SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations

doi:10.1016/j.jare.2025.05.013

Journal of Advanced Research

Available online 10 May 2025

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https://doi.org/10.1016/j.jare.2025.05.013 Get rights and content

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Open access

Highlights

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Our investigation provides histopathological and electron microscopic analyses from endomyocardial biopsies of five Long COVID patients.
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Electron microscopy revealed widespread mitochondrial disorder and the presence of myofilament degradation.
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Similar mitochondria disorganization were found in SARS-CoV-2 infected mice.
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Proteomic profiling indicated that the most significantly changed genes and proteins are related to mitochondrial structure and function.

Abstract

Introduction

With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored.

Objectives

Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as “Long COVID”, which has significantly affected millions globally.

Methods

We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, palpitation, chest tightness, and acute myocarditis.

Results

All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID.

Conclusion

Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.

Graphical abstract

Keywords

Long COVID

SARS-COV-2

Endomyocardial biopsy

Mitochondria disorder

Abbreviations

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

COVID-19

coronavirus disease 2019

MACE

major adverse cardiac events

CPR

cardiopulmonary resuscitation

AED

automated external defibrillator

ECG

electrocardiogram

CMR

cardiac magnetic resonance

CAG

coronary angiography

Echo

echocardiography

hematoxylin-eosin

cTnT

cardiac troponin T

OMM

outer mitochondrial membrane

IMM

inner mitochondrial membrane

FIB-SEM

focused ion beam scanning-electron microscopy

DEPs

differentially expressed proteins

KEGG

Kyoto Encyclopedia of Genes and Genomes

TOM

translocase of the outer mitochondrial membrane

TIM

translocase of the inner mitochondrial membrane

SAM

sorting and assembly machinery

mtDNA

mitochondrial DNA

Cited by (0)

¹: These authors contributed equally.