Reset of Virus-Hijacked NRP1
Neuropilin (NRP)-1 is expressed in olfactory epithelium, astrocytes, and neuronal cells (which lack ACE2 expression) and serve as major CSR for SARS‐CoV‐2 infection of the central nervous system (CNS). Viral hijack of NRP1 facilitates CNS invasion of SARS-CoV-2 through the blood brain barrier (BBB), and consequential neuro-cognitive symptoms such as anosmia, ageusia, headaches, confusion, delirium, and strokes in early COVID-19. The ensuing pathophysiology involves viral-induced neuronal damage, neuroinflammation, rupture of the BBB, microvasculitis and hypoxia. Neuroinflammation with hypometabolic lesions cause chronic cognitive impairment in COVID patients. Neurological manifestations in viral-induced HMR/D include damage to CNS and PNS, encephalitis, myelitis, myositis, Guillain Barré syndromes, and cognitive impairments. These neuro-complications are prevalent among one third of COVID-19 cases, and this clinical condition may persist as chronic symptoms in PASC patients as frequent complaints of brain fog (81%) and fatigue (58%). Nutritional reset of neuro-cognitive dysfunction from viral hijack of NRP1 indeed is of high priority in clinical management of viral-induced HMR/D.
Melatonin: Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of tryptophan, synthesized/secreted by
the pineal gland and reaches peak levels in plasma during the night hours. This chrono-biotic hormone serves as a photo-periodic switch, influencing the activity of suprachiasmatic nucleus and facilitates human sleep-wake. Melatonin plays a multi-functional role including the regulation of circadian rhythms, immune modulation, oxidative processes, apoptosis, and mitochondrial homeostasis. Melatonin deficiency may lead to cardiovascular disease with manifestations of hypertension and myocardial ischemia/reperfusion injury, which are prevalent in COVID-19; as well as neuro-cognitive complications such as brain fog, sleep disorders and ME/CFS, which are persistent among PASC. Melatonin with its antioxidant, anti-inflammatory, immune-modulatory, and anti-apoptotic effects, is considered a potential therapeutic reset for viral-induced HMR/D. Based on several human RCTs, melatonin is considered an effective intervention to resolve delirium, ameliorate respiratory stress (i.e., ARDS), and restore circadian balance in viral-induced HMR/D.