Neuroendocrine involvement and retinoid signaling disorder in COVID-19: A different perspective on neuroendocrine involvement, menstrual irregularities and reproductive dysfunctions in COVID-19

Despite the intense work of researchers since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet understood. Accordingly, the mechanism behind menstrual irregularities, abnormal uterine bleeding, abortions and reproductive problems in women has not been clearly clarified. Current information and a broad analysis of the literature suggest that retinol depletion and retinoid signaling defect may underlie the gynecological and reproductive problems seen in COVID-19. Retinol depletion and retinoid signaling disorder seen in COVID-19 can clearly explain the involvement in endocrine organs such as thyroid, pancreas and adrenal glands, apart from the disorders seen in the female genital system. It is known that SARS-CoV-2 causes chemosensory receptor disorders and exerts its pathogenic effects through these mechanisms. The relatively low expression of ACE2 receptors in the brain and endocrine organs, which are responsible for the invasion of SARS-CoV2 into host cells in COVID-19, is insufficient to explain the severe involvement of these organs. Systemic involvement and multi-organ damage in COVID-19 also suggest that the pathogenetic disorder in COVID-19 develops through multiple receptors and signaling pathways. As a result of impaired retinoid activity in neuroendocrine and genital organs in COVID-19, GPCR and STRA6 receptor synthesis and function are also impaired. Likewise, the synthesis of GPCR and STRA6 receptors occurs depending on retinoid activity. Retinoid activity and its associated STRA6 and GPCR receptors are densely located in the limbic system, which is the center of emotional activity in the brain, and in the thalamus, hypothalamus, pituitary gland and reproductive organs, which is the center of neuroendocrine regulation. This suggests that the excessive uterine bleeding, endocrine system and reproductive disorders in COVID-19 are caused by the deterioration of retinoid activity in this region. Likewise, the high expression of GPCRS and GnRH receptors in the brain and endocrine organs is in parallel with the neuroendocrine and genital organ involvement of COVID-19. The retinoid signaling defect, associated signaling pathways and receptors illuminate the complex mechanism of neuroendocrine involvement and peripheral organ involvement in COVID-19.