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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The COVID-19 pandemic underscored the need to better characterize immune and molecular responses following SARS-CoV-2 infection and vaccination. Beyond antibody and cellular immunity, COVID-19 involves oxidative stress and DNA damage, affecting repair mechanisms and metabolic adaptation linked to immune resilience. Here, we present a multidimensional analysis of 20 individuals who recovered from mild COVID-19, integrating clinical features with humoral and cellular immune responses, T cell and myeloid phenotypes, oxidative stress, DNA damage, and metabolomic and lipidomic profiles. Although most individual parameters fell within physiological ranges, network modeling revealed structured associations spanning multiple biological domains. A central finding was a coherent cluster organized around vaccine dose number, linking anti-Spike antibody titers, oxidative stress, bioenergetic signatures, and granulocyte activation. Higher vaccination was associated with stronger humoral responses, lower oxidative stress, and a more balanced myeloid\u2013metabolic profile, suggesting a potential protective role extending beyond antibody induction. Additional associations linked symptom patterns to T cell differentiation states, anti-nucleocapsid responses to systemic inflammation, and anaerobic signatures to DNA damage markers, revealing interconnections between immunometabolism, clinical expression, and genomic stress. Despite the small sample size, these findings offer a preliminary systems-level perspective on mild COVID-19 recovery and illustrate the value of integrative exploratory frameworks in infectious disease research, laying the groundwork for validation in larger longitudinal cohorts.<\/jats:p>","DOI":"10.3390\/ijms27146518","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:25:46Z","timestamp":1784726746000},"page":"6518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Multidimensional Profiling of Individuals Recovered from Mild COVID-19 Reveals Immune\u2013Metabolic\u2013Oxidative Network Interactions"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3870-8202","authenticated-orcid":false,"given":"Iole","family":"Macchia","sequence":"first","affiliation":[{"name":"Oncology and Molecular Medicine Department, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"La Sorsa","sequence":"additional","affiliation":[{"name":"Research Promotion and Coordination Service, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-8310","authenticated-orcid":false,"given":"Francesca","family":"Marcon","sequence":"additional","affiliation":[{"name":"Environment and Health Department, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3724-0668","authenticated-orcid":false,"given":"Cristina","family":"Andreoli","sequence":"additional","affiliation":[{"name":"Environment and Health Department, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-804X","authenticated-orcid":false,"given":"Alessandro","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Independent Researcher, 00183 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6370-912X","authenticated-orcid":false,"given":"Donatella","family":"Pietraforte","sequence":"additional","affiliation":[{"name":"Core Facilities, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Quattrini","sequence":"additional","affiliation":[{"name":"Core Facilities, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6673-3838","authenticated-orcid":false,"given":"Egidio","family":"Iorio","sequence":"additional","affiliation":[{"name":"Core Facilities, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-5077","authenticated-orcid":false,"given":"Mattea","family":"Chirico","sequence":"additional","affiliation":[{"name":"Core Facilities, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Pisanu","sequence":"additional","affiliation":[{"name":"Core Facilities, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3508-3892","authenticated-orcid":false,"given":"Enrica","family":"Montefiore","sequence":"additional","affiliation":[{"name":"Core Facilities, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-2808","authenticated-orcid":false,"given":"Francesca","family":"Luciani","sequence":"additional","affiliation":[{"name":"National Center for the Control and Evaluation of Medicines, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Martina","sequence":"additional","affiliation":[{"name":"National Center for the Control and Evaluation of Medicines, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Mancini","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6313-0273","authenticated-orcid":false,"given":"Martina","family":"Borghi","sequence":"additional","affiliation":[{"name":"Infectious Disease Department, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Durastanti","sequence":"additional","affiliation":[{"name":"Neurology Unit, San Filippo Neri Hospital, Rome 1 Local Health Authority (ASL RM1), 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concetta","family":"Altavista","sequence":"additional","affiliation":[{"name":"Neurology Unit, San Filippo Neri Hospital, Rome 1 Local Health Authority (ASL RM1), 00135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-2706","authenticated-orcid":false,"given":"Francesca","family":"Urbani","sequence":"additional","affiliation":[{"name":"Oncology and Molecular Medicine Department, National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ramasamy, R. 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