Loneliness: An Immunometabolic Syndrome.

Loneliness has been defined as an agonizing encounter, experienced when the need for human intimacy is not met adequately, or when a person's social network does not match their preference, either in number or attributes. This definition helps us realize that the cause of loneliness is not merely being alone, but rather not being in the company we desire. With loneliness being introduced as a measurable, distinct psychological experience, it has been found to be associated with poor health behaviors, heightened stress response, and inadequate physiological repairing activity. With these three major pathways of pathogenesis, loneliness can do much harm; as it impacts both immune and metabolic regulation, altering the levels of inflammatory cytokines, growth factors, acute-phase reactants, chemokines, immunoglobulins, antibody response against viruses and vaccines, and immune cell activity; and affecting stress circuitry, glycemic control, lipid metabolism, body composition, metabolic syndrome, cardiovascular function, cognitive function and mental health, respectively. Taken together, there are too many immunologic and metabolic manifestations associated with the construct of loneliness, and with previous literature showcasing loneliness as a distinct psychological experience and a health determinant, we propose that loneliness, in and of itself, is not just a psychosocial phenomenon. It is also an all-encompassing complex of systemic alterations that occur with it, expanding it into a syndrome of events, linked through a shared network of immunometabolic pathology. This review aims to portray a detailed picture of loneliness as an "immunometabolic syndrome", with its multifaceted pathology.

Altered immunoemotional regulatory system in COVID-19: From the origins to opportunities.

The emergence of the novel coronavirus (SARS-CoV-2) and the worldwide spread of the coronavirus disease (COVID-19) have led to social regulations that caused substantial changes in manners of daily life. The subsequent loneliness and concerns of the pandemic during social distancing, quarantine, and lockdown are psychosocial stressors that negatively affect the immune system. These effects occur through mechanisms controlled by the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenocortical (HPA) axis that alter immune regulation, namely the conserved transcriptional response to adversity (CTRA), which promotes inflammation and diminishes antiviral responses, leading to inadequate protection against viral disease. Unhealthy eating habits, physical inactivity, sleep disturbances, and mental health consequences of COVID-19 add on to the pathological effects of loneliness, making immunity against this ferocious virus an even tougher fight. Therefore, social isolation, with its unintended consequences, has inherently paradoxical effects on immunity in relation to viral disease. Though this paradox can present a challenge, its acknowledgment can serve as an opportunity to address the associated issues and find ways to mitigate the adverse effects. In this review, we aim to explore, in detail, the pathological effects of the new social norms on immunity and present suggested methods to improve our physical, psychological, and healthcare abilities to fight viral infection in the context of the COVID-19 pandemic.

COVID-19 and Neurological Impairment: Hypothalamic Circuits and Beyond.

In December 2019, a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of Hubei, China. The virus infection, coronavirus disease 2019 (COVID-19), represents a global concern, as almost all countries around the world are affected. Clinical reports have confirmed several neurological manifestations in COVID-19 patients such as headaches, vomiting, and nausea, indicating the involvement of the central nervous system (CNS) and peripheral nervous system (PNS). Neuroinvasion of coronaviruses is not a new phenomenon, as it has been demonstrated by previous autopsies of severe acute respiratory syndrome coronavirus (SARS-CoV) patients who experienced similar neurologic symptoms. The hypothalamus is a complex structure that is composed of many nuclei and diverse neuronal cell groups. It is characterized by intricate intrahypothalamic circuits that orchestrate a finely tuned communication within the CNS and with the PNS. Hypothalamic circuits are critical for maintaining homeostatic challenges including immune responses to viral infections. The present article reviews the possible routes and mechanisms of neuroinvasion of SARS-CoV-2, with a specific focus on the role of the hypothalamic circuits in mediating the neurological symptoms noted during COVID-19 infection.