Age-dependent association of clonal hematopoiesis with COVID-19 mortality in patients over 60 years
Authors: Del Pozo-Valero Marta , Corton Marta , López-Rodríguez Rosario , Mahillo-Fernández Ignacio , Ruiz-Hornillos Javier , Minguez Pablo , Villaverde Cristina , Pérez-Tomás María Elena , Barreda-Sánchez María , Mancebo Esther ,   the STOP_Coronavirus Study Group, Fernández-Caballero Lidia , Sanchez Ruth Fernández , Vara Inés García , Gordo Laura Marzal , Martínez-Ramas Andrea , Ondo Lorena , Romero Raquel , Górgolas Miguel , Cabello Alfonso , Barba Germán Peces , Heili Sara , Calvo César , Santos Arnoldo , Ríos María Dolores Martín , Sánchez-Pernaute Olga , Llanos Lucía , Zazo Sandra , Rojo Federico , Villar Felipe , de Andrés Raimundo , Alfaro Ignacio Jiménez , Gadea Ignacio , Perales Celia , Herrero Antonio , Taracido Juan Carlos , García-Vázquez Elisa , Jara-Rubio Rubén , Pons-Miñano José A. , Marín-Martínez Juana María , Herranz-Marín María Teresa , Bernal-Morell Enrique , García-García Josefina , de Dios González-Caballero Juan , Chirlaque-López María Dolores , Minguela-Puras Alfredo , Muro-Amador Manuel , Moreno-Docón Antonio , Yagüe-Guirao Genoveva , Abellán-Perpiñán José M. , Martínez-Pérez Jorge E. , Sánchez-Martínez Fernando I. , Utrero-Rico Alberto , Fernández-Ruiz Mario , Carretero Octavio , Aguado José María , Laguna-Goya Rocío , Juárez Yolanda Cañadas , Jiménez Ángel , Abián María Herrera , Salmones Mercedes García , Alarcon Lidia Gagliardi , Oliveira María Rubio , Romero Carlos Fabian Castaño , Cosgaya Carlos Aranda , Palomares Virginia Víctor , Rodríguez Leticia García , Abad María Sánchez Carpintero , Torrejón María Carmen García , Paz-Artal Estela , Guillén-Navarro Encarna , Almoguera Berta , Ayuso Carmen 
Published: October 2022

Abstract
Clonal hematopoiesis, especially that of indeterminate potential (CHIP), has been associated with age-related diseases, such as those contributing to a more severe COVID-19. Four studies have attempted to associate CHIP with COVID-19 severity without conclusive findings. In the present work, we explore the association between CHIP and COVID-19 mortality. Genomic DNA extracted from peripheral blood of COVID-19 patients (n = 241 deceased, n = 239 survivors) was sequenced with the Myeloid Solutions™ panel of SOPHiA Genetics. The association between clonality and age and clonality and mortality was studied using logistic regression models adjusted for sex, ethnicity, and comorbidities. The association with mortality was performed with patients stratified into four groups of age according to the quartiles of the distribution: 60–74 years, 75–84 years, 85–91 years, and 92–101 years. Clonality was found in 38% of the cohort. The presence of CHIP variants, but not the number, significantly increased with age in the entire cohort of COVID-19 patients, as well as in the group of survivors (p < 0.001). When patients were stratified by age and the analysis adjusted, CHIP classified as pathogenic/likely pathogenic was significantly more represented in deceased patients compared with survivors in the group of 75–84 years (34.6% vs 13.7%, p = 0.020). We confirmed the well-established linear relationship between age and clonality in the cohort of COVID-19 patients and found a significant association between pathogenic/likely pathogenic CHIP and mortality in patients from 75 to 84 years that needs to be further validated.