Cardiovascular risks of COVID-19 antivirals

Emerging evidence reveals that COVID-19 antiviral therapies may pose severe cardiovascular risks, urging caution in treating vulnerable patients.

Study: Cardiovascular adverse effects of antiviral therapies for COVID-19: Evidence and plausible mechanisms. Image Credit: Corona Borealis Studio / Shutterstock.com

Several antivirals, including remdesivir, Paxlovid, molnupiravir, and monoclonal antibodies like tixagevimab and cilgavimab, have been repurposed to treat the coronavirus disease 2019 (COVID-19) or received emergency use authorization (EUA). Antimalarial and antiparasitic drugs like ivermectin, hydroxychloroquine, and chloroquine have also been investigated for their potential activity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

A recent review published in the journal Acta Pharmacologica Sinica discusses the cardiovascular adverse effects associated with antiviral drugs used to treat COVID-19.

About the virus

SARS-CoV-2 is a single-stranded ribonucleic acid (RNA) virus enclosed in a protein envelope comprising the membrane, spike, and envelope proteins. Viral RNA is stored within the nucleocapsid, comprised of the nucleocapsid protein.

The SARS-CoV-2 spike protein recognizes and subsequently binds to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cell. The S1 subunit of the spike protein consists of an N-terminal domain (NTD) and receptor-binding domain (RBD).

RBD-ACE2 binding causes the S2 subunit to dissociate from the ACE2 molecule, which subsequently causes the virus to transition from a pre to post-fusion state. Thereafter, the virus and host cell membranes fuse together, thereby allowing viral entry into the cell.

ACE2 and cardiovascular adverse effects

ACE2 regulates the vasoactive effects of ACE, which converts angiotensin I to angiotensin II, a potent vasoconstrictor and pro-inflammatory agent. Angiotensin II induces hyperinflammation due to the dysregulated release of cytokines, leading to severe tissue damage and multi-organ failure, which is often characteristic of severe COVID-19.

Pre-pandemic antivirals and cardiovascular effects

Idoxuridine was the first antiviral approved in 1963 for feline herpesvirus-1 eye infections; since then, 37 antivirals have been approved to treat a wide range of infections caused by the human immunodeficiency virus (HIV), hepatitis B virus (HBV), cytomegalovirus (CMV), influenza virus, respiratory syncytial virus (RSV), and hepatitis C virus (HCV).

Among the drugs used to treat HIV include protease inhibitors like lopinavir/ritonavir, which increase lipid levels in the blood, liver, and heart, in addition to weakening heart pumping activity. Endothelial damage has also been observed, which may cause atherosclerosis with its cardiovascular sequelae. Interferon-α, which is used in the treatment of multiple viral infections and cancers, has also been associated with adverse cardiac effects.

Remdesivir

Remdesivir is a prodrug that converts to an analog of the nucleotide adenosine, thereby disrupting viral replication. The vasodilation activity of adenosine can induce the release of catecholamines like epinephrine, thereby increasing the risk of ventricular tachycardia, ventricular fibrillation, and atrial fibrillation.

When administered intravenously, remdesivir can trigger QT prolongation and the potentially deadly arrhythmia torsade de pointes. Thus, continuous heart monitoring is essential for COVID-19 patients being treated with remdesivir, especially those with pre-existing cardiac disease or electrolyte abnormalities.

Paxlovid

Paxlovid, which consists of nirmatrelvir and ritonavir, may cause bradycardia and sinus dysfunction. However, it remains unclear which component of Paxlovid is responsible and what mechanisms are involved in this adverse side effect.

The toxicity of Paxlovid, when combined with tacrolimus, an immunosuppressant, has been reported in several cases. Paxlovid may also increase the risk of bleeding when used in combination with ticagrelor, warfarin, or rivaroxaban.

Paxlovid may also interact with other drugs to cause skeletal muscle breakdown and myopathy.

Molnupiravir

Esterases in host plasma activate molnupiravir to its active antiviral nucleoside analog EIDD-1931. Molnupiravir can increase oxidant stress, which may cause tissue damage. However, like Paxlovid, the use of molnupiravir can reduce the risk of severe COVID-19, particularly among those with diabetes and patients 65 years of age and older.

Other drugs

Hydroxychloroquine (HCQ) acidifies intracellular endosomes and affects the viral life cycle at multiple stages. Its therapeutic effects may be synergistic with those of azithromycin.

Nevertheless, both HCQ and azithromycin can cause prolonged QTc or cardiac arrhythmias. Thus, the combination of these drugs may not be ideal for severe COVID-19 or patients at an increased risk of QT prolongation.

Ivermectin

Ivermectin inhibits interactions between the virus and host cell, thereby preventing nuclear transport of viral proteins. However, preclinical data suggests the accumulation of ivermectin in the heart and inhibition of potassium currents. Patients with COVID-19 who are treated with ivermectin should be monitored for arrhythmias or QT prolongation.

Antibodies

Both monoclonal antibodies (mAbs) and plasma have been used to treat COVID-19. Cardiac arrhythmias have been reported with mAb, particularly following treatment with tixagevimab or cilgavimab.

The combination of cilgavimab and tocilizumab may cause thromboembolic events. Hypertension is most commonly reported with mAbs like casirivimab and imdevimab, bamlanivimab alone or with etesevimab, and sotrovimab.

Conclusions

The potential cardiovascular side effects of COVID-19 therapeutics must be carefully considered before prescribing these agents to high-risk patients. Despite reported observations of cardiotoxicity, additional studies are needed to differentiate the cardiovascular effects of SARS-CoV-2 infection from those of antivirals.

Future antiviral drug development assisted with the newest artificial intelligence platform may improve the accuracy to predict the structures of biomolecules of antivirals and therefore to mitigate their associated cardiovascular adversities.”

Journal reference:
  • Chen, E., & Xi, L. (2024). Cardiovascular adverse effects of antiviral therapies for COVID-19: Evidence and plausible mechanisms. Acta Pharmacologica Sinicadoi:10.1038/s41401-024-01382-w.
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Thomas, Liji. (2024, September 18). Cardiovascular risks of COVID-19 antivirals. News-Medical. Retrieved on October 05, 2024 from https://www.news-medical.net/news/20240916/Cardiovascular-risks-of-COVID-19-antivirals.aspx.

  • MLA

    Thomas, Liji. "Cardiovascular risks of COVID-19 antivirals". News-Medical. 05 October 2024. <https://www.news-medical.net/news/20240916/Cardiovascular-risks-of-COVID-19-antivirals.aspx>.

  • Chicago

    Thomas, Liji. "Cardiovascular risks of COVID-19 antivirals". News-Medical. https://www.news-medical.net/news/20240916/Cardiovascular-risks-of-COVID-19-antivirals.aspx. (accessed October 05, 2024).

  • Harvard

    Thomas, Liji. 2024. Cardiovascular risks of COVID-19 antivirals. News-Medical, viewed 05 October 2024, https://www.news-medical.net/news/20240916/Cardiovascular-risks-of-COVID-19-antivirals.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Cardiovascular risks post-COVID-19 vaccination: Key findings