Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

Mustroph, Julian; Hupf, Julian; Baier, Maria J.; Evert, Katja; Brochhausen, Christoph; Broeker, Katharina; Meindl, Christine; Seither, Benedikt; Jungbauer, Carsten; Evert, Matthias; Maier, Lars S.; Wagner, Ştefan

doi:10.3389/fimmu.2021.740260

Cited by 18 publications

(15 citation statements)

References 46 publications

(58 reference statements)

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“…In our study, myocardial trichrome staining showed a significant increase in interstitial and perivascular fibrosis in both aerosol-infected and multi-route infected monkeys. This is in line with current reports [ 23 , 34 , 35 ]. At this time, there are no reports of co-staining fibrotic tissue with SARS-CoV-2 antibodies to demonstrate that fibrosis observed is due to the presence of virus particles at those specific areas in the myocardium.…”

Section: Discussionsupporting

confidence: 94%

Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model

Rabbani

Rappaport

Gupta

2022

Cells

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an extremely contagious disease whereby the virus damages the host’s respiratory tract via entering through the ACE2 receptor. Cardiovascular disorder is being recognized in the majority of COVID-19 patients; yet, the relationship between SARS-CoV-2 and heart failure has not been established. In the present study, SARS-CoV-2 infection was induced in the monkey model. Thereafter, heart tissue samples were collected, and pathological changes were analyzed in the left ventricular tissue by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to T lymphocytes and macrophages. The findings revealed that SARS-CoV-2 infection induces several pathological changes in the heart, which cause cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells, and hypertrophy. Furthermore, collagen-specific staining showed the development of cardiac fibrosis in the interstitial and perivascular regions in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. These findings suggest the progression of the disease, which can lead to the development of severe complications, including heart failure. Additionally, SARS-CoV-2 antigen staining detected the presence of virus particles in the myocardium. Thus, we found that SARS-CoV-2 infection is characterized by an exaggerated inflammatory immune response in the heart, which possibly contributes to myocardial remodeling and subsequent fibrosis.

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Section: Discussionsupporting

confidence: 94%

Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model

Rabbani

Rappaport

Gupta

2022

Cells

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“…Few case reports have demonstrated that SARS-CoV2 can immediately infect the myocardium, triggering viral myocarditis. Nevertheless, in the most cases, myocardial lesions are triggered by the rise in cardiometabolic request linked to systemic infection and continuous oxygen depletion induced by severe pneumonia [ 63 ]. This mechanism has been proposed and supports our results—the over expressions of ACE-2 receptors among the two diseased groups versus the healthy group.…”

Section: Discussionmentioning

confidence: 99%

“…These findings are in line with those of Mustroph et al who hypothesized that higher cardiac fibrosis may predispose to progression of severe COVID-19 due to increased cardiac expression of NRP-1, which permits viral cell entry. In addition, troponin I levels are elevated in severe COVID-19 cases [ 63 ]. Glinka et al and Meng et al concluded that the presence of soluble interleukin-1 receptor-like 1 (sIL1-RL1) in higher levels may provoke expression of NRP-1, the transforming growth factor β1 (TGF-β1) co-receptor [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

The Associations between Cytokine Levels, Kidney and Heart Function Biomarkers, and Expression Levels of Angiotensin-Converting Enzyme-2 and Neuropilin-1 in COVID-19 Patients

et al. 2022

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Background: Higher expression of angiotensin-converting enzyme-2 (ACE-2) in addition to neuropilin-1 (NRP-1) can lead to a cytokine storm which is correlated to higher mortality rate and contributes to the progression of renal diseases and the pathogenesis of coronary heart disease (CHD) in COVID-19 patients. Aim: We herein sought to examine correlations between cytokine levels, ACE-2 and NRP-1 expression, renal function biomarkers, and cardiac enzymes in COVID-19 patients. Patients and Methods: For the study, 50 healthy subjects and 100 COVID-19 patients were enrolled. Then, confirmed cases of COVID-19 were divided into two groups—those with moderate infection and those with severe infection—and compared to healthy controls. Serum creatinine, urea, CK-MB, LDH, troponin I, IL-1β, IL-4, IL-10, IL-17, and INF-γ levels were estimated. We also studied the gene expression for ACE-2 and NRP-1 in blood samples utilizing quantitative real-time polymerase chain reaction (qRT-PCR). Results: All COVID-19 patients demonstrated a significant increase in the levels of serum creatinine, urea, CK-MB, LDH, and troponin I, as well as examined cytokines compared to the healthy controls. Furthermore, ACE-2 mRNA and NRP-1 mRNA expression levels demonstrated a significant increase in both severe and moderate COVID-19 patient groups. In the severe group, serum creatinine and urea levels were positively correlated with IL-10, INF-γ, NRP-1, and ACE-2 expression levels. Moreover, LDH was positively correlated with all the examined cytokine, NRP-1, and ACE-2 expression levels. Conclusion: Deficits in renal and cardiac functions might be attributable to cytokine storm resulting from the higher expression of ACE-2 and NRP-1 in cases of COVID-19.

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“…Increased left ventricular strain as a fibrosis marker was found to predict moderate and severe COVID-19 progression with accuracy (96). Myocardial fibrogenesis is induced by transforming growth factor β1 (TGF-β1) (97, 98).…”

Section: Resultsmentioning

confidence: 99%

“…A recent study investigating a potential association between PON1 polymorphisms and COVID-19 pointed at a possible positive correlation between M55 and prevalence and mortality of COVID-19, although these findings remain to be validated in larger-scale studies (95). Increased left ventricular strain as a fibrosis marker was found to predict moderate and severe COVID-19 progression with accuracy (96). Myocardial fibrogenesis is induced by transforming growth factor β1 (TGF-β1) (97,98).…”

Section: Disease Ontologiesmentioning

confidence: 99%

Semantic and population analysis of the genetic targets related to COVID-19 and its association with genes and diseases

Papageorgiou

Papakonstantinou

Diakou

et al. 2022

Preprint

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SARS-CoV-2 is a coronavirus responsible for one of the most serious, modern worldwide pandemics, with lasting and multi-faceted effects. By late 2021, SARS-CoV-2 has infected more than 180 million people and has killed more than 3 million. The virus gains entrance to human cells through binding to ACE2 via its surface spike protein and causes a complex disease of the respiratory system, termed COVID-19. Vaccination efforts are being made to hinder the viral spread and therapeutics are currently under development. Towards this goal, scientific attention is shifting towards variants and SNPs that affect factors of the disease such as susceptibility and severity. This genomic grammar, tightly related to the dark part of our genome, can be explored through the use of modern methods such as natural language processing. We present a semantic analysis of SARS-CoV-2 related publications, which yielded a repertoire of SNPs, genes and disease ontologies. Population data from the 100Genomes Project were subsequently integrated into the pipeline. Data mining approaches of this scale have the potential to elucidate the complex interaction between COVID-19 pathogenesis and host genetic variation; the resulting knowledge can facilitate the management of high-risk groups and aid the efforts towards precision medicine.

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Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

Cited by 18 publications

References 46 publications

Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model

Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model

The Associations between Cytokine Levels, Kidney and Heart Function Biomarkers, and Expression Levels of Angiotensin-Converting Enzyme-2 and Neuropilin-1 in COVID-19 Patients

Semantic and population analysis of the genetic targets related to COVID-19 and its association with genes and diseases

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