RNA Virus Gene Signatures Detected in Patients With Cardiomyopathy After Chemotherapy; A Pilot Study

Kyle Varkoly; Shaoyuan Tan; Roxana Beladi; David Fonseca; Isabela Rivabem Zanetti; Simona Kraberger; Chintan Shah; Jordan R Yaron; Liqiang Zhang; Michael Juby; Ayman Fath; Sriram Ambadapadi; Melanie House; Paul Maranian; Carl J Pepine; Arvind Varsani; Jan Moreb; Stacey Schultz-Cherry; Alexandra R Lucas

doi:10.3389/fcvm.2022.821162

RNA Virus Gene Signatures Detected in Patients With Cardiomyopathy After Chemotherapy; A Pilot Study

Front Cardiovasc Med. 2022 Mar 11:9:821162. doi: 10.3389/fcvm.2022.821162. eCollection 2022.

Authors

Kyle Varkoly^{1

2}, Shaoyuan Tan³, Roxana Beladi^{2

4}, David Fonseca², Isabela Rivabem Zanetti², Simona Kraberger⁵, Chintan Shah⁶, Jordan R Yaron^{2

7}, Liqiang Zhang², Michael Juby², Ayman Fath⁸, Sriram Ambadapadi², Melanie House⁸, Paul Maranian², Carl J Pepine⁹, Arvind Varsani^{5

9}, Jan Moreb¹⁰, Stacey Schultz-Cherry³, Alexandra R Lucas^{2

9

11}

Affiliations

¹ Department of Internal Medicine, McLaren Macomb Hospital- Michigan State University College of Human Medicine, Mt Clemens, MI, United States.
² Center for Personalized Diagnostics, The Biodesign Institute, Arizona State University, Tempe, AZ, United States.
³ Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States.
⁴ Department of Neurological Surgery, Ascension Providence Hospital- Michigan State University College of Human Medicine, Southfield, MI, United States.
⁵ The Biodesign Center of Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, United States.
⁶ Division of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, FL, United States.
⁷ School for Engineering of Matter, Transport and Energy, Ira A. Fulton Schools of Engineering, Arizona State University, Tempe, AZ, United States.
⁸ Department of Internal Medicine, Dignity Health, Creighton University, Phoenix, AZ, United States.
⁹ Division of Cardiology, Department of Medicine, University of Florida, Gainesville, FL, United States.
¹⁰ Hematologic Malignancies, Transplantation and Cellular Therapy Program, Forsyth Medical Center, Derrick L Davis Cancer Center, Winston-Salem, NC, United States.
¹¹ Center for Immunotherapy, Vaccines and Virotherapy, The Biodesign Institute, Arizona State University, Tempe, AZ, United States.

Abstract

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.

Keywords: LVEF; RNA; cancer; cardiomyopathy; chemotherapy; immune suppression; infection; virus.