Novel insights into diagnosis and management of hyperreactivity: a narrative review

Hyperreactivity (HR) refers to an exaggerated biological response to a given stimulus that is within the normal physiological range, resulting from a lowered activation threshold of the involved system or effector cells. It commonly occurs after surgery, lung transplantation, and coronavirus disease 2019 (COVID-19) infection but lacks a unified concept and systematic understanding. This review aims to elucidate the concept, mechanisms, and disease spectrum of HR as an independent clinical entity, systematically explore its roles in postoperative conditions, lung transplantation, and COVID-19, and develop a biomarker-based hierarchical management framework, thereby providing a new paradigm for its precise recognition and intervention.

We systematically searched the PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure databases for literature published from January 1, 1968, to November 1, 2025, including reviews, randomized controlled trials, and observational studies, human or animal studies related to HR mechanisms or clinical phenotypes, while excluding non-peer-reviewed materials such as case reports and conference abstracts.

This study first proposes that HR arises from a four-dimensional imbalance across the nervous, endocrine, immune, and microenvironmental systems, characterized by thoroughness, early onset/persistence, and individual variability. The mechanisms underlying HR in postoperative, transplant-related, and COVID-19 conditions are systematically summarized, and a hierarchical, biomarker-based management framework is developed, highlighting the need for marker validation and trajectory modeling.

HR represents an independent clinical entity that transcends traditional disease boundaries. This review provides a new paradigm for its precise recognition and intervention and is expected to advance the conceptual and practical development of this field. Future research, clinical practice, and policy formulation should be individualized and mechanism-driven.