Pathogenesis of SARS-CoV-2 induced cardiac injury from the perspective of the virus

Background Coronavirus disease 2019 (COVID-19) has high infectivity and causes extensive morbidity and mortality. Cardiovascular disease is a risk factor for adverse outcomes in COVID-19, but baseline left ventricular ejection fraction (LVEF) in particular has not been evaluated thoroughly in this context. Methods We analyzed patients in our state's largest health system who were diagnosed with COVID-19 between March 20 and May 15, 2020. Inclusion required an available echocardiogram within one year prior to diagnosis. The primary outcome was all-cause mortality. LVEF was analyzed both as a continuous variable and using a cutoff of 40%. Results Among 396 patients (67±16 years, 191 [48%] male, 235 [59%] Black, 59 [15%] LVEF ≤40%), 289 (73%) required hospital admission, and 116 (29%) died during 85±63 days of follow-up. Echocardiograms, performed a median of 57 (IQR 11-122) days prior to COVID-19 diagnosis, showed a similar distribution of LVEF between survivors and decedents (p=0.84). Receiver operator characteristic analysis revealed no predictive ability of LVEF for mortality, and there was no difference in survival among those with LVEF ≤40% vs. >40% (p=0.49). Multivariable analysis did not change these relationships. Similarly, there was no difference in LVEF based on whether the patient required hospital admission (56±13 vs. 55±13, p=0.38), and patients with a depressed LVEF did not require admission more frequently than their preserved-LVEF peers (p=0.87). A premorbid history of dyspnea consistent with symptomatic heart failure was not associated with mortality (p=0.74). Conclusions Among patients diagnosed with COVID-19, pre-COVID-19 LVEF was not a risk factor for death or hospitalization.

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“…Direct cytotoxic damage may also play a role. ( 16 ) Several cases of COVID-related fulminant myocarditis have been reported. ( 17 , 18 , 19 )…”

Section: Discussionmentioning

confidence: 99%

Impact of Preinfection Left Ventricular Ejection Fraction on Outcomes in COVID-19 Infection

Morin

Manzo²,

Pantlin

et al. 2021

Current Problems in Cardiology

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“…ACE2, a key part of the renin–angiotensin–aldosterone system (RAAS), which is thought to facilitate cellular coronaviruses entry ( Ziegler et al, 2020 ), leading to myocardial damage, endothelial and microvascular dysfunction, plaque vulnerability, and MI ( Guzik et al, 2020 ). The possible mechanisms of myocardial damage caused by COVID-19 infection are as follows: (1) direct injury: viral infection can directly cause damage to myocardial cells ( Knowlton, 2020 ); (2) immune injury: The resulting over-activation of the immune system produces an extreme immune response and releases a large amount of cytokines ( Java et al, 2020 ; Wiersinga et al, 2020 ). In addition, the promotion of immune system dysregulation occurs during the distribution of blood pressure, suggesting another mechanism connecting arterial hypertension and COVID-19.…”

Section: Introductionmentioning

confidence: 99%

A meta-meta-analysis: Evaluation of meta-analyses published in the effectiveness of cardiovascular comorbidities on the severity of COVID-19

et al. 2021

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“…11 It remains unclear whether this potentially dangerous cardiac involvement is the result of direct virus replication in the heart or secondary cardiac injury in the context of hypoxia, thrombosis, and multi-organ damage. 12 To reveal cardiac infection with SARS-CoV-2 and associated pathological consequences, myocardial tissue was investigated directly in our studies. 11 To address (i) the extent of virus infection and replication within the myocardial tissue, (ii) the virus localization in the heart and (iii) changes of gene expression associated with cardiac SARS-CoV-2 infection, we performed a systematic analysis of hearts obtained at autopsy from deceased who died with SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiac SARS-CoV-2 infection is associated with distinct transcriptomic changes within the heart

Lindner

Braeuninger

Stoffers

et al. 2020

Preprint

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1AbstractBackgroundAnalyses in hospitalized patients and small autopsy series suggest that severe SARS-CoV-2 infection may affect the heart. We investigated heart tissue by in situ hybridization, immunohistochemistry and RNA sequencing in consecutive autopsy cases to quantify virus load and characterize cardiac involvement in COVID-19.MethodsLeft ventricular tissue from 95 deceased with diagnosed SARS-CoV-2 infection undergoing autopsy was analyzed and clinical data were collected. RNA was isolated to examine virus load of SARS- CoV-2 and its replication in the heart. A virus load >1000 copies per µg RNA was defined as relevant. Viral RNA and inflammatory cells were assessed using histology. RNA sequencing and gene ontology (GO) enrichment were performed in 10 cases with high cardiac virus load and 10 age-matched cases without cardiac infection.ResultsA relevant SARS-CoV-2 virus load was detected in 41 out of 95 deceased (43%). The median cardiac virus load was 7952 copies per µg RNA (IQR 2507, 32 005). In situ hybridization revealed SARS- CoV-2 RNA primarily in the interstitium or interstitial cells. Virus detection was not associated with increased inflammatory cells. Relevant cardiac infection was associated with increased expression of the entry factor TMPRSS2. Cardiac virus replication was found in 14/95 hearts (15%). Remarkably, cardiac virus replication was associated with shorter time between diagnosis and death. RNA sequencing revealed clear activation of immune response pathways to virus infection and destruction of cardiomyocytes. Hearts with high virus load showed activation of the GO term “extracellular exosomes”.ConclusionSARS-CoV-2 infection including virus replication and distinct transcriptomic alterations without signs of myocarditis demonstrate a cardiac involvement. In this autopsy series, cardiac replication of SARS-CoV-2 was associated with early death.

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Pathogenesis of SARS-CoV-2 induced cardiac injury from the perspective of the virus

Cited by 33 publications

References 62 publications

Impact of Preinfection Left Ventricular Ejection Fraction on Outcomes in COVID-19 Infection

Impact of Preinfection Left Ventricular Ejection Fraction on Outcomes in COVID-19 Infection

A meta-meta-analysis: Evaluation of meta-analyses published in the effectiveness of cardiovascular comorbidities on the severity of COVID-19

Cardiac SARS-CoV-2 infection is associated with distinct transcriptomic changes within the heart

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