The Nova Protocol: A Comprehensive Multimodal Longitudinal Study among Civilian Survivors of a Mass Trauma Event

<jats:p>Background: The October 7, 2023 attack in southern Israel was one of the deadliest terror attacks in modern history, with 1,182 fatalities, more than 4,000 wounded individuals, and 251 hostages. The Nova music festival, an all-night outdoor rave near the Gaza border, suffered the highest number of civilian casualties, with more than 370 festival attendees killed. Survivors were exposed to prolonged life-threatening trauma with similar characteristics and within a narrow time window. Many survivors also reported being under the acute influence of psychoactive substances during the attack and the following hours. This tragic combination of civilian mass trauma and naturalistic pharmacological exposure created a rare opportunity to study trauma processing prospectively. Objective: This paper describes the rationale, design, and methodology of the Nova Protocol, a multimodal longitudinal observational study of survivors of the October 7, 2023 Nova festival attack and a sociocultural comparison group. Methods: The protocol spans from the first weeks to approximately 24 months post-trauma and includes three major assessment time points. It integrates repeated online clinical assessments, prolonged wearable-sensor monitoring, ecological assessments, saliva-based endocrine and inflammatory markers, structural and functional MRI, cardiac interoception paradigms, online and in-scanner reinforcement-learning tasks, and semi-structured qualitative interviews. Primary outcomes are PTSD symptom severity (PCL-5) and general psychological distress (K6), supplemented by a rich battery of secondary measures. Conclusion: The Nova Protocol provides an unusually rich longitudinal framework for characterizing psychological, behavioral, physiological, inflammatory, neural, interoceptive, and subjective mechanisms that shape clinical trajectories after civilian mass trauma. Because psychoactive substance exposure was naturalistic and self-selected, findings will be interpreted as mechanistic and prognostic associations rather than causal effects. The protocol is expected to inform early risk detection and scalable post-disaster monitoring and intervention strategies, as well as unique insights into how psychoactive substances impact trauma processing.</jats:p>