From rare to more common: The emerging role of omics in improving understanding and treatment of severe inflammatory and hyperinflammatory conditions.

Inflammation is a pathogenic driver of many diseases, including atherosclerosis and rheumatoid arthritis. Hyperinflammation can be seen as any inflammatory response that is deleterious to the host, regardless of cause. In medicine, hyperinflammation is defined as severe, deleterious, and fluctuating systemic or local inflammation with presence of a cytokine storm. It has been associated with rare autoinflammatory disorders. However, advances in omics technologies, including genomics, proteomics, and metabolomics, have revealed it to be more common, occurring in sepsis and severe coronavirus disease 2019. With a focus on proteomics, this review highlights the key role of omics in this shift. Through an exploration of research, we present how omics technologies have contributed to improved diagnostics, prognostics, and targeted therapeutics in the field of hyperinflammation. We also discuss the integration of advanced technologies, multiomics approaches, and artificial intelligence in analyzing complex datasets to develop targeted therapies, and we address their potential for revolutionizing the clinical aspects of hyperinflammation. We emphasize personalized medicine approaches for effective treatments and outline challenges, including the need for standardized methodologies, robust bioinformatics tools, and ethical considerations regarding data privacy. This review aims to provide a comprehensive overview of the molecular mechanisms underpinning hyperinflammation and underscores the potential of omics technologies in enabling successful clinical management.