COVID-lateral damage: cardiovascular manifestations of SARS-CoV-2 infection

Al‐Kindi, Sadeer; Zidar, David A.

doi:10.1016/j.trsl.2021.11.005

Cited by 8 publications

(8 citation statements)

References 191 publications

(163 reference statements)

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“…Additionally, our analyses of the humoral response to vaccination revealed that myopericarditis patients generated typical or even lower SARS-CoV-2 specific antibodies and neutralizing antibody responses relative to healthy vaccinated controls, consistent with previous results ( 40 ). These patients also did not show evidence of cardiac-targeted autoantibodies, which have been reported in SARS-CoV-2 infection ( 83 – 85 ), in agreement with observations reported from one patient ( 32 ). While anti-IL-1RA antibodies have been reported in some patients from another report ( 80 ), analysis of non-cardiac antigens in a subset of patients from our cohort showed no such autoantibodies ( 86 ).…”

Section: Discussionsupporting

confidence: 91%

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis

et al. 2023

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Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2–specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1β, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3 + cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2 + CD163 + monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell–associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine–-associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

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Section: Discussionsupporting

confidence: 91%

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis

et al. 2023

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“…Finally, in full agreement with the “multifactorial” definition of COVID-19 association with cardiac injury and multi-organ thrombo-inflammation [ 9 ], besides the imaging abnormalities and the systemic metabolic perturbations (e.g., hyper-inflammation and immuno-thrombosis), we will need to focus translational research and clinical trials to novel emerging laboratory biomarkers, such as circulating histones, which may induce multi-organ deleterious effects, explaining SARS-CoV-2 tropism and helping to refine cardiovascular and systemic risk stratification along with clinical management of COVID-19 patients [ 29 , 50 ] ( Figure 1 ).…”

supporting

confidence: 60%

“…Several studies shed light on the crucial interplay among inflammation, thrombosis, cardiovascular diseases, multi-visceral manifestations, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, namely linking the roles of neutrophil extracellular traps (NETs), nucleosomes, histones, cytokines, and the coagulation cascade [ 1 , 2 , 3 , 4 , 5 ]. A possible novel association of coronavirus disease 2019 (COVID-19) with cardiovascular risk, heart attack, and stroke has also been underpinned [ 6 , 7 ], thus suggesting an urgent need to explore the biomolecular characteristics of such an increased risk of developing cardiovascular events in patients with SARS-CoV-2 infection [ 8 , 9 ].…”

mentioning

confidence: 99%

Do Circulating Histones Represent the Missing Link among COVID-19 Infection and Multiorgan Injuries, Microvascular Coagulopathy and Systemic Hyperinflammation?

Ligi

Maniscalco

Plebani

et al. 2022

JCM

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Several studies shed light on the interplay among inflammation, thrombosis, multi-organ failures and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Increasing levels of both free and/or circulating histones have been associated to coronavirus disease 2019 (COVID-19), enhancing the risk of heart attack and stroke with coagulopathy and systemic hyperinflammation. In this view, by considering both the biological and clinical rationale, circulating histones may be relevant as diagnostic biomarkers for stratifying COVID-19 patients at higher risk for viral sepsis, and as predictive laboratory medicine tool for targeted therapies.

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“…Studies to date suggest that the underlying pathophysiology of COVID-19-associated cardiac injury may be multi-factorial, as it can derive from both systemic perturbations (hyper-inflammation and thrombophilia) and potential direct cardiotoxic effects of SARS-CoV-2 due to disruption of the renin-angiotensin system, microangiopathy via endothelial cell/pericyte involvement (akin to parvovirus), or cardiomyocyte damage [40].…”

Section: Covid-19 and Thrombosismentioning

confidence: 99%

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review

Abrignani

Murrone

Luca

et al. 2022

JCM

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The coronavirus disease 2019 (COVID-19), a deadly pandemic that has affected millions of people worldwide, is associated with cardiovascular complications, including venous and arterial thromboembolic events. Viral spike proteins, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary means for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently located in the cerebral venous sinus but also splanchnic, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting anti-platelet factor-4 antibodies activating platelets. For this reason, the regulatory agencies of various countries restricted the use of adenovirus-based vaccines to some age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19, including thrombotic complications, clearly outweighs this potential risk. This point-of-view aims at providing a narrative review of epidemiological issues, clinical data, and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping medical practitioners to offer up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic cardiovascular thrombotic events.

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COVID-lateral damage: cardiovascular manifestations of SARS-CoV-2 infection

Cited by 8 publications

References 191 publications

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis

Do Circulating Histones Represent the Missing Link among COVID-19 Infection and Multiorgan Injuries, Microvascular Coagulopathy and Systemic Hyperinflammation?

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review

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