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. 2023 Feb;45(1):543-553.
doi: 10.1007/s11357-022-00666-5. Epub 2022 Oct 3.

Age-dependent association of clonal hematopoiesis with COVID-19 mortality in patients over 60 years

Marta Del Pozo-Valero  1   2 , Marta Corton  1   2 , Rosario López-Rodríguez  1   2   3 , Ignacio Mahillo-Fernández  4 , Javier Ruiz-Hornillos  5   6 , Pablo Minguez  1   2   7 , Cristina Villaverde  1   2 , María Elena Pérez-Tomás  8 , María Barreda-Sánchez  8   9 , Esther Mancebo  10   11 ; STOP_Coronavirus Study Group; Estela Paz-Artal  10   12   13 , Encarna Guillén-Navarro  2   8   14   15 , Berta Almoguera  1   2 , Carmen Ayuso  16   17
Collaborators, Affiliations

Age-dependent association of clonal hematopoiesis with COVID-19 mortality in patients over 60 years

Marta Del Pozo-Valero et al. Geroscience. 2023 Feb.

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.

Keywords: COVID-19; Clonal variants; Mortality risk.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Mutational landscape of clonal variants in our cohort of COVID-19 patients. A Histogram representing the number of clonal variants per gene in the 19 genes where clonality was present. B Violin plots of VAF (y-axis) representing the distribution of variant allele frequencies (VAF) for clonal variants for the five most frequently mutated genes
Fig. 2
Fig. 2
Clonality in COVID-19 patients. Frequency of CH in the entire cohort was stratified by age (A), presence (B) and the number of CHIP variants (C) in deceased patients and survivors in the same age groups
Fig. 3
Fig. 3
Odds ratios obtained by logistic regression for the association between CH and mortality of COVID-19 in our cohort, stratifying by age and adjusted by sex, ethnicity, obesity, cardiovascular disease, hypertension, and diabetes. Cardiovascular disease includes the following pre-existing conditions: ischemic heart disease, heart failure, cardiac arrhythmia and peripheral vascular disease. “Clonality” refers to the presence of clonal variants and “clonal variants” indicates the total number of clonal variants. In the association of clonality with age, age is introduced as a continuous predictor, and in the association between mortality and clonality, clonality is a dichotomous variable. Clonal variants, P/LP variants, VUS variants, and VAF are introduced as continuous predictors
See this image and copyright information in PMC

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