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AIM The COVID-19 crisis is affecting our sense of self and touches upon its existential fears. This extends to the self-other relationship as there is both being infected and infecting the other. What this pandemic crisis tells us about our self and relatedness, its cultural differences, and how these are rooted in the brain\'s relation to the world. METHODS First, we discuss about the psychological and neuronal features of self and and self-other relation and how they are rooted in a deeper layer of the brain\'s neural activity complemeting its cognitive surface layer. Secondly, we demonstrate cultural differences of eastern and western concepts of self, i.e., independency and inter-dependency, and how these reflect the manifestation of the brain\'s neuro-social and -ecological alignment. Finally, we highlight how inter-subjective and cultural nature of self surface in the COVID-19 crisis. RESULTS Discussing various lines of empirical data showing the brain\'s intimate alignment to both social and ecological environmental contexts our results support the assumption of the brain\'s deep layer features by laying bare a continuum of different degrees of neuro-social and neuro-ecological alignment. This entails a a two-stage model of self with neuro-social-ecological and psychological levels that extends the previously suggested basis model of self-specificity (BMSS). CONCLUSION We conclude that the current pandemic shows the importance of the deeper inter-subjective and cultural layers of both self and brain; their neglect can be life-threatening for self and others and, paradoxically, might reduce, rather than enlarge, the self\'s sense of freedom and independence. This article is protected by copyright. All rights reserved.
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