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- Title
Adaptive Metabolic and Inflammatory Responses Identified Using Accelerated Aging Metrics Are Linked to Adverse Outcomes in Severe SARS-CoV-2 Infection.
- Authors
Márquez-Salinas, Alejandro; Fermín-Martínez, Carlos A; Antonio-Villa, Neftalí Eduardo; Vargas-Vázquez, Arsenio; Guerra, Enrique C; Campos-Muñoz, Alejandro; Zavala-Romero, Lilian; Mehta, Roopa; Bahena-López, Jessica Paola; Ortiz-Brizuela, Edgar; González-Lara, María Fernanda; Roman-Montes, Carla M; Martinez-Guerra, Bernardo A; Leon, Alfredo Ponce de; Sifuentes-Osornio, José; Gutiérrez-Robledo, Luis Miguel; Aguilar-Salinas, Carlos A; Bello-Chavolla, Omar Yaxmehen; C Guerra, Enrique; Ponce de Leon, Alfredo
- Abstract
<bold>Background: </bold>Chronological age (CA) is a predictor of adverse coronavirus disease 2019 (COVID-19) outcomes; however, CA alone does not capture individual responses to severe acute respiratory syndrome coronavirus 2 (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.<bold>Method: </bold>In this retrospective cohort study, we assessed cases admitted to a COVID-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 (intensive care unit 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.<bold>Results: </bold>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 < .001). Using unsupervised clustering, we identified 4 adaptive responses to SARS-CoV-2 infection: (i) inflammaging associated with CA, (ii) metabolic dysfunction associated with cardiometabolic comorbidities, (iii) unfavorable hematological response, and (iv) response associated with favorable outcomes.<bold>Conclusions: </bold>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.
- Subjects
MEXICO City (Mexico); COVID-19; SARS-CoV-2; COVID-19 pandemic; INFLAMMATION; PROPORTIONAL hazards models
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2021, Vol 76, Issue 8, pe117
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glab078