Adaptive metabolic and inflammatory responses identified using accelerated aging metrics are linked to adverse outcomes in severe SARS-CoV-2 infection

Alejandro Márquez-Salinas, Carlos A Fermín-Martínez, Neftalí Eduardo Antonio-Villa, Arsenio Vargas-Vázquez, Enrique C. Guerra, Alejandro Campos-Muñoz, Lilian Zavala-Romero, Roopa Mehta, Jessica Paola Bahena-López, Edgar Ortiz-Brizuela, María Fernanda González-Lara, Carla M Roman-Montes (+6 others)
2021 The journals of gerontology. Series A, Biological sciences and medical sciences  
Background Chronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Methods In this retrospective cohort study, we assessed cases admitted to a
more » ... VID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.
doi:10.1093/gerona/glab078 pmid:33721886 fatcat:w3ufcngsifevlbgwh75qh6lmdi