Social connection and gene regulation during the COVID-19 pandemic: Divergent patterns for online and in-person interaction.

BACKGROUND: Social connection has been linked to reduced disease risk and enhanced antiviral immunity, but it is unclear whether online social connections have similar effects to those previously documented for in-person/offline social relationships, or whether online connections can substitute for in-person social relations when the latter are restricted. We examined this question in the context of the COVID-19 pandemic, focusing specifically on an immune system gene regulation profile known as the conserved transcriptional response to adversity (CTRA), which is characterized by up-regulation of proinflammatory genes and down-regulation of genes linked to innate antiviral responses and antibody production. METHODS: We analyzed CTRA RNA profiles in blood samples from 142 healthy young adults (69% female, 87% white) during the "social distancing" period of the COVID-19 pandemic. Mixed effect linear models quantified the relation of CTRA gene expression to measures of in-person social connection (number of friends, social eudaimonia, loneliness) and online psychosocial connection (online loneliness, perceived social value in online leisure and educational contexts, and internet use) while controlling for demographic and health factors. RESULTS: Multiple indicators of in-person and generalized social connection were associated with lower CTRA gene expression, whereas no measure of online social connection showed any significant association with CTRA gene expression. CONCLUSION: Experiences of in-person social connection are associated with reduced CTRA gene expression during a period of restricted social interaction. In contrast, online social relationships show no such association. Digitally mediated social relations do not appear to substantially offset the absence of in-person/offline social connection in the context of immune cell gene regulation.

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.

Isolation, social stress, low socioeconomic status and its relationship to immune response in Covid-19 pandemic context.

The coronavirus disease 2019 (COVID-19) outbreak was first reported December 2019, in Wuhan, China, and has since spread worldwide. Social distancing or isolation measures were taken to mitigate the pandemic. Furthermore, stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality, what can be biologically observed. This condition tends to remain during the Covid-19 pandemic. Social disruption stress (SDR) raises important questions regarding the functioning of the immune system, and the release of several stress hormones. A molecular pattern, conserved transcriptional response to adversity (CTRA), is thought to have evolved to defend against physical injury during periods of heightened risk. Chronic CTRA activation could leave an organism vulnerable to viral infections, leading to increased pro-inflammatory gene expression and a suppression of anti-viral gene expression. The activation of such transcriptional status is related to conditions of social stress through either hostile human contact, or increased predatory vulnerability due to separation from the social group and also low socioeconomic status. This review aims to point out questions for government officials, researchers and health professionals to better target their actions during a pandemic and encourage studies for a better understanding of these characteristics.