: Adult; Aged; Hospitalization; Humans; Influenza, Human; Paramyxoviridae Infections; Procalcitonin; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Superinfection
PubMed: 34636898
DOI: 10.1093/infdis/jiab525 -
Scandinavian Journal of Clinical and... Apr 2022In critical patients with Coronavirus Disease (COVID-19), we investigated the diagnostic value of presepsin in the early diagnosis of superinfection with sepsis, and the...
In critical patients with Coronavirus Disease (COVID-19), we investigated the diagnostic value of presepsin in the early diagnosis of superinfection with sepsis, and the effect of antibiotic treatment (AT) in the levels of presepsin and procalcitonin and C-reactive protein. A total of 68 critical patients with sepsis and septic shock in the intensive care unit and 20 outpatients (control group) with COVID-19 were taken. ICU patients ( = 68) were further divided into three groups. C(-)AT(-) had negative blood or tracheal aspirate cultures (C) and not AT on admission to ICU ( = 18), C(-)AT(+) had negative C and AT on admission to intensive care unit ( = 31) and C(+) had positive C ( = 19). Presepsin, procalcitonin, C-reactive protein results were compared between the groups. There were no significant relationships between presepsin levels with sepsis, septic shock, mortality, or length of stay in ICU in patients with COVID-19. For procalcitonin and C-reactive protein levels in C(-)AT(+) and C(+) groups were significantly higher than in control and C(-)AT(-) groups ( < .001). C-reactive protein levels in C(-)AT(-) group were significantly higher than in the control group ( < .001). PCT and CRP, there was no difference between C(-)AT(+) and C(+) groups, and procalcitonin there was no difference between control and C(-)AT(-) groups. Presepsin was not found as a useful biomarker for the prediction of sepsis in COVID-19 patients. These study findings indicate that procalcitonin and C-reactive protein may be an indicator of an early diagnostic marker for superinfection in critical COVID-19 patients.
Topics: Biomarkers; C-Reactive Protein; COVID-19; Early Diagnosis; Humans; Lipopolysaccharide Receptors; Peptide Fragments; Procalcitonin; Sepsis; Shock, Septic; Superinfection
PubMed: 35103516
DOI: 10.1080/00365513.2022.2031278 -
Journal of Oral Pathology & Medicine :... May 2023Oral candidiasis occasionally occurs in patients with oral lichen planus (OLP) or lichenoid reaction (OLR). However, not all patients undergoing corticosteroid therapy...
BACKGROUND
Oral candidiasis occasionally occurs in patients with oral lichen planus (OLP) or lichenoid reaction (OLR). However, not all patients undergoing corticosteroid therapy develop Candida superinfection. Thus, the identification of prognostic risk factors may help to identify patients at risk of Candida superinfection.
METHODS
A retrospective cohort study was conducted to review patients with OLP/OLR who received steroid therapy at a single dental hospital between January 2016 and December 2021. The prevalence of Candida superinfection and prognostic factors were assessed.
RESULTS
Eighty-two eligible patients with OLP/OLR were retrospectively reviewed. The overall prevalence of Candida superinfection during the study period was 35.37%; the median time-to-event between initiation of corticosteroid therapy and diagnosis of superinfection was 60 days (interquartile range; 34-296). The ulcerative type of OLP/OLR, number of topical steroid applications, poor oral hygiene, and oral dryness were significantly associated with superinfection (p < 0.05; Fisher's Exact test) and were identified as prognostic factors in univariable risk ratio regression. Multivariable risk ratio regression revealed the ulcerative type of OLP/OLR and number of topical steroid applications were significant prognostic factors for Candida superinfection in patients with OLP/OLR.
CONCLUSION
Candida superinfection occurs in approximately one-third of patients with OLP/OLR undergoing corticosteroid therapy. Patients with OLP/OLR should be closely monitored in the first 2 months (60 days; median time to infection) after steroid prescription. The ulcerative type of OLP/OLR and a higher number of topical steroid applications per day may represent prognostic factors to identify patients at risk of Candida superinfection.
