TY - JOUR
T1 - RNA Virus Gene Signatures Detected in Patients With Cardiomyopathy After Chemotherapy; A Pilot Study
AU - Varkoly, Kyle
AU - Tan, Shaoyuan
AU - Beladi, Roxana
AU - Fonseca, David
AU - Zanetti, Isabela Rivabem
AU - Kraberger, Simona
AU - Shah, Chintan
AU - Yaron, Jordan R.
AU - Zhang, Liqiang
AU - Juby, Michael
AU - Fath, Ayman
AU - Ambadapadi, Sriram
AU - House, Melanie
AU - Maranian, Paul
AU - Pepine, Carl J.
AU - Varsani, Arvind
AU - Moreb, Jan
AU - Schultz-Cherry, Stacey
AU - Lucas, Alexandra R.
N1 - Funding Information:
This work was supported by Biodesign, ASU startup funding (AL), American Heart Association (AL), National Institutes of Health (AL), and St Jude Children's Research Hospital (SS-C).
Publisher Copyright:
Copyright © 2022 Varkoly, Tan, Beladi, Fonseca, Zanetti, Kraberger, Shah, Yaron, Zhang, Juby, Fath, Ambadapadi, House, Maranian, Pepine, Varsani, Moreb, Schultz-Cherry and Lucas.
PY - 2022/3/11
Y1 - 2022/3/11
N2 - Background: Viral infections are pervasive and leading causes of myocarditis. Immune-suppression after chemotherapy increases opportunistic infections, but the incidence of virus-induced myocarditis is unknown. Objective: An unbiased, blinded screening for RNA viruses was performed after chemotherapy with correlation to cardiac function. Methods: High-throughput sequencing of RNA isolated from blood samples was analyzed following chemotherapy for hematological malignancies (N = 28) and compared with left ventricular ejection fraction (LVEF). Results: On initial rigorous analysis, low levels of influenza orthomyxovirus and avian paramyxovirus sequences were detectable, but without significant correlation to LVEF (r = 0.208). A secondary broad data mining analysis for virus sequences, without filtering human sequences, detected significant correlations for paramyxovirus with LVEF after chemotherapy (r = 0.592, P < 0.0096). Correlations were similar for LVEF pre- and post- chemotherapy for orthomyxovirus (R = 0.483, P < 0.0421). Retrovirus detection also correlated with LVEF post (r = 0.453, p < 0.0591), but not pre-chemotherapy, but is suspect due to potential host contamination. Detectable phage and anellovirus had no correlation. Combined sequence reads (all viruses) demonstrated significant correlation (r = 0.621, P < 0.0078). Reduced LVEF was not associated with chemotherapy (P = NS). Conclusions: This is the first report of RNA virus screening in circulating blood and association with changes in cardiac function among patients post chemotherapy, using unbiased, blinded, high-throughput sequencing. Influenza orthomyxovirus, avian paramyxovirus and retrovirus sequences were detectable in patients with reduced LVEF. Further analysis for RNA virus infections in patients with cardiomyopathy after chemotherapy is warranted.
AB - Background: Viral infections are pervasive and leading causes of myocarditis. Immune-suppression after chemotherapy increases opportunistic infections, but the incidence of virus-induced myocarditis is unknown. Objective: An unbiased, blinded screening for RNA viruses was performed after chemotherapy with correlation to cardiac function. Methods: High-throughput sequencing of RNA isolated from blood samples was analyzed following chemotherapy for hematological malignancies (N = 28) and compared with left ventricular ejection fraction (LVEF). Results: On initial rigorous analysis, low levels of influenza orthomyxovirus and avian paramyxovirus sequences were detectable, but without significant correlation to LVEF (r = 0.208). A secondary broad data mining analysis for virus sequences, without filtering human sequences, detected significant correlations for paramyxovirus with LVEF after chemotherapy (r = 0.592, P < 0.0096). Correlations were similar for LVEF pre- and post- chemotherapy for orthomyxovirus (R = 0.483, P < 0.0421). Retrovirus detection also correlated with LVEF post (r = 0.453, p < 0.0591), but not pre-chemotherapy, but is suspect due to potential host contamination. Detectable phage and anellovirus had no correlation. Combined sequence reads (all viruses) demonstrated significant correlation (r = 0.621, P < 0.0078). Reduced LVEF was not associated with chemotherapy (P = NS). Conclusions: This is the first report of RNA virus screening in circulating blood and association with changes in cardiac function among patients post chemotherapy, using unbiased, blinded, high-throughput sequencing. Influenza orthomyxovirus, avian paramyxovirus and retrovirus sequences were detectable in patients with reduced LVEF. Further analysis for RNA virus infections in patients with cardiomyopathy after chemotherapy is warranted.
KW - LVEF
KW - RNA
KW - cancer
KW - cardiomyopathy
KW - chemotherapy
KW - immune suppression
KW - infection
KW - virus
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U2 - 10.3389/fcvm.2022.821162
DO - 10.3389/fcvm.2022.821162
M3 - Article
AN - SCOPUS:85138514526
SN - 2297-055X
VL - 9
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 821162
ER -