NEW YORK (Reuters Health) – Myocardial inflammation in SARS-CoV-2 patients is likely characterized by activation of the mitogen-activated protein kinase (MAPK) pathway and a complement cascade, a proteomic analysis of a small case series suggests.
“In (COVID-19) patients, myocardial inflammation has previously been characterized using clinical imaging and histology,” Dr. Ludwig Weckbach and Dr. Christian Schulz, both of Ludwig Maximilian University Hospital in Munich told Reuters Health by email.
“In this work, we provide a proof-of-concept for the analysis of paraffin-embedded myocardial tissue by proteomics, (which) provides additional information on the molecular phenotype that is associated with this condition (and) could facilitate research into various forms of cardiomyopathies,” they said.
“We are intrigued by the upregulation of the complement pathway in viral infections, including COVID-19,” they added. “However, our work requires confirmation in prospective studies with larger numbers of patients.”
As reported in JAMA Cardiology, the team analyzed cardiac tissue obtained by biopsy from 19 patients with suspected myocarditis (median age, 58; 79%, men; no data on race/ethnicity), including five (median age, 64; 80%, men) who were hospitalized with SARS-CoV-2 infection between March-May 2020.
Specimens from those five patients were compared with previously collected specimens from five patients with immune-mediated myocarditis, four with non-SARS-CoV-2 viral myocarditis, and five with noninflammatory cardiomyopathy (controls).
Inflammatory cardiac phenotypes were measured by immunohistologic analysis, RNA exome capture sequencing, and mass spectrometry-based proteomic analysis.
T-cell abundance generally was higher in the cardiac tissue of patients with non-SARS-CoV-2-associated myocarditis (virus-associated or immune-mediated). By contrast, lymphocyte counts were lower in the tissue of patients with SARS-CoV-2 infection.
Although scavenger receptor CD163 expression increased in patients with all inflammatory conditions compared with those in the noninflammatory control group, macrophages in the SARS-CoV-2 group had the highest median fluorescence intensity values.
Further, in those with SARS-CoV-2 infection, components of the complement cascade that belonged to the most commonly upregulated transcripts and differentially abundant proteins included C1q subunits (transcriptomic analysis: 2.5- to 3.6-fold increase; proteomic analysis: 2.0- to 3.4-fold increase) and serine/cysteine proteinase inhibitor clade G member 1 (transcriptomic analysis: 1.7-fold increase; proteomic analysis: 2.6-fold increase).
Additionally, the abundance of C1q was highest in cardiac macrophages in SARS-CoV-2 infection, and serine/threonine MAPK pathways were upregulated.
The authors conclude, “The present study provides proof of concept for multimodal analysis of cardiac (formalin-fixed paraffin-embedded) biopsy material, which may improve the diagnosis and treatment of heart diseases in the future.”
Dr. Anuradha Lala-Trindade, a cardiologist at The Mount Sinai Hospital in New York City, commented in an email to Reuters Health, “Observations of cardiovascular manifestations of COVID-19 have prompted extensive inquiry as to underlying mechanisms of viral entry and injury of the myocardium.”
“Because endomyocardial biopsies are not routinely performed in the setting of suspected or confirmed myocarditis attributed to SARS-CoV-2 infection, understanding of the biologic underpinnings as to how the virus specifically leads to injury has been limited,” she said.
The current study “found histopathologic and molecular profiles that may be unique to SARS-CoV-2,” she noted. “These findings are…exploratory and require confirmation, but are incremental in advancing our knowledge as to markers unique to SARS-CoV-2 infection that may be therapeutic targets. Such detailed reports will hopefully will provide a platform for further research into understanding the mechanism of this injury.”
SOURCE: https://bit.ly/3ecAzYI JAMA Cardiology, online December 15, 2021.
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