Pérez-Gómez, AlbertoGasca-Capote, CarmenVitallé, JoanaOstos, Francisco JSerna-Gallego, AnaTrujillo-Rodríguez, MaríaMuñoz-Muela, EsperanzaGiráldez-Pérez, TeresaPraena-Segovia, JuliaNavarro-Amuedo, María DPaniagua-García, MaríaGarcía-Gutiérrez, ManuelAguilar-Guisado, ManuelaRivas-Jeremías, InmaculadaJiménez-León, María ReyesBachiller, SaraFernández-Villar, AlbertoPérez-González, AlexandreGutiérrez-Valencia, AliciaRafii-El-Idrissi Benhnia, MohammedWeiskopf, DanielaSette, AlessandroLópez-Cortés, Luis FPoveda, EvaRuiz-Mateos, EzequielVirgen del Rocío Hospital COVID-19 and COHVID-GS Working Teams2023-05-032023-05-032022http://hdl.handle.net/10668/21873SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study, we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with the absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalised and previously hospitalised patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalised patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors' samples. These results could have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/COVID-19IL-2SARS-CoV-2SpikeT-cell responseendemic coronavirusesnucleocapsidpolyfunctionalityCOVID-19HumansImmunoglobulin GImmunologic MemoryInterleukin-2SARS-CoV-2Severity of Illness IndexT-LymphocytesDeciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response.research article35415890open access10.1002/ctm2.8022001-1326PMC9005926https://doi.org/10.1002/ctm2.802https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005926/pdf