SARS-CoV-2-related immune dysregulation and biologically plausible pathways to lymphomagenesis: a PRISMA-ScR-based scoping review.

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related immune dysregulation has generated interest in diagnostic pathology because infection-related inflammation, long coronavirus disease (COVID)-related immune disturbance, and post-vaccination lymphoid reactions may overlap with lymphoid-biological mechanisms and complicate the distinction between reactive lymphoid proliferations and lymphoid neoplasia.

AIM: This scoping review aimed to map biologically plausible pathways through which SARS-CoV-2-associated immune perturbation may intersect with lymphomagenesis-related mechanisms, emphasizing diagnostic implications rather than causality.

MATERIALS AND

METHODS

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed∕MEDLINE, Scopus, and Web of Science were searched from January 2020 to March 2026, with selected pre-2020 sources retained for mechanistic or diagnostic relevance. Sources were charted across mechanistic, immunological, virological, clinicopathological, and diagnostic domains.

RESULTS

After screening and eligibility assessment, 63 sources were retained for thematic synthesis. Evidence clustered around lymphoma-relevant but non-specific mechanisms, including inflammatory signaling, impaired immune surveillance, latent oncogenic viral reactivation, prolonged germinal-center activity with activation-induced cytidine deaminase (AID)-related genomic vulnerability, and lymphoid microenvironment remodeling. These mechanisms appear most relevant in predisposed hosts with chronic immune dysregulation, latent viral infection, defective deoxyribonucleic acid (DNA) repair, or occult abnormal lymphoid clones. Infection and vaccination are distinct contexts, because infection may produce broader immune disruption, whereas most post-vaccination nodal events are reactive and self-limited.

CONCLUSIONS

Current evidence supports biological plausibility rather than a direct or generalizable causal relationship. The main diagnostic implication is careful clinicopathological correlation and distinction between reactive lymphoid proliferations and lymphoid neoplasia in post-COVID-19 and post-vaccination settings.