A Novel Link between Early Life Allergen Exposure and Neuroimmune Development in Children.

Purpose: As COVID-19 unprecedented situation significantly increased the time families spend indoors, the awareness of unhealthy living conditions negatively impacting immune system and early neurodevelopment of children is of crucial importance.

Methods: We retrospectively reviewed unrelated cases of the children with confirmed multiple indoor allergen sensitization due to prolonged exposure to unhealthy indoor environment with infestation and water damage, who, in addition to multiple health problems related to allergy and asthma, also developed neuroimmune complications and growth delay.

Results: Documented early in life atypical neurologic and behavioral changes were common in all cases. Clinical analysis did not establish other causative reason aside from prenatal and early life exposure to unhealthy living conditions. Alternaria Alternara and Penicillium/Aspergillus molds were found in all homes and sensitization was confirmed in all cases. Significant similarities in the symptoms recorded in all three families led us to a hypothesis that, likely, a significant level of the immune response to external immunogenic pathological stimulus such as mold spore protein, mycotoxin protein, dust mite protein, decay-related volatile particles (VOC) skewed a balance of the neuroimmune interactions, and further affected neuronal network establishment. As all children exhibited significant spectrum of the systemic inflammatory conditions early in life, coupled with inability to follow normal neurodevelopment, we hypothesize that an overwhelming activation of the aggressive immune mechanisms by the epigenetic factors led to glia activation, cytokine storm and break of tolerance.

Conclusions: We hypothesize that developing immune system exhibited aggressive responses due to environmental danger signals, subsequently TH-1 or TH-2 switch enables multiple clinical syndromes development with atypical presentation due to the described novel mechanism. An increased due to the COVID-19 lock-down may increase an amount of exposure of vulnerable people to indoor biological particles and volatile organic compounds present in unhealthy buildings. It is of crucial importance to identify and remediate indoor exposure factors that can decrease immune protection, especially against infectious pathogens such as novel coronavirus.