Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 11:9:821162.
doi: 10.3389/fcvm.2022.821162. eCollection 2022.

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

Kyle Varkoly  1   2 , Shaoyuan Tan  3 , Roxana Beladi  2   4 , David Fonseca  2 , Isabela Rivabem Zanetti  2 , Simona Kraberger  5 , Chintan Shah  6 , Jordan R Yaron  2   7 , Liqiang Zhang  2 , Michael Juby  2 , Ayman Fath  8 , Sriram Ambadapadi  2 , Melanie House  8 , Paul Maranian  2 , Carl J Pepine  9 , Arvind Varsani  5   9 , Jan Moreb  10 , Stacey Schultz-Cherry  3 , Alexandra R Lucas  2   9   11
Affiliations

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

Kyle Varkoly et al. Front Cardiovasc Med. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Bar graphs demonstrating mean LVEF ± SE with chemotherapy. No significant change in LVEF, as assessed by ANOVA, was detected for treatments with dexamethasone (A), revlimid (B), lenolidomide (C), bortezomib (D), cyclophosphamide (E), cancer diagnosed (F), or gender (G). Simple regression analysis demonstrates a significant correlation between LVEF post chemotherapy and increased age (H).
Figure 2
Figure 2
RNA virus sequence reads detected in blood samples demonstrated no significant association for orthomyxovirus (A), paramyxovius (B) nor retrovirus (C) with bortezomib or with dexamethasone for detected paramyxovirus reads (D). Bortezomib chemotherapy was associated with a trend toward detection of all paramyxo-, orthomyxo- and retro-virus sequences detected (E). Analysis for virus detection with gender (F, ANOVA) and age (G, simple regression analysis) detected no significant changes.
Figure 3
Figure 3
An initial rigorous analysis for detected virus sequences in blood samples with reduced LVEF detected no significant correlation. Analysis of paramyxovirus (A) orthomyxovirus (B) or total combined paramyxovirus and orthomyxovirus (C) sequences detected no significant correlation on simple regression analysis.
Figure 4
Figure 4
A secondary broad analysis demonstrated a correlation between paramyxovirus bidirectional sequence reads with LVEF pre and post chemotherapy, but with greater correlation and significance post chemotherapy LVEF (A). Similar correlations were detected for orthomyxovirus both pre and post chemotherapy (B). Retrovirus reads had no detectable correlation with LVEF pre chemotherapy, but a trend to increased correlation post chemotherapy (C). Analysis of all RNA virus reads for paramyxovirus, orthomyxovirus and retrovirus reads detected a significant correlation for changes in LVEF post chemotherapy (D).
Figure 5
Figure 5
Other virus sequences detected on the broader platform for RNA viruses demonstrated no significant correlations between viral sequence reads and LVEF post chemotherapy; Molivirus (A), Pandora virus (B), Panderina fiscellaria nucleopolyhedrovirus (C), Proteus (D), Pseudomonas phage (E) and Streptomyces (F) phage.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Chang H-M, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management-Part 1. J Am Coll Cardiol. (2017) 70:2536–51. 10.1016/j.jacc.2017.09.1096 - DOI - PMC - PubMed
    1. Stoltzfus KC, Zhang Y, Sturgeon K, Sinoway LI, Trifiletti DM, Chinchilli VN, et al. . Fatal heart disease among cancer patients. Nat Comm. (2020) 11:1–8. 10.1038/s41467-020-15639-5 - DOI - PMC - PubMed
    1. Yeh ETH, Ewer MS, Moslehi J, Dlugosz-Danecka M, Banchs J, Chang HM, et al. . Mechanisms clinical course of cardiovascular toxicity of cancer treatment I. Oncol Semin Oncol. (2019) 46:397–402. 10.1053/j.seminoncol.2019.10.006 - DOI - PubMed
    1. Morrison VA. Immunosuppression associated with novel chemotherapy agents and monoclonal antibodies. Clin Inf Dis. (2014) 59:S360–4. 10.1093/cid/ciu592 - DOI - PubMed
    1. Nesher L, Rolston KV. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection. (2014) 42:5–13. 10.1007/s15010-013-0525-9 - DOI - PubMed