To stress or not to stress: Brain-behavior-immune interaction may weaken or promote the immune response to SARS-CoV-2

Abstract

The COVID-19 pandemic continues to strongly affect people with health disadvantages, creating a heavy burden on medical systems and societies worldwide. Research is growing rapidly and recently revealed that stress-related factors such as socio-economic status, may also play a pivotal role. However, stress research investigating the underlying psychoneuroimmune interactions is missing. Here we address the question whether stress-associated neuroendocrine-immune mechanisms can possibly contribute to an increase in SARS-CoV-2 infections and influence the course of COVID-19 disease. Additionally, we discuss that not all forms of stress (e.g. acute versus chronic) are detrimental and that some types of stress could attenuate infection-risk and -progression. The overall aim of this review is to motivate future research efforts to clarify whether psychosocial interventions have the potential to optimize neuroendocrine-immune responses against respiratory viral infections during and beyond the COVID-19 pandemic. The current state of research on different types of stress is summarized in a comprehensive narrative review to promote a psychoneuroimmune understanding of how stress and its mediators cortisol, (nor)adrenaline, neuropeptides and neurotrophins can shape the immune defense against viral diseases. Based on this understanding, we describe how people with high psychosocial stress can be identified, which behaviors and psychosocial interventions may contribute to optimal stress management, and how psychoneuroimmune knowledge can be used to improve adequate care for COVID-19 and other patients with viral infections.

Keywords: (Nor)adrenaline; COVID-19; Hypothalamic-pituitary-adrenal axis; Immune activation; Immune suppression; Neuropeptide; Prevention; Stress; Stress reduction.

Fig. 1

The brain keeps close psychoneuroimmune contact with barrier-forming immune competent tissues such as bronchial, intestinal or cutaneous epithelia. This interaction enables constant interaction between the brain and the periphery, which can affect the control of viral infections of respective organs.

Fig. 2

Adaptive interaction of neuroendocrine-immune processes (left panel) transforms into maladaptive interactions in the presence of chronic stress (right panel).

Fig. 3

Psychological factors that exacerbate virus infection in a vicious circle. Psychosocial interventions may interfere with the exacerbation and thereby prevent or improve viral infection.