Use of unproven COVID-19 therapies by African American patients poses risks

A common genetic marker in African Americans may predispose them to cardiac complications from COVID-19, and the use of therapies such as hydroxychloroquine may increase the risk – investigators urge caution in the journal Heart Rhythm


Philadelphia, June 15, 2020

Nearly one out of every 10 African Americans has a genetic variant that puts them inherently at an increased risk for ventricular arrhythmias and sudden cardiac death. Writing in the journal Heart Rhythm, the official publication of the Heart Rhythm Society and the Cardiac Electrophysiology Society, published by Elsevier, investigators observe that along with socioeconomic and cultural factors, this genetic risk factor may contribute to the racial health disparities that have been documented in victims of the COVID-19 pandemic. They also note that the unwanted effects of therapies such as hydroxychloroquine may put African Americans with the variant at increased risk of drug-induced ventricular arrhythmias. Therefore, they urge particular caution.

“Without a definitive explanation for the increased COVID 19-related mortality rates observed among individuals of African descent, we need to consider all potential contributors, including the possibility of genetic predispositions,” explained first author John R. Giudicessi, MD, PhD, Department of Cardiovascular Medicine (Clinician-Investigator Training Program and Division of Heart Rhythm Services), Mayo Clinic, Rochester, MN, USA. “The African-specific p.Ser1103Tyr-SCN5A common ion channel variant is a reasonable place to start, as its proarrhythmic potential is awakened by risk factors observed in hospitalized COVID-19 patients – namely, hypoxemia, electrolyte abnormalities, and QT-prolonging drug use.”

The investigators note that the proarrhythmic potential associated with p.Ser1103Tyr-SCN5A can be enhanced by drugs that can cause irregular heartbeat (QTc-prolonging medications), including some antiarrhythmic drugs but also, importantly, some antibiotics and antifungal medications.

Direct and/or indirect myocardial injury or stress has emerged as a prominent, prognostic feature in COVID-19. Acute myocardial injury in patients with COVID-19 may be caused by a direct SARS-CoV-2 myocardial infection; the exaggerated immune response known as the cytokine storm; or hypoxia, dangerously low levels of oxygen and high levels of carbon dioxide in the blood. African American infants with the p.Ser1103Tyr-SCN5A variant are over-represented in sudden infant death syndrome, and mechanisms underlying hypoxia may be responsible. The profound hypoxia observed in many COVID-19 patients, raises reasonable concern that p.Ser1103Tyr-SCN5A could produce a similar, African-American susceptibility to ventricular arrhythmia and sudden cardiac death from the SARS-CoV-2 infection.

Taken together, the data suggest that one in 13 African Americans may be at substantially increased risk for potentially lethal ventricular arrhythmia during the COVID-19 pandemic. Whether population-specific genetic risk factors are contributing to the spike in sudden deaths and racial health disparities observed in COVID-19 epicenters remains to be proven, and given the lack of banked DNA in these epicenters, the investigators question whether the speculation may even be testable.

“The genetic variant p.Ser1103Tyr-SCN5A, is a potentially proarrhythmic, sudden cardiac death marker for African Americans, and seeking its presence and respecting it is long overdue,” asserted senior author and genetic cardiologist Michael J. Ackerman, MD, PhD, Department of Cardiovascular Medicine (Division of Heart Rhythm Services), Department of Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Windland Smith Rice Cardiovascular Genomics Laboratory, Mayo Clinic, Rochester, MN, USA.

As recent studies have shown that hydroxychloroquine is not effective in the treatment of sick, hospitalized COVID-19 patients, the authors advocate against its use in that setting. Nevertheless, if COVID-19-directed, QTc-prolonging agents such as hydroxychloroquine are to be used, the investigators recommend careful cardiac monitoring, preferably in a way that spares personal protective equipment.

The authors call for research into the link between p.Ser1103Tyr-SCN5A and rates of sudden death and COVID-19-related mortality, suggesting the use of existing DNA biobanks such as the United Kingdom Biobank, a study that investigates the contribution of genetic and environmental factors to the development of disease, and the Jackson Heart Study, a large, community-based investigation into the causes of cardiovascular disease in African Americans. Point-of-care genetic testing for p.Ser1103Tyr-SCN5A should be investigated.

And finally, the authors recommend studies of medications that may better protect at-risk individuals, especially African Americans, in the context of the ongoing COVID-19 pandemic.

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Notes for editors
The article is “Genetic susceptibility for COVID-19--associated sudden cardiac death in African Americans,” by John R. Giudicessi, MD, PhD, Dan M. Roden, MD, Arthur A.M. Wilde, MD, PhD, and Michael J. Ackerman, MD, PhD (https://doi.org/10.1016/j.hrthm.2020.04.045). It appears in Heart Rhythm, published by Elsevier.

The article is openly available at www.heartrhythmjournal.com/article/S1547-5271(20)30419-7/fulltext.

Full text of this article is also available to credentialed journalists upon request; contact Jane Grochowski at +1 406 542 8397 or hmsmedia@elsevier.com. Journalists who wish to interview the authors should contact Michael J. Ackerman, MD, PhD, at ackerman.michael@mayo.edu.

Elsevier’s Novel Coronavirus Information Center provides the latest early stage and peer-reviewed research on the novel coronavirus and COVID-19. All resources are free to access and include guidelines for clinicians and patients. The Information Center links to the Coronavirus Hub on ScienceDirect, with more than 30,000 articles relevant to coronavirus, SARS, and MERS freely available. The center also links to a Healthcare Hub with resources for clinicians treating COVID-19 patients. www.elsevier.com/connect/coronavirus-information-center

About Heart Rhythm
Heart Rhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability. It integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community. www.heartrhythmjournal.com

About the Heart Rhythm Society
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal healthcare policies and standards. The Heart Rhythm Society is the preeminent professional group representing more than 5,100 specialists in cardiac pacing and electrophysiology from more than 70 countries. www.HRSonline.org

About Elsevier
Elsevier is a global information analytics business that helps scientists and clinicians to find new answers, reshape human knowledge, and tackle the most urgent human crises. For 140 years, we have partnered with the research world to curate and verify scientific knowledge. Today, we’re committed to bringing that rigor to a new generation of platforms. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, 39,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX, a global provider of information-based analytics and decision tools for professional and business customers. www.elsevier.com

Media contact
Jane Grochowski, Publisher
Elsevier
+1 406 542 8397
hmsmedia@elsevier.com