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Journal of Clinical Medicine May 2023Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure defined by dysregulated immune homeostasis and alveolar epithelial and...
Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure defined by dysregulated immune homeostasis and alveolar epithelial and endothelial damage. Up to 40% of ARDS patients develop pulmonary superinfections, contributing to poor prognosis and increasing mortality. Understanding what renders ARDS patients highly susceptible to pulmonary superinfections is therefore essential. We hypothesized that ARDS patients who develop pulmonary superinfections display a distinct pulmonary injury and pro-inflammatory response pattern. Serum and BALF samples from 52 patients were collected simultaneously within 24 h of ARDS onset. The incidence of pulmonary superinfections was determined retrospectively, and the patients were classified accordingly. Serum concentrations of the epithelial markers soluble receptor for advanced glycation end-products (sRAGE) and surfactant protein D (SP-D) and the endothelial markers vascular endothelial growth factor (VEGF) and angiopoetin-2 (Ang-2) as well as bronchoalveolar lavage fluid concentrations of the pro-inflammatory cytokines interleukin 1ß (IL-1ß), interleukin 18 (IL-18), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-a) were analyzed via multiplex immunoassay. Inflammasome-regulated cytokine IL-18 and the epithelial damage markers SP-D and sRAGE were significantly increased in ARDS patients who developed pulmonary superinfections. In contrast, endothelial markers and inflammasome-independent cytokines did not differ between the groups. The current findings reveal a distinct biomarker pattern that indicates inflammasome activation and alveolar epithelial injury. This pattern may potentially be used in future studies to identify high-risk patients, enabling targeted preventive strategies and personalized treatment approaches.
PubMed: 37297845
DOI: 10.3390/jcm12113649 -
Open Forum Infectious Diseases Sep 2022Identification of bacterial coinfection in patients with coronavirus disease 2019 (COVID-19) facilitates appropriate initiation or withholding of antibiotics. The...
Detection of Viral Infection and Bacterial Coinfection and Superinfection in Coronavirus Disease 2019 Patients Presenting to the Emergency Department Using the 29-mRNA Host Response Classifier IMX-BVN-3: A Multicenter Study.
BACKGROUND
Identification of bacterial coinfection in patients with coronavirus disease 2019 (COVID-19) facilitates appropriate initiation or withholding of antibiotics. The Inflammatix Bacterial Viral Noninfected (IMX-BVN) classifier determines the likelihood of bacterial and viral infections. In a multicenter study, we investigated whether IMX-BVN version 3 (IMX-BVN-3) identifies patients with COVID-19 and bacterial coinfections or superinfections.
METHODS
Patients with polymerase chain reaction-confirmed COVID-19 were enrolled in Berlin, Germany; Basel, Switzerland; and Cleveland, Ohio upon emergency department or hospital admission. PAXgene Blood RNA was extracted and 29 host mRNAs were quantified. IMX-BVN-3 categorized patients into very unlikely, unlikely, possible, and very likely bacterial and viral interpretation bands. IMX-BVN-3 results were compared with clinically adjudicated infection status.
RESULTS
IMX-BVN-3 categorized 102 of 111 (91.9%) COVID-19 patients into very likely or possible, 7 (6.3%) into unlikely, and 2 (1.8%) into very unlikely viral bands. Approximately 94% of patients had IMX-BVN-3 unlikely or very unlikely bacterial results. Among 7 (6.3%) patients with possible (n = 4) or very likely (n = 3) bacterial results, 6 (85.7%) had clinically adjudicated bacterial coinfection or superinfection. Overall, 19 of 111 subjects for whom adjudication was performed had a bacterial infection; 7 of these showed a very likely or likely bacterial result in IMX-BVN-3.
CONCLUSIONS
IMX-BVN-3 identified COVID-19 patients as virally infected and identified bacterial coinfections and superinfections. Future studies will determine whether a point-of-care version of the classifier may improve the management of COVID-19 patients, including appropriate antibiotic use.
