biostudies-literatureEggenhuizen PJMonash HealthMonash Health Foundation COVID-19 Research FundAustralian Government Research Training Program (RTP) scholarshipAustralian Government564https://www.ebi.ac.uk/biostudies/studies/S-EPMC10967880biostudies-literatureUnknown12(3)Memory T cells form from the adaptive immune response to historic infections or vaccinations. Some memory T cells have the potential to recognise unrelated pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and generate cross-reactive immune responses. Notably, such T cell cross-reactivity has been observed between SARS-CoV-2 and other human coronaviruses. T cell cross-reactivity has also been observed between SARS-CoV-2 variants from unrelated microbes and unrelated vaccinations against influenza A, tuberculosis and measles, mumps and rubella. Extensive research and debate is underway to understand the mechanism and role of T cell cross-reactivity and how it relates to Coronavirus disease 2019 (COVID-19) outcomes. Here, we review the evidence for the ability of pre-existing memory T cells to cross-react with SARS-CoV-2. We discuss the latest findings on the impact of T cell cross-reactivity and the extent to which it can cross-protect from COVID-19.BiomedicinesThe Influence of Cross-Reactive T Cells in COVID-19.PMC10967880NAResearch Training ProgramEggenhuizen PJOoi JDfalseThe Influence of Cross-Reactive T Cells in COVID-19.Memory T cells form from the adaptive immune response to historic infections or vaccinations. Some memory T cells have the potential to recognise unrelated pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and generate cross-reactive immune responses. Notably, such T cell cross-reactivity has been observed between SARS-CoV-2 and other human coronaviruses. T cell cross-reactivity has also been observed between SARS-CoV-2 variants from unrelated microbes and unrelated vaccinations against influenza A, tuberculosis and measles, mumps and rubella. Extensive research and debate is underway to understand the mechanism and role of T cell cross-reactivity and how it relates to Coronavirus disease 2019 (COVID-19) outcomes. Here, we review the evidence for the ability of pre-existing memory T cells to cross-react with SARS-CoV-2. We discuss the latest findings on the impact of T cell cross-reactivity and the extent to which it can cross-protect from COVID-19.2024-01-01T00:00:00Z2024 Mar2025-04-21T21:30:57.359Z2025-04-05T18:22:24.955ZS-EPMC109678803854017810.3390/biomedicines12030564