The spread of the SARSCov2 virus presents an unprecedented event that rapidly introduced widespread life threat, economic de-stabilization, and social isolation. The human nervous system is tuned to detect safety and danger, integrating body and brain responses via the autonomic nervous system. Polyvagal Theory provides a perspective to understand the impact of the pandemic on mental and physical health. This perspective highlights the important role of the state of the autonomic nervous system in exacerbating or dampening threat reactions to the pandemic. In addition, the theory alerts us to the impact of clinical history (e.g., trauma) on autonomic regulation as an important compounding risk factor lowering the threshold to behaviorally and physiologically destabilize in response to the pandemic. The theory provides a strategy to dampen the adverse reactions to threat (e.g., acute stress disorders) through portals of social engagement that evolved to downregulate defenses to promote calmness and connectedness.