Epidemiology and Immune Pathogenesis of Viral Sepsis

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• In addition, the systemic inflammatory response syndrome (SIRS) criteria, which were the essential elements of Sepsis-1 and Sepsis-2, are no longer used to define sepsis, but they still play a role in the recognition of infection and warrant early intervention for possible sepsis

• Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases.

• The current, widely-used consensus definition of paediatric sepsis, proposed in 2005, was still built on the SIRS criteria

• In some cases, viral sepsis is regarded as virus-induced direct tissue or cell damage (e.g., influenza virus-induced pulmonary epithelial damage) instead of systemic dysregulation caused by virus.

• Therefore, in this review article, viral sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to viral infection in both adult and paediatric populations.

• Viral sepsis should always be considered in septic patients lacking evidence of bacterial, parasitic or fungal infection, and laboratory tests for viruses should be arranged accordingly.

• In general, the incidence and severity of sepsis are climbing over time, whereas sepsis-associated mortality is declining (16–19).

• Organisms that contribute to sepsis can be identified in 59–69% of septic patients (i.e., documented sepsis), with bacteria usually accounting for more than 70% of the documented sepsis cases

• Viruses only contribute ~1% of the documented sepsis cases in some studies (22, 23).

• The most common viruses identified were dengue viruses (27%), followed by rhinovirus (23%), influenza viruses (14%), and respiratory syncytial virus (12%).

• However, the identified viruses could be the single causative agent of sepsis (e.g., dengue), a contributor to secondary bacterial sepsis (e.g., influenza and staphylococcal sepsis) (25), coinfection of unknown significance (e.g., rhinovirus), prolonged or persistent shedding of a previous infection (e.g., adenovirus) (26), an “innocent” latent infection (e.g., Epstein-Barr virus) or a false positive result.

• This also needs to be taken in the clinical context.

• This uncertainty is another major obstacle to studying the epidemiology of viral sepsis, particularly in cases where bacterial infection is also documented or the identified virus does not usually cause fulminant disease.

• What role the identified virus plays in a septic patient is still an area of debate.

• Similarly, another prospective study demonstrated that a third of adult patients requiring intensive care for severe pneumonia had viral infections, detected by a predefined array of diagnostic tests (including PCR tests for multiple viruses) (27)

• Moreover, another prospective study found that patients with culture-negative sepsis had significantly lower levels of procalcitonin than those with documented sepsis

• there is an urgent need to understand the epidemiology of viral sepsis.

• Aetiology of viral sepsis

• Herpes simplex virus (HSV) and enteroviruses are the most common viral causes of neonatal sepsis

• In addition, influenza viruses are not only a major cause of severe infections and deaths among children younger than 5 years of age, older adults, pregnant women and immunosuppressed individuals (34), but can also lead to substantial morbidity and mortality in older children and adults in other age groups