Influenza progression stages

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Influenza Progression Stages: SEIR Model and Disease Dynamics

The progression of influenza infection is commonly described using the SEIR model, which includes four main stages: Susceptible, Exposed (Latent), Infectious, and Removed (Recovered or Dead) . After exposure, individuals enter a latent period averaging about 1.6 days, during which they are infected but not yet infectious. This is followed by the infectious period, which lasts about 1.0 day on average, with only a small percentage of cases remaining infectious for more than 2.9 days . Rapid isolation or treatment shortly after symptom onset is crucial to prevent further transmission, as most secondary cases occur early in the infectious period .

Molecular and Cellular Changes During Influenza Progression

Early and Asymptomatic Stages

At the initial, often asymptomatic stage, the host mounts a local inflammatory response in the lungs, characterized by increased pro-inflammatory cytokines and an influx of inflammatory monocytes, even before symptoms appear . In asymptomatic infections, the host tightly regulates antiviral and inflammatory responses, showing elevated expression of genes involved in antioxidant and cell-mediated responses, which may help prevent progression to symptomatic disease .

Symptomatic and Severe Stages

As the infection progresses to symptomatic stages, there is a marked upregulation of antiviral and inflammatory pathways, including those mediated by pattern recognition receptors . In severe cases, there is a significant increase in neutrophil-related pathways, such as neutrophil differentiation, migration, degranulation, and the formation of neutrophil extracellular traps (NETs) . At the same time, immune response pathways, including those involving CD4+ and CD8+ T cells and natural killer (NK) cells, are downregulated, as are apoptosis pathways . This dysregulation is associated with a higher risk of severe disease and complications.

Severe influenza is also marked by abnormal changes in cell cycle and apoptosis pathways in circulating leukocytes. There is increased DNA replication in the G1/S phase but delayed progression in the G2/M phase, and a loss of integration between cell cycle control and apoptosis, which distinguishes severe from mild infections .

Clinical Outcomes and Risk Factors for Progression

Progression from mild to severe influenza is influenced by several factors, including age, immunosuppression, and delayed hospital admission . Hospitalized patients, especially those admitted to intensive care units, have a higher risk of poor outcomes, including prolonged hospitalization and death . The prognosis is generally worse during pandemic periods compared to seasonal influenza .

Staged Progression and Retrogression Models

Mathematical models of influenza progression, such as the staged progression and retrogression model, allow for variable chain lengths and the possibility of moving backward between stages, reflecting the complex and sometimes non-linear course of the disease . These models help capture the variability in disease progression and are useful for understanding and predicting influenza dynamics in populations .

Cellular Entry and Early Infection Events

At the cellular level, influenza virus entry involves a three-stage transport process within host cells: actin-dependent movement at the cell periphery, rapid dynein-directed translocation to the perinuclear region, and intermittent microtubule-based motility. Initial acidification and endosome maturation, crucial for viral fusion and infection, occur mainly in the perinuclear region .

Conclusion

Influenza progression involves distinct stages, from asymptomatic infection and early immune responses to symptomatic and potentially severe disease marked by immune dysregulation and cellular changes. The duration and severity of each stage are influenced by host factors and the timing of intervention. Understanding these stages and the underlying molecular and cellular mechanisms is essential for effective prevention, timely treatment, and improved outcomes in influenza infection Zerbib2020Cori2012Lynfield2014+5 MORE.

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Most relevant research papers on this topic

Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection

Severe influenza is associated with increased neutrophil activity and decreased immune response pathways, highlighting distinct pathogenic mechanisms in the progression from moderate to severe influenza infection.

Observational StudyRigorous Journal

2020·

22citations

·Y. Zerbib et al.

BMC Medical Genomics·

DOI

Estimating influenza latency and infectious period durations using viral excretion data.

Influenza infection latency and infectious period durations are 1.6 and 1.0 days on average, with only 5% of cases infectious for more than 2.9 days, and isolation or treatment must be implemented shortly after symptoms onset to avoid 50% of secondary cases.

Highly Cited

2012·

78citations

·A. Cori et al.

Epidemics·

DOI

Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies

Patients with influenza A(H1N1)pdm09, particularly those requiring hospital admission, are at high risk for disease progression, especially if older, immunodeficient, or admitted late in infection.

Rigorous Journal

2014·

38citations

·R. Lynfield et al.

PLoS ONE·

DOI

Human Influenza Virus Infections

Current antiviral strategies are insufficient for severe influenza infections, highlighting the need for novel therapies targeting the pulmonary host response to improve viral clearance, reduce bacterial coinfection, and prevent acute lung injury.

Highly Cited

2016·

217citations

·C. Peteranderl et al.

Seminars in Respiratory and Critical Care Medicine·

DOI

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

Symptomatic influenza A infection involves simultaneous antiviral and inflammatory responses, while asymptomatic individuals tightly regulate these responses and exhibit elevated antioxidant and cell-mediated responses.

Non-RCTHighly Cited

2011·

225citations

·Yongsheng Huang et al.

PLoS Genetics·

DOI

Aberrant Cell Cycle and Apoptotic Changes Characterise Severe Influenza A Infection – A Meta-Analysis of Genomic Signatures in Circulating Leukocytes

Severe influenza A infection is characterized by abnormal transcriptional reprogramming of cell cycle and apoptosis pathways, leading to the loss of integration between cell cycle perturbations and apoptosis.

Meta-Analysis

2011·

66citations

·G. Parnell et al.

PLoS ONE·

DOI

Visualizing infection of individual influenza viruses

Influenza viruses enter cells through a three-stage active transport process, with initial acidification occurring in the perinuclear region, suggesting a previously undescribed scenario in the endocytic pathway.

In Vitro StudyHighly Cited

2003·

730citations

·M. Lakadamyali et al.

Proceedings of the National Academy of Sciences of the United States of America·

DOI

Innate immune responses at the asymptomatic stage of influenza A viral infections of Streptococcus pneumoniae colonized and non-colonized mice

Influenza A virus challenge in healthy mice does not automatically result in severe co-infection, but a general local inflammatory response is observed at the asymptomatic stage, regardless of infection type.

Non-RCTAnimal StudyRigorous Journal

2021·

15citations

·Fabian Cuypers et al.

Scientific Reports·

DOI

Progression and Trends in Virus from Influenza A to COVID-19: An Overview of Recent Studies

COVID-19 has rapidly spread worldwide, with key similarities and differences to influenza A, and recent progress in diagnosis and treatment approaches.

Literature Review

2021·

16citations

·Hakimeh Baghaei Daemi et al.

Viruses·

DOI

Early peripheral blood lymphocyte subsets and cytokines in predicting the severity of influenza B virus pneumonia in children

Early lymphocyte count and cytokines can predict the severity of influenza B virus pneumonia in children, with reduced CD8+ T cell and NK cell count being independent risk factors.

Observational Study

2023·

12citations

·Lu Ma et al.

Frontiers in Cellular and Infection Microbiology·

DOI

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