Integrative Multidimensional Profiling of Individuals Recovered from Mild COVID-19 Reveals Immune–Metabolic–Oxidative Network Interactions
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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-metabolic 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.
DOI: 10.3390/ijms27146518
Authors: Iole Macchia, Valentina La Sorsa, Francesca Marcon, Cristina Andreoli, Alessandro Giuliani, Donatella Pietraforte, Maria Cristina Quattrini, Egidio Iorio, Mattea Chirico, Maria Elena Pisanu, Enrica Montefiore, Francesca Luciani, Antonio Martina, Fabiola Mancini, Martina Borghi, Valentina Durastanti, Maria Concetta Altavista, Francesca Urbani
Institutions: Istituto Superiore di Sanità, ASL Roma, Ospedale San Filippo Neri
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: Istituto Superiore di Sanità
Award: G8409986131
OpenAlex ID: W7170080935
