Brain motor and fear circuits regulate leukocytes during acute stress.

The nervous and immune systems are intricately linked1. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood2. Here we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid neutrophil mobilization from the bone marrow to peripheral tissues through skeletal-muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signalling. These stress-induced, counter-directional, population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury. On the other hand, corticotropin-releasing hormone neuron-mediated leukocyte shifts protect against the acquisition of autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, therefore calibrating the ability of the immune system to respond to physical threats.

Ayurveda and COVID-19: Where psychoneuroimmunology and the meaning response meet.

The COVID-19 pandemic has led to high levels of psychological distress in the general public, including symptoms of anxiety and depression. Such distress is associated with alterations in immune function, including an elevated risk of viral respiratory tract infections. In this light, the possible effects of Ayurveda, a traditional system of medicine promoted by the Indian government as an "immune booster", are examined from the point of view of psychoneuroimmune mechanisms as well as the "meaning response" described by Moerman. It was found that many of the measures advocated in their guidelines could positively influence immunity either by direct effects on symptoms of depression or anxiety, or through their symbolic significance. Therefore, it is possible that such traditional practices could be beneficial both in terms of psychological quality of life, and in terms of moderating the risk of infection.

The dynamic changes of cellular immunity among frontline medical workers who supported Wuhan for fighting against the COVID-19.

The outbreak of novel coronavirus disease 2019 (COVID-19) poses a great stress to frontline medical workers. Our previous study indicated that immune cells in the peripheral blood of frontline medical workers changed significantly. However, the dynamic changes of immune cells of frontline medical workers remain unclear. Here, we reported the dynamic changes of lymphocyte subsets in the peripheral blood of 51 frontline medical worker. The frontline medical workers struggling with COVID-19 from February 8 to March 31, 2020. Demographic and clinical data, including routine blood test data were extracted from the electronic health examination record and retrospectively analyzed. The lymphocyte (LYM) count and LYM ratio increased while the monocyte (MONO) ratio, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and neutrophil (NEUT) ratio in the peripheral blood of frontline medical workers decreased 10 days after struggling with COVID-19. Interestingly, the differences of LYM count, LYM ratio, MONO ratio, NLR, NEUT ratio were more significantly in nurse than doctor. The differences of LYM ratio, NLR and NEUT ratio were more significantly in female than male. However, the changes of LYM count, LYM ratio, MONO ratio, NLR, MLR, NEUT ratio returned to the baseline 10 months after struggling with COVID-19. Together, these data indicated that immune cells in the peripheral blood changed significantly 10 days after struggling with COVID-19, but returned to normal after 10 months. Those maybe caused by psychological stress and we recommend to pay more attention to mental health and immune response of frontline medical workers.

The Exposome and Immune Health in Times of the COVID-19 Pandemic.

Growing evidence supports the importance of lifestyle and environmental exposures-collectively referred to as the 'exposome'-for ensuring immune health. In this narrative review, we summarize and discuss the effects of the different exposome components (physical activity, body weight management, diet, sun exposure, stress, sleep and circadian rhythms, pollution, smoking, and gut microbiome) on immune function and inflammation, particularly in the context of the current coronavirus disease 2019 (COVID-19) pandemic. We highlight the potential role of 'exposome improvements' in the prevention-or amelioration, once established-of this disease as well as their effect on the response to vaccination. In light of the existing evidence, the promotion of a healthy exposome should be a cornerstone in the prevention and management of the COVID-19 pandemic and other eventual pandemics.

Neuroimmune multi-hit perspective of coronaviral infection.

It is well accepted that environmental stressors experienced over a one's life, from microbial infections to chemical toxicants to even psychological stressors, ultimately shape central nervous system (CNS) functioning but can also contribute to its eventual breakdown. The severity, timing and type of such environmental "hits", woven together with genetic factors, likely determine what CNS outcomes become apparent. This focused review assesses the current COVID-19 pandemic through the lens of a multi-hit framework and disuses how the SARS-COV-2 virus (causative agent) might impact the brain and potentially interact with other environmental insults. What the long-term consequences of SAR2 COV-2 upon neuronal processes is yet unclear, but emerging evidence is suggesting the possibility of microglial or other inflammatory factors as potentially contributing to neurodegenerative illnesses. Finally, it is critical to consider the impact of the virus in the context of the substantial psychosocial stress that has been associated with the global pandemic. Indeed, the loneliness, fear to the future and loss of social support alone has exerted a massive impact upon individuals, especially the vulnerable very young and the elderly. The substantial upswing in depression, anxiety and eating disorders is evidence of this and in the years to come, this might be matched by a similar spike in dementia, as well as motor and cognitive neurodegenerative diseases.