Topics: Humans; Lichen Planus, Oral; Retrospective Studies; Candida; Prevalence; Prognosis; Superinfection; Steroids; Lichenoid Eruptions; Adrenal Cortex Hormones
PubMed: 36912778
DOI: 10.1111/jop.13420 -
Journal of Clinical Medicine Mar 2022The SARS-CoV-2 pandemic might have increased the risks of healthcare-associated infections (HAIs); however, several studies of HAI such as urinary tract infections...
The SARS-CoV-2 pandemic might have increased the risks of healthcare-associated infections (HAIs); however, several studies of HAI such as urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs) have shown contradictory results. The aim of this study is to assess the clinical features of UTIs and bacterial isolates from urine samples of hospitalized COVID-19 patients. We conducted a retrospective observational study including 87 COVID-19 patients with UTIs admitted to our centre. Bacterial UTIs presented were 87: 9 (10.3%) community-acquired UTIs (coinfection group) and 78 (89.6%) hospital-acquired UTIs (superinfection group). In the coinfection group, the most frequent type was non-CAUTI with 5 (55.5%) patients; however, the most frequent UTI in the superinfection group was CAUTI, with 53 (67.9%) patients. The median number of days of hospitalization in coinfected patients was lower than superinfection patients: 13 (IQR 11, 23) vs. 34 days (IQR 23, 47) p < 0.006. All UTI patients admitted to ICU, 38 (43.7%), belonged to the superinfection group. The mortality rate was 26.4% (23/87), 22/23 in the superinfection group. The most common microorganisms were E. coli 27 (28.4%), E. faecalis 25 (26.3%) and E. faecium 20 (21.1%). There was an increased incidence of E. faecalis and E. faecium in UTIs as well as hospital-acquired UTIs. This can be related to urethral catheterization during hospitalization, UCI admissions and the number of days of hospitalization.
PubMed: 35407423
DOI: 10.3390/jcm11071815 -
BioRxiv : the Preprint Server For... Aug 2023Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems...
Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the (repressor), , , and genes. Here we report that the P22-encoded SieA protein is the only phage protein required for exclusion by the SieA system, and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants were isolated that overcome the SieA block, and they have amino acid changes in the C-terminal regions of the gene and encoded ejection proteins. Three different single amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in target specificity. Our data are consistent with a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.
PubMed: 37645741
DOI: 10.1101/2023.08.15.553423 -
MBio Feb 2024Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems...
Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the (repressor), , , and genes. Here we report that the P22-encoded SieA protein is necessary and sufficient for exclusion by the SieA system and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants that overcome the SieA block were isolated, and they have amino acid changes in the C-terminal regions of the gene and encoded ejection proteins. Three different single-amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in phage target specificity. Our data strongly suggest a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.IMPORTANCEThe ongoing evolutionary battle between bacteria and the viruses that infect them is a critical feature of bacterial ecology on Earth. Viruses can kill bacteria by infecting them. However, when their chromosomes are integrated into a bacterial genome as a prophage, viruses can also protect the host bacterium by expressing genes whose products defend against infection by other viruses. This defense property is called "superinfection exclusion." A significant fraction of bacteria harbor prophages that encode such protective systems, and there are many different molecular strategies by which superinfection exclusion is mediated. This report is the first to describe the mechanism by which bacteriophage P22 SieA superinfection exclusion protein protects its host bacterium from infection by other P22-like phages. The P22 prophage-encoded inner membrane SieA protein prevents infection by blocking transport of superinfecting phage DNA across the inner membrane during injection.
Topics: Humans; Bacteriophage P22; Superinfection; Bacteriophages; Prophages; Membrane Proteins; DNA; Amino Acids
PubMed: 38236051
DOI: 10.1128/mbio.02169-23