PubMed: 36111173
DOI: 10.1093/ofid/ofac437 -
World Journal of Gastroenterology Aug 2019Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher... (Review)
Review
Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher risk for developing cirrhosis and hepatocellular carcinoma. Delta virus is a defective RNA virus that requires hepatitis B surface antigen for propagation in humans. Infection can occur in the form of a co-infection with hepatitis B, which can be self-limiting, superinfection in a patient with established hepatitis B infection, which often leads to chronicity in majority of cases. Current noninvasive tools to assess for advanced liver disease have limited utility in delta hepatitis. Guidelines recommend treatment with pegylated interferon, but this is limited to patients with compensated disease and is efficacious in about 30% of those treated. Due to limited treatment options, novel agents are being investigated and include entry, assembly and export inhibitors of viral particles in addition to stimulators of the host immune response. Future clinical trials should take into consideration the interaction of hepatitis B and hepatitis D as suppression of one virus can lead to the activation of the other. Also, surrogate markers of treatment efficacy have been proposed.
Topics: Antiviral Agents; Coinfection; Drug Therapy, Combination; Global Burden of Disease; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis D, Chronic; Hepatitis Delta Virus; Humans; Interferon-alpha; Lipopeptides; Organic Anion Transporters, Sodium-Dependent; Piperidines; Pyridines; Randomized Controlled Trials as Topic; Review Literature as Topic; Superinfection; Symporters; Therapies, Investigational; Treatment Outcome; Virus Assembly; Virus Internalization
PubMed: 31528088
DOI: 10.3748/wjg.v25.i32.4580 -
Journal of Virology Nov 2021Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the...
Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the pathogenesis of foot-and-mouth disease virus (FMDV) coinfections is largely unknown. In the current study, cattle were experimentally exposed to two FMDV strains of different serotypes (O and A). One cohort was simultaneously infected with both viruses, while additional cohorts were initially infected with FMDV A and subsequently superinfected with FMDV O after 21 or 35 days. Coinfections were confirmed during acute infection, with both viruses concurrently detected in blood, lesions, and secretions. Staggered exposures resulted in overlapping infections as convalescent animals with persistent subclinical FMDV infection were superinfected with a heterologous virus. Staggering virus exposure by 21 days conferred clinical protection in six of eight cattle, which were subclinically infected following the heterologous virus exposure. This effect was transient, as all animals superinfected at 35 days post-initial infection developed fulminant FMD. The majority of cattle maintained persistent infection with one of the two viruses while clearing the other. Analysis of viral genomes confirmed interserotypic recombination events within 10 days in the upper respiratory tract of five superinfected animals from which the dominant genomes contained the capsid coding regions of the O virus and nonstructural coding regions of the A virus. In contrast, there were no dominant recombinant genomes detected in samples from simultaneously coinfected cattle. These findings inculpate persistently infected carriers as potential FMDV mixing vessels in which novel strains may rapidly emerge through superinfection and recombination. Foot-and-mouth disease (FMD) is a viral infection of livestock of critical socioeconomic importance. Field studies from areas of endemic FMD suggest that animals can be simultaneously infected by more than one distinct variant of FMD virus (FMDV), potentially resulting in emergence of novel viral strains through recombination. However, there has been limited investigation of the mechanisms of FMDV coinfections under controlled experimental conditions. Our findings confirmed that cattle could be simultaneously infected by two distinct serotypes of FMDV, with different outcomes associated with the timing of exposure to the two different viruses. Additionally, dominant interserotypic recombinant FMDVs were discovered in multiple samples from the upper respiratory tracts of five superinfected animals, emphasizing the potential importance of persistently infected FMDV carriers as sources of novel FMDV strains.
Topics: Animals; Antibodies, Viral; Carrier State; Cattle; Cattle Diseases; Coinfection; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Livestock; Persistent Infection; Serogroup
PubMed: 34586864
DOI: 10.1128/JVI.01650-21 -
QJM : Monthly Journal of the... Nov 2021Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19).
AIM
To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients.
DESIGN
A systematic review and meta-analysis.
METHODS
Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses.
RESULTS
Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93).
CONCLUSION
The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.