The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.

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.

Nexus between COVID-19 and periodontal disease.

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.

Immune response of frontline medical workers providing medical support for Wuhan COVID-19 patients, China.

The outbreak of novel coronavirus disease 2019 (COVID-19) posed a great challenge and stress to frontline medical workers in China. Stress is closely related to immunity. However, the immune response of frontline medical workers providing medical support for COVID-19 patients is unclear. Here, we reported the immune response of 76 frontline medical workers and 152 controls from the Second Affiliated Hospital of Xi'an Jiaotong University. The frontline medical workers were involved in the care for Wuhan COVID-19 patients from February 8 to March 31, 2020 in Tongji Hospital of Huazhong University of Science and Technology. The controls were medical workers of our hospital who had not been in contact with COVID-19 patients during the same period. Demographic and clinical data, including routine blood test data were extracted from the electronic health examination record and retrospectively analyzed. The post-stress frontline medical workers had higher lymphocyte (LYM) count compared with controls or pre-stress. However, the post-stress frontline medical workers had lower monocyte (MONO) count, neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and neutrophil (NEUT) ratio than controls or pre-stress. Interestingly, we found the differences were more significantly in female subgroup and nurse subgroup. Together, these data indicated that changes of immune response were found in frontline medical workers providing medical support for Wuhan COVID-19 patients, especially in females and nurses. Those maybe caused by psychological stress and we recommend to pay more attention to mental health of frontline medical workers, and provide appropriate psychological interventions for them.

Effects of anxiety sensitivity, disgust, and intolerance of uncertainty on the COVID stress syndrome: a longitudinal assessment of transdiagnostic constructs and the behavioural immune system.

Excessive fear and worry in response to the COVID-19 pandemic (e.g., COVID stress syndrome) is prevalent and associated with various adverse outcomes. Research from the current and past pandemics supports the association between transdiagnostic constructs-anxiety sensitivity (AS), disgust, and intolerance of uncertainty (IU)-and pandemic-related distress. Recent research suggests a moderating effect of disgust on the relationship of AS-physical concerns and COVID-19-related distress, suggesting that transdiagnostic constructs underlie individual differences in activation of the behavioral immune system (BIS). No previous study has examined the independent and conjoint effects of pre-COVID-19 AS-physical concerns, disgust propensity (DP), disgust sensitivity (DS), and IU in this context; thus, we did so using longitudinal survey data (N = 3,062 Canadian and American adults) with simple and moderated moderations controlling for gender, mental health diagnosis, and COVID-19 diagnosis. Greater AS-physical concerns, DP, and DS predicted more severe COVID stress syndrome assessed one month later. Either DP or DS further amplified the effect of AS-physical concerns on COVID stress syndrome, except danger and contamination fears. IU did not interact with AS-physical concerns and DS or DP. Theoretical and clinical implications pertaining to delivery of cognitive behavioural therapy for pandemic-related distress are discussed.

[Can Stress Interact with SARS-CoV-2? A Narrative Review with a Focus on Stress-Reducing Interventions that may Improve Defence against COVID-19]. / Stress und Covid-19: Ein Narrativer Review über neuroendokrin-immune Mechanismen, die eine Abwehr von SARS-CoV-2 verbessern könnten.

OBJECTIVE: The COVID-19 pandemic is on the rise and causes many concerns and fears in the population as well as among medical care givers. This raises the question as to how psychosocial stress associated with the pandemic can be managed, and also if certain forms of stress can contribute to an increase in infections and critical illnesses. METHODS: Against the background of the current state of research on stress and the immune response, we provide a narrative review of studies addressing the question as to how stress can influence the immune defence against viral diseases. RESULTS: Excessive stress can compromise the barrier function of the airways and alter neuroendocrine control of immune function, which can create a virus-permissive immune response. DISCUSSION: Because certain forms of stress can play a role in the successful immune defence against viral respiratory disease, it is important to identify people with high psychosocial stress and to help them manage their stress. Conclusion Psychosocial measures that contribute to improved stress management may have a positive effect on the immune response against viral respiratory infections.

