Viral Sepsis in Children

Gupta, Neha; Richter, Robert; Robert, Stephen; Kong, Michele

The constitutional symptoms and clinical features of viral sepsis are frequently indistinguishable from bacterial or fungal sepsis. Presenting symptoms and signs include fever, chills, rash, respiratory distress, nausea, vomiting, diarrhea, dysuria, confusion, and altered mental status. None of these symptoms is pathognomonic of sepsis, let alone viral induced sepsis. Moreover, classic features of systemic inflammation might not be seen in every individual, especially in immunocompromised children. Fever is one of the most common symptoms seen in septic children, attributable to the pyrogenic activity of IL-1, IL-6, IFNs, and TNF-α. It has been observed that these substances increase prostaglandin E2 synthesis in the hypothalamus (73, 74) , resulting in the elevation in the host central nervous system core temperature set-point regulated by the pre-optic and dorsomedial hypothalamic nuclei (75) . Hypothermia, on the other hand, is a less frequent but more specific indicator of sepsis that may be predictive of illness severity and death, especially in younger children and chronically debilitated patients (74) . Injury to the vascular endothelium may result in broad array of failing FIGURE 3 | Viral-induced host cytotoxicity through the extrinsic and intrinsic apoptotic pathways. Tumor necrosis factor-alpha (TNF-α) is released after viral recognition by the innate immune system, and TNF-related apoptosis-inducing ligand (TRAIL) is released from viral-reprogrammed macrophages, both of which bind their respective host cell surface death receptors to activate the extrinsic apoptotic pathway. Natural killer (NK) and cluster of differentiation 8 (CD8+) T cells inject perforin into the membranes of infected host cells, through which they secrete granzymes that elicit the intrinsic apoptotic pathway. The intrinsic pathway may be activated after viral protein recognition by the host cell or suicide gene insertion by cytotoxic viruses.