A Broader View of COVID
By Aine Cryts
Radiology Today
Vol. 22 No. 4 P. 14

COVID-19 drives cross-specialty collaboration and insight into subclinical findings.

The FDA has provided emergency use authorization for three COVID-19 vaccinations, as of the writing of this article. That’s while President Joseph Biden has worked in concert with state governors to streamline access to vaccines. As of April 19, 2021, every adult in the country is eligible for a vaccine, ahead of President Biden's goal of May 1. Currently, more than one-quarter of the United States’ population has been fully vaccinated. Meanwhile, the Centers for Disease Control and Prevention continues to provide guidance related to vaccinated adults and maintaining social distancing as well as other public health measures to prevent the spread of the virus that has claimed more than 567,000 lives in the United States and in excess of 3 million lives around the world.

But flashback to March 2020. At the start of the pandemic, which was declared by the World Health Organization on March 11, 2020, the operating assumption was that COVID-19 was a respiratory virus. That was after the virus claimed its first reported US fatality in Seattle on February 6, according to the Center for Infectious Disease Research and Policy at the University of Minnesota. In June 2020, STAT reported that it wasn’t clear at first to clinicians about how the coronavirus could “wreak havoc from head to toe.”

To come were scenes of health care workers in protective equipment, their faces temporarily marked from wearing N95 masks at hospitals in New York, Italy’s Lombardy region, and cities and towns around the world. These health care workers were treating patients with a variety of illnesses that impacted the gastrointestinal, respiratory, neurological, and other systems.

A key in the scientific and medical journey to understanding the virus was the discovery of the role of angiotensin-converting enzyme 2 (ACE2), a protein that resides in cell membranes of the lungs, arteries, heart, kidney, and intestines. The protein invites the coronavirus and allows it to infect cells throughout the body.

Yuchi Han, MD, an associate professor of medicine and radiology and director of cardiac MRI at the University of Pennsylvania’s Perelman Center for Advanced Medicine in Philadelphia, says radiologists and all physicians need to be aware that the consequences of COVID-19 are “very widespread.” Han encourages physicians to investigate abnormalities and symptoms in organ systems that may have occurred due to COVID-19 infections.

Subclinical Findings on MRI
Han is a coauthor of a prospective longitudinal study published in Radiology in January that revealed MRI-derived extracellular volume fraction and 2D global longitudinal strain may be markers of cardiac involvement among patients who have recovered from COVID-19; these are patients without cardiac symptoms or clinical findings of myocardial injury. This was a single-center, observational study performed at No. 2 People’s Hospital of Fuyang City in Anhui, China; it includes recovered patients who were seen in follow-up clinics between May and September 2020.

According to the study, 24 of the 40 participants, all of whom had recovered from moderate or severe COVID-19, had extracellular volume fraction, which is used to measure the severity of myocardial injury. A confirmed case with fever, respiratory symptoms, and radiographic evidence of pneumonia is defined as a moderate case; a severe case is defined as a moderate case with dyspnea or respiratory failure.

The patients experienced no cardiac symptoms or cardiac abnormalities, according to researchers. There was evidence of subclinical changes of myocardial dysfunction with lower left ventricular 2D global longitudinal strain among 28 of the patients included in the study, regardless of the severity of pneumonia they experienced.

Han explains that one of the lessons from the study is that subclinical findings, such as myocardial dysfunction, can be significant in multiple organ systems with COVID-19; in this case, with the cardiovascular system. Still, she says that the “implication of all of this is to be determined, but we should be aware that [subclinical or clinical findings] are there.”

Until COVID-19 transformed the world, viral illness hadn’t been closely studied in the context of cardiology or cardiology imaging, Han says. What’s unknown is the impact of the subclinical findings on long-term cardiology-specific outcomes for patients, but it’s a question Han wants to answer because of the real-world impact on patients. Beyond COVID-19, Han sees this as an opportunity to understand viral illness and its implications on the heart.

