Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Abstract

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

Respiratory Syncytial Virus: An Uncommon Cause of Febrile Seizures—Results from a Systematic Review and Meta-Analysis

“…The significance of the sampling issue is also stressed by the heterogenous occurrence of FS among sampled studies when assessed by their geographical settings. Despite some genetic risk factors for FS during respiratory infections being reported [ 20 , 21 , 22 , 38 , 39 , 44 ], including a substantially higher risk for FS in individual of Asiatic descent [ 20 , 22 , 35 ], we cannot rule out that our data more simply did reflect a different approach to hospitalization for respiratory infectious syndromes, with higher rates reflecting a more selective approach to hospitalizations.…”

“…In other words, FS in cases of RSV infections do occur, but healthcare providers could expect a substantially lower rate than in other respiratory infections, and particularly among SIV cases. Even though RSV infections have been linked to substantial CNS short- and long-term sequelae [ 38 , 39 , 40 ], the underlying mechanisms are reasonably quite distinctive from the causes of FS in respiratory disorders, including RSV [ 38 ]. While the sequelae of RSV infection have been tentatively associated with direct infection of cells within the CNS [ 38 , 41 ], FS in respiratory viral infection are supposedly the consequence of the “cytokine storm” elicited by the pathogen in the respiratory tract and reaching the CNS [ 20 , 21 , 22 , 42 ].…”

“…Even though RSV infections have been linked to substantial CNS short- and long-term sequelae [ 38 , 39 , 40 ], the underlying mechanisms are reasonably quite distinctive from the causes of FS in respiratory disorders, including RSV [ 38 ]. While the sequelae of RSV infection have been tentatively associated with direct infection of cells within the CNS [ 38 , 41 ], FS in respiratory viral infection are supposedly the consequence of the “cytokine storm” elicited by the pathogen in the respiratory tract and reaching the CNS [ 20 , 21 , 22 , 42 ]. According to some models, the passage of cytokines into the CNS would induce seizures either directly, through their effect on certain neuronal receptors (mostly, GABA receptors), or indirectly, as a consequence of the high temperatures induced by the hypothalamic stimulation, with increased recycling of synaptic vesicles, their enlargement, and the eventual enhancement of synaptic transmission [ 20 , 21 , 22 , 24 , 25 , 39 , 40 , 41 , 43 ].…”

“…While RSV-induced IL-6 and IL-8 production usually requires CNS cells infection, SIV appears quite effective in inducing high levels of these cytokines without the direct invasion of the nervous system [ 44 , 45 ]. In other words, only a reduced subset of RSV cases, i.e., those characterized by more extensive and/or a certain and direct involvement of CNS, would develop noticeable signs of encephalopathy, including FS, irrespective of the background characteristics of the febrile syndrome (e.g., the peak temperature, and the time requested to reach it) [ 23 , 38 , 44 ]. The higher occurrence of FS among studies including PICU cases may be explained accordingly, i.e., through the higher occurrence of complicated cases, with an invasive RSV infection compared to other clinical reports.…”

New Developments and Challenges in Antibody-Based Therapies for the Respiratory Syncytial Virus

“…16,17 Nevertheless, it is important to note that healthy infants born at term are also at risk for severe hRSV pneumonia (albeit to a lesser degree than preterm infants), and due to the ubiquity of the virus, make up most cases. 4,12,13,18 Additionally, substantial evidence has emerged that infection with this virus, including infections acquired during infancy, is associated with long-lasting chronic sequelae, including neuropsychiatric alterations, [19][20][21][22][23][24] asthma, airway dysfunction, and susceptibility to allergies. These latter three consequences are associated with the highly inflammatory immune response that hRSV elicits.…”