Rare Variants in Cardiomyopathy Genes Predispose to Cardiac Injury in Severe COVID-19 Patients of African or Hispanic Ancestry

Overview

Journal J Mol Med (Berl)

Specialty General Medicine

Date 2024 Dec 28

PMID 39730912

Authors

Hui-Qi Qu

Matthew S Delfiner

Chethan Gangireddy

Anjali Vaidya

Kenny Nguyen

Isaac R Whitman

JuFang Wang

Jianliang Song

Michael R Bristow

Charles F McTiernan

Glenn S Gerhard

Hakon Hakonarson

Arthur M Feldman

Affiliations

Soon will be listed here.

Abstract

In one of the earliest reports from China during COVID-19, it was noted that over 20% of patients hospitalized with the disease had significant elevations of troponin, a marker of myocardial tissue damage, that put them at a higher risk. In a hypothesis-independent whole exome sequencing (WES) study in hospitalized COVID-19 patients of diverse ancestry, we observed putative enrichment in pathogenic variants in genes known to be involved in the pathogenesis of cardiomyopathy. This observation led us to hypothesize that the observed high morbidity and mortality in these patients might be due to the presence of rare genetic factors that had previously been silent but became relevant as a consequence of the severe stress inflicted by an infection with SARS-CoV-2. To test this hypothesis, we analyzed our WES data generated from a cohort of 325 patients sequentially admitted for COVID-19 infection. In this predominantly minority population (53.9% African ancestry and 37.9% Hispanic/Latin ancestry), our initial analysis screen identified 263 variants that were identified as highly deleterious (HD) from a total of 26,661 variants of interest that represented 215 genes. Of those, we identified 46 genes (in 58 patients) harboring rare HD coding variants that were previously implicated in dilated cardiomyopathy and were considered as disease initiators for the severe COVID-19 in this study. These findings offer valuable insights into the molecular mechanisms and genetic susceptibility to heart injury in severe COVID-19. KEY MESSAGES: COVID-19 may cause cardiac damage in some affected patients without a plausible biological explanation. Our study reveals an enrichment of highly deleterious variants linked to cardiomyopathy in severe COVID-19 patients. Genetic profiling unveils the molecular basis of severe COVID-19-related heart injury, potentially aiding in patient stratification.

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