Use of Yoghurt Enhanced with Volatile Plant Oils Encapsulated in Sodium Alginate to Increase the Human Body's Immunity in the Present Fight Against Stress.

(1) Background: The COVID-19 pandemic and the imposition of strict but necessary measures to prevent the spread of the new coronavirus have been, and still are, major stress factors for adults, children, and adolescents. Stress harms human health as it creates free radicals in the human body. According to various recent studies, volatile oils from various aromatic plants have a high content of antioxidants and antimicrobial compounds. An external supply of antioxidants is required to destroy these free radicals. The main purpose of this paper is to create a yoghurt with high antioxidant capacity, using only raw materials from Romania; (2) Methods: The bioactive components used to enrich the cow milk yoghurt were extracted as volatile oils out of four aromatic plants: basil, mint, lavender and fennel. Initially, the compounds were extracted to determine the antioxidant capacity, and subsequently, the antioxidant activity of the yoghurt was determined. The 2,2-diphenyl-1-picrylhy-drazyl (DPPH) method was used to determine the antioxidant activity; (3) Results: The results show that cow milk yoghurt enhanced with volatile oils of basil, lavender, mint and fennel, encapsulated in sodium alginate has an antioxidant and antimicrobial effect as a staple food with multiple effects in increasing the body's immunity. The antioxidant activity proved to be considerably higher than the control sample. The highest antioxidant activity was obtained on the first day of the analysis, decreasing onwards to measurements taken on days 10 and 20. The cow milk yoghurt enriched with volatile basil oil obtained the best results; (4) Conclusions: The paper shows that yoghurts with a high antioxidant capacity were obtained, using only raw materials from Romania. A healthy diet, compliance with safety conditions and finding appropriate and safe methods to increase the body's immunity is a good alternative to a major transition through harder times, such as pandemics. The creation of food products that include natural antioxidant compounds combines both the current great possibility of developing food production in Romania and the prevention and reduction of the effects caused by pandemic stress in the human body.

Exercise and well-being during COVID 19 - time to boost your immunity.

INTRODUCTION: The COVID-19 pandemic is causing devastating global morbidity and mortality. Worldwide measures are taken to prevent human to human transmission and improve general health. Public lifestyle and health are affected by social distancing and isolation. A strong host immune response to the novel coronavirus is a key factor, for protection against infection and avoiding reaching severe stages of the disease. AREAS COVERED: Pathophysiology and the human immune response of similar coronaviruses have been previously described. The novel coronavirus has distinct clinical stages related to the immune response. Exercise improves host innate immunity and affords protection to viral infections. Exercise also mitigates the negative effects of isolation including stress, anxiety, and sedentarism, all of which further reduces immunity and increases non-communicable disease risk. EXPERT OPINION: Improving host immunity and mitigating the negative effects of isolation via physical activity is strongly justified. Exercise should be done in moderate intensities and volumes during the current pandemic, which is a nutritionally, psychologically, socially challenging environment in the presence of a virulent viral organism. Proactively creating innovative health promotion models with technology and government involvement with the best available evidence should be encouraged to reduce physical inactivity during the current COVID-19 pandemic and after.

Aging, Male Sex, Obesity, and Metabolic Inflammation Create the Perfect Storm for COVID-19.

Coronavirus disease 2019 (COVID-19) is a novel threat that seems to result from the collusion between a new pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and an existing pandemic of metabolic disease driven by obesity. This Perspective explores the evolving epidemiological, clinical, biological, and molecular evidence to propose an unfolding paradigm in which old age, chronic metabolic disease (such as obesity, type 2 diabetes, and metabolic syndrome), and male biological sex produce a deadly symbiosis of dysregulated immunometabolism and chronic systemic inflammation that intensifies virally induced hyperinflammation associated with SARS-CoV-2 infection. It is intended to inspire new research directions and stimulate funding in this field.