key: cord-0928770-aatdcda5
authors: Soni, Meshal; McGovern, Michelle; Jacob, Ron; Weiss, Richard; Adusumalli, Srinath; Litwin, Sheldon; Jagasia, Dinesh; Scherrer-Crosbie, Marielle
title: Ultrasound Enhancing Agents and associated adverse reactions: a potential connection to the COVID-19 vaccines?
date: 2021-10-07
journal: J Am Soc Echocardiogr
DOI: 10.1016/j.echo.2021.09.014
sha: e785c949dd2c4fe6d79474465bcfe81a93daba80
doc_id: 928770
cord_uid: aatdcda5

nan

Meshal Soni, Michelle McGovern, Ron Jacob, Richard Weiss, Srinath Adusumalli, Sheldon Litwin, Dinesh Jagasia, Marielle Scherrer-Crosbie

On April 22, 2021, the federal Food and Drug Administration (FDA) notified healthcare professionals that ultrasound enhancing agents (UEA) containing polyethylene glycol (PEG): Definity TM , Definity RT TM and Lumason TM , should not be administered to patients with known or suspected allergies to PEG, due to concerns for presumed Type I immediate hypersensitivity reactions. The FDA alert reported 11 anaphylactic reactions and 2 patient deaths after administration of UEA over a reported period of ten years. These agents contain PEG as a component either in the vehicle or as an inactive ingredient alone (Lumason TM ) or within the microbubble shell and lipid excipient (Definity TM , Definity RT TM ) [1, 2] . PEGs are commonly used in products including toothpaste, cosmetics, shampoo and in certain laxatives and bowel preparations as thickeners, solvents, softeners, and moisture carriers. [1] Recently, rare allergic reactions have been reported after administration of the Pfizer and Moderna Covid-19 vaccines. These mRNA vaccines have 'PEGylated' lipid nanoparticles for improved stability and delivery of mRNA into human cells. [3, 4] We write to inform your readers of adverse reactions after administration of Lumason TM Adverse reactions included shortness of breath, tongue and throat swelling, abdominal and back pain, hemodynamic instability, arrhythmias, and hypoxia. These adverse reactions were treated with antihistamines and/or steroids, along with supplemental oxygen, intravenous fluids and/or epinephrine or other vasopressors when oxygenation and hemodynamics were impacted. One patient experienced a cardiac arrest due to PEA after Lumason administration and was resuscitated. The 4 adverse reactions to Definity TM were reported in 2019, prior to the initiation of the COVID-19 vaccine program and occurred over a period of 4 months with 3 reactions occurring within the same month. The COVID-19 vaccination program commenced in December of 2020 after emergency use authorization was granted for the Pfizer and Moderna vaccines. [4] The 10 adverse reactions to Lumason TM at UPHS and MUSC (0.13% of total Lumason TM doses administered) were reported after January 1, 2021. Of the 10 patients with adverse reactions to Lumason TM , 6 patients were vaccinated (5 patients with Moderna, 1 patient with the Pfizer vaccine), 1 patient was unvaccinated and in 3 patients vaccination status could not be ascertained. The patient who was resuscitated after cardiac arrest was unvaccinated. These adverse reactions were reported to the UEA manufacturers. We have initiated efforts at UPHS to standardize documentation and reporting of these adverse reactions.

We agree with the expert ASE consensus statement (April 2021) that echocardiography laboratory personnel should be trained in the recognition and treatment of UEA related hypersensitivity reactions. [1] We write to your readers to report our institutional observations of a recent increase in adverse reactions to ultrasound enhancing agents notably prominent after January 2021 which coincided with the onset of the COVID-19 vaccination program. It is hypothesis generating but certainly not scientifically tested and confirmed that these observed adverse reactions may be potentially related to possible PEG sensitization after vaccination with the COVID-19 vaccines. We also fully acknowledge that the mechanism of these reported adverse reactions is unclear as to whether they were due to a Type I hypersensitivity reaction to PEG or due to immune mediated complement activation-related pseudoallergy (CARPA). [1] Given our institutional observations, it would be prudent for echocardiography laboratories to remain vigilant for detection of increased UEA related adverse reactions.

Expert Consensus Statement from the American Society of Echocardiography on Hypersensitivity Reactions to Ultrasound Enhancing Agents in Patients with Allergy to Polyethylene Glycol

Rare PEG Allergy Triggered Postvaccination Anaphylaxis

Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States