Topics: Adult; Antibodies, Monoclonal, Humanized; Humans; Respiration, Artificial; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34010403
DOI: 10.1093/qjmed/hcab142 -
International Journal of Infectious... Jun 2022Following a study of predictors of superinfection in viral respiratory tract infections (VRTIs), this study analyzes the predictors of the outcome.
Superinfection is associated with short-term outcome and mortality in viral respiratory tract infections during the fall-winter seasons 2016-2018 in the Greater Paris area: the SUPERFLUOUS study: outcomes of viral infections.
BACKGROUND
Following a study of predictors of superinfection in viral respiratory tract infections (VRTIs), this study analyzes the predictors of the outcome.
METHODS
Multicenter retrospective study conducted among adults who tested positive for VRTIs with reverse-transcription polymerase chain reaction. We compared characteristics between influenza virus, Paramyxoviridae, and Pneumoviridae and identified predictors of favorable short-term outcome, admission to the intensive care unit (ICU), and mortality.
RESULTS
A total of 590 patients had VRTI, including 347 (59%) influenza infections. Mean (SD) patient age was 71.0 (18.3) years, with a sex ratio of 0.91. In multivariate analyses, predictors of favorable short-term outcome were age ≤75 years (adjusted odds ratio [aOR] 5.38 [95% confidence interval, 1.59-18.2]), absence of respiratory disease (4.94 [1.01-24.37]), and absence of superinfection (aOR 3.91 [1.37-11.13]). The predictors of ICU admission were age ≤75 years (aOR 3.28 [1.71-6.25]), chronic respiratory disease (aOR 2.49 [1.20-5.19]), and procalcitonin level >0.25 ng/mL (aOR 4.25 [1.55-11.67]). Predictors of mortality were use of inhaled corticosteroids (2.49 [1.10-5.63]), influenza infection (2.73 [1.27-5.85]), Charlson score ≥5 (5.35 [1.90-15.05]), superinfection (2.54 [1.05-6.18]), and eosinophil count <50/µL (4.39 [1.19-16.2]). Certainty of superinfection was significantly associated with mortality (2.23 [1.15-4.3]).
CONCLUSION
Our study revealed that superinfection was significantly related to the outcome, and that virus species affects mortality. These findings emphasize the need for improving the tools used in daily practice to confirm certainty of superinfection and for broader implementation of vaccination of individuals at risk of VRTIs.
Topics: Adult; Aged; Humans; Influenza, Human; Paris; Respiratory Tract Infections; Retrospective Studies; Seasons; Superinfection; Virus Diseases
PubMed: 35405349
DOI: 10.1016/j.ijid.2022.04.008 -
Journal of Fungi (Basel, Switzerland) May 2023This study systematically reviewed fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients. A PRISMA systematic search was conducted. On... (Review)
Review
This study systematically reviewed fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients. A PRISMA systematic search was conducted. On September 2022, Medline, PubMed, Google Scholar, PsychINFO, Wiley Online Library, NATURE, and CINAHL databases were searched for all relevant articles published in English. All articles that exclusively reported the presence of fungal-bacterial co-infections and super-infections among hospitalized COVID-19 patients were included. Seven databases produced 6937 articles as a result of the literature search. Twenty-four articles met the inclusion criteria and were included in the final analysis. The total number of samples across the studies was 10,834, with a total of 1243 (11.5%) patients admitted to the intensive care unit (ICU). Of these patients, 535 underwent mechanical ventilation (4.9%), 2386 (22.0%) were male, and 597 (5.5%) died. Furthermore, hospitalized COVID-19 patients have a somewhat high rate (23.5%) of fungal-bacterial co-infections and super-infections. Moreover, for SARS-CoV-2 patients who have a chest X-ray that suggests a bacterial infection, who require immediate ICU admission, or who have a seriously immunocompromised condition, empiric antibiotic therapy should be taken into consideration. Additionally, the prevalence of co-infections and super-infections among hospitalized COVID-19 patients may have an impact on diagnosis and treatment. It is crucial to check for fungal and bacterial co-infections and super-infections in COVID-19 patients.