“Most of the time, as a cardiologist, we see people who come in years later who have dilated cardiomyopathy [where] we couldn’t really figure out the reason, and I know some reports say maybe 50% of those were the result of a viral illness in the past,” she says. A disease of the heart muscle, dilated cardiomyopathy typically starts in the left ventricle and can range from having no symptoms to being life-threatening. According to the Mayo Clinic, it’s a common cause of heart failure and most often occurs in men between 20 and 50 years of age. It’s possible that unrecognized and untreated viral illness could have a negative result decades later.

“That would be a little bit on the late side because, when [patients] present with [dilated cardiomyopathy], it really influences their mortality,” she says.

Sequences that are commercially available on MRI scanners, such as phase-sensitive inversion-recovery gradient echo, late gadolinium enhancement (LGE), and myocardial mapping, were used in the study. For the myocardial mapping sequences, researchers only used T 1 sequences; T 2 sequences are used for edema, which usually goes away in three to six months, Han explains.

That’s relevant, Han points out, because during the early days of the pandemic, in March and April 2020, health care providers often opted not to image patients during their acute disease, due to the fear of infection. This limited a full understanding of the acute illness, but she credits health care providers with being more likely to image patients during the current stage of the pandemic.

“We realize that many [infections] can be mitigated by practicing exactly what has been recommended, in terms of masks and eye shields and other personal protective gear,” Han says. That’s helpful because more patients are being successfully imaged during their acute illness or right after their acute illness, she adds.

Cross-Specialty Collaboration
Precisely because COVID-19 can impact more than one bodily system, Xiaohu Li, MD, an associate professor in the department of radiology at the First Affiliated Hospital of Anhui Medical University in Hefei, China, cites the study in Radiology, of which he was a coauthor, as evidence of scholarship between radiologists and cardiologists.

Han agrees, and she sees a “silver lining” of the pandemic: Namely, increased collaboration among researchers across the world, which has occurred at a much greater degree and much more quickly than before the pandemic. “I think the scientific community [was] really mobilized to address these issues on a global scale. That has been very interesting and very encouraging,” she adds.

At the beginning of the pandemic, there was a “lack of information,” Han says. The need for real-time information about COVID-19 led to a “flood of preprints,” many of which were written by nonexperts and unvetted by the scientific community, she explains. For example, in her research to develop a literature review about the virus last April, she found many low-quality articles that were potentially misleading. The reality that inaccurate information about COVID-19 was made available in many preprint articles reinforced for Han the value of the critical peer-review process in the scientific community.

According to RSNA News, Radiology had received more than 500 papers related to COVID-19 by the end of March 2020. By way of contrast, during a typical month, the journal receives 250 papers across the entire specialty.

While the review cycle prior to the pandemic typically took about six months from submission to publication, David Bluemke, MD, PhD, editor of Radiology, wanted to abbreviate the timeline. In response, the journal’s editorial board developed a new process for immediate triage of all articles related to COVID-19. That meant an article was reviewed within 12 to 24 hours. In collaboration with the editorial team at the online journal Radiology: Cardiothoracic Imaging, relevant papers about COVID-19 are reviewed and returned to authors for review within two days of submission. Most authors can respond within 24 hours, which means the articles are often published online within a day of final acceptance, according to RSNA News. Most articles are available online within three to seven days of submission, and key articles are available in Chinese and Farsi. Notably, all resources related to COVID-19 are available for free.

“With members in more than 130 countries around the world, RSNA has a responsibility to ensure that its COVID-19 research and education is available to help guide members and other physicians caring for patients during this rapidly evolving medical crisis,” Jeffrey S. Klein, MD, RSNA board liaison for publications and communications and editor of RadioGraphics, told RSNA News.

RSNA also hosts a COVID-19 Resources webpage that curates original research, images, and commentaries related to the virus. Radiologists on Li’s team at the First Affiliated Hospital of Anhui Medical University relied on these resources to diagnose and manage suspected patients.

— Aine Cryts is a health care writer based in the Boston area.