Increased interleukin-6 levels are associated with atrioventricular conduction delay in severe COVID-19 patients

Riccardo Accioli; Pietro Enea Lazzerini; Viola Salvini; Alessandra Cartocci; Decoroso Verrengia; Tommaso Marzotti; Fabio Salvadori; Stefania Bisogno; Gabriele Cevenini; Michele Voglino; Severino Gallo; Sabrina Pacini; Martina Pazzaglia; Angelica Tansini; Ambra Otranto; Franco Laghi-Pasini; Maurizio Acampa; Mohamed Boutjdir; Pier Leopoldo Capecchi

doi:10.1002/joa3.13114

Increased interleukin-6 levels are associated with atrioventricular conduction delay in severe COVID-19 patients

J Arrhythm. 2024 Jul 31;40(5):1137-1148. doi: 10.1002/joa3.13114. eCollection 2024 Oct.

Authors

Riccardo Accioli^{1

2}, Pietro Enea Lazzerini^{1

2}, Viola Salvini^{1

2}, Alessandra Cartocci³, Decoroso Verrengia^{1

2}, Tommaso Marzotti^{1

2}, Fabio Salvadori^{1

2}, Stefania Bisogno^{1

2}, Gabriele Cevenini³, Michele Voglino^{1

2}, Severino Gallo^{1

2}, Sabrina Pacini^{1

2}, Martina Pazzaglia^{1

2}, Angelica Tansini^{1

2}, Ambra Otranto^{1

2}, Franco Laghi-Pasini^{1

2}, Maurizio Acampa⁴, Mohamed Boutjdir^{5

6}, Pier Leopoldo Capecchi^{1

2}

Affiliations

¹ Department of Medical Sciences, Surgery and Neurosciences University of Siena Siena Italy.
² Division of Internal Medicine and Geriatrics, Electroimmununology Unit University Hospital of Siena Siena Italy.
³ Department of Medical Biotechnologies University of Siena Siena Italy.
⁴ Stroke Unit University Hospital of Siena Siena Italy.
⁵ VA New York Harbor Healthcare System SUNY Downstate Health Sciences University New York New York USA.
⁶ NYU Grossman School of Medicine New York New York USA.

Abstract

Background: Severely ill patients with coronavirus disease 2019 (COVID-19) show an increased risk of new-onset atrioventricular blocks (AVBs), associated with high rates of short-term mortality. Recent data suggest that the uncontrolled inflammatory activation observed in these patients, specifically interleukin (IL)-6 elevation, may play an important pathogenic role by directly affecting cardiac electrophysiology. The aim of our study was to assess the acute impact of IL-6 changes on electrocardiographic indices of atrioventricular conduction in severe COVID-19.

Methods: We investigated (1) the behavior of PR-interval and PR-segment in patients with severe COVID-19 during active phase and recovery, and (2) their association with circulating IL-6 levels over time.

Results: During active disease, COVID-19 patients showed a significant increase of PR-interval and PR-segment. Such atrioventricular delay was transient as these parameters rapidly normalized during recovery. PR-indices significantly correlated with circulating IL-6 levels over time. All these changes and correlations persisted also in the absence of laboratory signs of cardiac strain/injury or concomitant treatment with PR-prolonging drugs, repurposed or not.

Conclusions: Our study provides evidence that in patients with severe COVID-19 and high-grade systemic inflammation, IL-6 elevation is associated with a significant delay of atrioventricular conduction, independent of concomitant confounding factors. While transient, such alterations may enhance the risk of severe AVB and associated short-term mortality. Our data provide further support to current anti-inflammatory strategies for severe COVID-19, including IL-6 antagonists.

Keywords: COVID‐19; PR‐interval; PR‐segment; atrioventricular block; interleukin‐6.