Central Effects of Ivermectin in Alleviation of Covid-19-induced Dysautonomia

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory abnormality, and deregulation of the renin-angiotensin system (RAS) may increase sympathetic discharge with dysautonomia development. Direct SARS-CoV-2 cytopathic effects and associated inflammatory reaction may lead to neuroinflammation, affecting different parts of the central nervous system (CNS), including the autonomic center in the hypothalamus, causing dysautonomia. High circulating AngII, hypoxia, oxidative stress, high pro-inflammatory cytokines, and emotional stress can also provoke autonomic deregulation and high sympathetic outflow with the development of the sympathetic storm. During SARS-CoV-2 infection with neuro-invasion, GABA-ergic neurons and nicotinic acetylcholine receptor (nAChR) are inhibited in the hypothalamic pre-sympathetic neurons leading to sympathetic storm and dysautonomia. Different therapeutic modalities are applied to treat SARS-CoV-2 infection, like antiviral and anti-inflammatory drugs. Ivermectin (IVM) is a robust repurposed drug widely used to prevent and manage mild-moderate Covid-19. IVM activates both GABA-ergic neurons and nAChRs to mitigate SARS-CoV-2 infection- induced dysautonomia. Therefore, in this brief report, we try to identify the potential role of IVM in managing Covid-19-induced dysautonomia.