We read with interest the paper by Kumar et al. on the prevalence of bradycardia and its association with mortality in patients with coronavirus disease 2019 (COVID-19).¹ Among 1053 patients hospitalized with COVID-19, 24.9% had absolute (<60 bpm) and 13.0% profound (<50 bpm) bradycardia.¹ Subjects with absolute bradycardia exhibited a higher mortality risk compared with those with normal heart rhythm (odds ratio: 6.59; 95% confidence interval: 2.83–15.36).¹

It is well established that SARS-CoV-2 infection is associated with cardiovascular complications, such as myocardial infarction, myocarditis, and rhythm abnormalities, including bradycardia.^{2, 3} Severe hypoxia, inflammatory damage of cardiac pacemaker cells in the setting of myocarditis, myocardial ischemia, electrolyte and intravascular volume imbalances, along with cytokine release syndrome and drug-associated side effects have been proposed as probable causes of arrhythmias in this setting.³

Corticosteroids, remdesivir, tocilizumab, and anakinra are the commonly used drugs in hospitalized patients with COVID-19.^{4, 5} Among them, remdesivir has been previously associated with bradycardia.^{6, 7} Mitochondrial dysfunction prompted by the strong affinity of remdesivir for human mitochondrial RNA polymerase (h-mtRNAP), along with atrioventricular nodal inhibition due to its resemblance with adenosine, could be potential mechanisms.⁷ Kumar et al. reported that 28.7% of patients treated with remdesivir developed an absolute bradycardic response.¹ In this regard, a formal statistical comparison between patients on versus off remdesivir would be useful in determining whether this medication was associated with increased bradycardia risk in their study. Moreover, the association of day of remdesivir administration with bradycardia diagnosis should be explored. Finally, it would be quite interesting if the authors investigated any association between remdesivir-associated bradycardia and mortality.

Bradycardia is frequent and clinically relevant in patients with COVID-19. Additional studies are needed to elucidate its underlying pathophysiological mechanisms.

我们饶有兴趣地阅读了 Kumar 等人的论文。关于心动过缓的患病率及其与 2019 年冠状病毒病 (COVID-19) 患者死亡率的关系。¹在因 COVID-19 住院的 1053 名患者中，24.9% 有绝对性（<60 bpm）和 13.0% 重度（<50 bpm）心动过缓。¹与心律正常的受试者相比，绝对心动过缓受试者的死亡风险更高（优势比：6.59；95% 置信区间：2.83-15.36）。¹

众所周知，SARS-CoV-2 感染与心血管并发症有关，例如心肌梗塞、心肌炎和心律异常，包括心动过缓。^{2, 3}在心肌炎、心肌缺血、电解质和血管内容量失衡的情况下，严重缺氧、心脏起搏器细胞的炎症损伤，以及细胞因子释放综合征和药物相关的副作用已被认为是这种情况下心律失常的可能原因。³

皮质类固醇、瑞德西韦、托珠单抗和阿那白滞素是 COVID-19 住院患者的常用药物。^4、5其中，瑞德西韦此前曾与心动过缓有关。^{6, 7}瑞德西韦对人类线粒体 RNA 聚合酶 (h-mtRNAP) 的强亲和力引起的线粒体功能障碍，以及由于其与腺苷相似而导致的房室结抑制，这可能是潜在的机制。⁷库马尔等人。报告称，接受瑞德西韦治疗的患者中有 28.7% 出现了绝对心动过缓反应。¹在这方面，使用瑞德西韦与不使用瑞德西韦的患者之间进行正式的统计比较将有助于确定该药物是否与他们研究中的心动过缓风险增加有关。此外，应探讨瑞德西韦给药天数与心动过缓诊断之间的关联。最后，如果作者调查瑞德西韦相关的心动过缓与死亡率之间的任何关联，那将是非常有趣的。

心动过缓在 COVID-19 患者中很常见且具有临床意义。需要更多的研究来阐明其潜在的病理生理机制。