Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients

Abstract

A growing body of literature has emphasized the importance of biobehavioral processes - defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes - for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.

Keywords: Covid-19; biobehavioral; outcomes; stress; transplantation and cellular therapy.

Figure 1

Biobehavioral model illustrating Covid-19 impact for TCT patients. Biological processes affected by TCT, including inflammation and disrupted circadian rhythms, alter central nervous system pathways that evoke behavioral symptoms. Stress-related behavioral factors activate HPA and SNS axes and are associated with downstream immunologic and genomic alterations. The products of these pathways, as well as direct sympathetic innervation of the bone marrow microenvironment, can modulate immune recovery and inflammation, potentially influencing clinical outcomes following TCT. Behavioral factors also directly relate to quality of life and late effects. Stress and adversity associated with the Covid-19 pandemic can exacerbate biological and behavioral impacts of TCT and biobehavioral mechanisms associated with poorer clinical outcomes. Similarly, infection with SARS-CoV-2 can also adversely affect biobehavioral factors and relationships. The paper further considers the intersection of Covid-19 impacts and individual differences in risk and protective factors, including age, SES, caregiver status, and donor characteristics relevant to biobehavioral processes and TCT outcomes.