PubMed: 37367534
DOI: 10.3390/jof9060598 -
PLoS Computational Biology Mar 2024Plasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa.... (Review)
Review
Plasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa. One of the significant characteristics of the P. vivax parasite is its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.e. relapse infections). Mathematical modelling approaches have been widely applied to understand P. vivax dynamics and predict the impact of intervention outcomes. Models that capture P. vivax dynamics differ from those that capture P. falciparum dynamics, as they must account for relapses caused by the activation of hypnozoites. In this article, we provide a scoping review of mathematical models that capture P. vivax transmission dynamics published between January 1988 and May 2023. The primary objective of this work is to provide a comprehensive summary of the mathematical models and techniques used to model P. vivax dynamics. In doing so, we aim to assist researchers working on mathematical epidemiology, disease transmission, and other aspects of P. vivax malaria by highlighting best practices in currently published models and highlighting where further model development is required. We categorise P. vivax models according to whether a deterministic or agent-based approach was used. We provide an overview of the different strategies used to incorporate the parasite's biology, use of multiple scales (within-host and population-level), superinfection, immunity, and treatment interventions. In most of the published literature, the rationale for different modelling approaches was driven by the research question at hand. Some models focus on the parasites' complicated biology, while others incorporate simplified assumptions to avoid model complexity. Overall, the existing literature on mathematical models for P. vivax encompasses various aspects of the parasite's dynamics. We recommend that future research should focus on refining how key aspects of P. vivax dynamics are modelled, including spatial heterogeneity in exposure risk and heterogeneity in susceptibility to infection, the accumulation of hypnozoite variation, the interaction between P. falciparum and P. vivax, acquisition of immunity, and recovery under superinfection.
Topics: Animals; Humans; Plasmodium vivax; Superinfection; Malaria, Vivax; Malaria; Models, Theoretical; Malaria, Falciparum; Parasites; Recurrence
PubMed: 38483975
DOI: 10.1371/journal.pcbi.1011931 -
Global Pediatric Health 2023Meningocele is a rare congenital malformation of the central nervous system resulting from a herniation of the meninges containing cerebrospinal fluid through a bony...
Meningocele is a rare congenital malformation of the central nervous system resulting from a herniation of the meninges containing cerebrospinal fluid through a bony defect in the skull. It is part of neural tube closure anomalies. The overall incidence of meningocele is 0.8 to 3 per 10 000 live births; it varies based on geographical location and race, with a predominance of occipital localization. Among diagnostic methods, computed tomography (CT) and magnetic resonance imaging (MRI) remain crucial examinations. Prenatal diagnosis of this malformation primarily relies on ultrasound and screening through maternal serum alpha-fetoprotein (AFP) levels. They typically manifest very early at birth with a highly suggestive radioclinical presentation. Surgical treatment usually allows for a definitive cure. Superinfection and rupture of the meningocele are exceptional, resulting from delayed diagnosis and management. In several developed countries, prevention through genetic counseling and the intake of folic acid during the periconceptional period, along with accurate prenatal diagnosis and the legalization of therapeutic abortion, has led to a decrease in the prevalence of meningoceles. In less developed countries, where there is a delay in diagnosis in exceptional cases, superinfection and rupture may occur. We present the case of an 8-month-old infant with a complicated occipital meningocele with superinfection and rupture.
PubMed: 37846398
DOI: 10.1177/2333794X231204498 -
Microbial Genomics Mar 2022Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages may impact COVID-19 disease progression and provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well phylogenetically defined, but two main factors have precluded major coinfection/codetection and recombination analysis thus far: (i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic, which limited the identification of lineage defining mutations necessary to distinguish coinfecting/recombining viral lineages; and the (ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we assembled a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. This approach enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations, representing 0.61 % of all samples investigated. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming its plausibility with the cocirculating lineages at the timeframe investigated. Our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, although it is certainly a lower bound estimate considering the difficulty to detect coinfections with very similar SARS-CoV-2 lineages and the low number of samples sequenced from the total number of infections.
Topics: Brazil; COVID-19; Coinfection; Genome, Viral; Humans; Mutation; Phylogeny; Polymorphism, Single Nucleotide; SARS-CoV-2; Superinfection
PubMed: 35297757
DOI: 10.1099/mgen.0.000751