Thank you Dr. Imamura and Colleagues. We appreciate your input and thoughts on further studying bradycardia and COVID-19. Our large-scale multicenter retrospective study included over 1000 patients with COVID-19, and found that absolute bradycardia was noted in 24.9% of the study cohort and these individuals were found to have a significant increase in mortality.

We agree with you that differentiating the type of bradycardia in a patient is important to determine the etiology, and ultimately, the appropriate treatment. However, the data included in our study was obtained from March, 2020 to August, 2020 during the early phase of the pandemic when staff exposure to COVID patients was limited. As a result, echocardiogram and 12-lead EKG's were typically completed only once during admission, if indicated. As this was a retrospective study, we had to examine whatever data and tests had been collected. We believe that in the future a prospective study evaluating the etiology of bradycardia with these tests is important to obtain thorough diagnosis and treatment.¹

Given the high prevalence of absolute bradycardia in our study population, clinicians should carefully consider next steps in treating absolute bradycardia in the inpatient setting. The European Society of Cardiology suggested an initial trial of isoprenaline and atropine, and if bradycardia is sustained, temporary pacing should be considered.² However, a recent Italian paper proposed an early permanent pacemaker implantation to avoid the increased risk of infection that exists when a temporary pacemaker is placed.³ Brignole et al reported that a temporary pacemaker before a permanent pacemaker implantation is 2.5 times more likely to develop a risk of infection versus the latter.⁴ Chintz et al had seven patients with COVID-19 that developed bradyarrhythmias in which they placed three temporary and four leadless pacemakers. Despite placing the pacemakers, they noted a short term morbidity and subsequent death due to COVID-19 complications in five out of seven patients.⁵ Based on the current literature available and the novel analysis in our study, it is important that that the international community research the next steps to address bradycardia and COVID-19.

A future study, specifically a retrospective cohort separating pre-existing heart failure from those without pre-existing heart failure may help to differentiate respiratory failure versus heart failure as the cause of mortality. As for myocarditis in COVID-19; The CDC has recently reported that myocarditis post mRNA COVID-19 vaccination is a well-known complication.

We look forward to any further input and suggestions that Dr. Imamura and Colleagues may have.

谢谢今村博士和同事们。我们感谢您对进一步研究心动过缓和 COVID-19 的意见和想法。我们的大规模多中心回顾性研究纳入了 1000 多名 COVID-19 患者，发现在 24.9% 的研究队列中注意到绝对心动过缓，并且发现这些人的死亡率显着增加。

我们同意您的观点，区分患者心动过缓的类型对于确定病因以及最终确定适当的治疗很重要。但是，我们研究中包含的数据是从 2020 年 3 月至 2020 年 8 月在大流行的早期阶段获得的，当时员工接触 COVID 患者的机会有限。因此，如果有指示，超声心动图和 12 导联心电图通常仅在入院期间完成一次。由于这是一项回顾性研究，我们必须检查收集到的所有数据和测试。我们相信，未来通过这些测试评估心动过缓病因的前瞻性研究对于获得彻底的诊断和治疗非常重要。¹

鉴于我们研究人群中绝对心动过缓的高患病率，临床医生应仔细考虑在住院环境中治疗绝对心动过缓的后续步骤。欧洲心脏病学会建议对异丙肾上腺素和阿托品进行初步试验，如果心动过缓持续，应考虑临时起搏。²然而，最近的一篇意大利论文提议尽早植入永久性起搏器，以避免在放置临时起搏器时增加感染风险。³ Brignole 等人报告说，在植入永久性起搏器之前使用临时起搏器发生感染风险的可能性是后者的 2.5 倍。⁴Chintz 等人有 7 名 COVID-19 患者出现缓慢性心律失常，他们在其中放置了三个临时起搏器和四个无引线起搏器。尽管放置了起搏器，但他们注意到七分之五的患者因 COVID-19 并发症而出现短期发病率和随后的死亡。⁵根据现有文献和我们研究中的新颖分析，重要的是国际社会研究解决心动过缓和 COVID-19 的后续步骤。

未来的一项研究，特别是一项回顾性队列，将预先存在的心力衰竭与没有预先存在的心力衰竭的患者分开，可能有助于区分呼吸衰竭与心力衰竭作为死亡原因。至于 COVID-19 中的心肌炎；CDC 最近报告说，mRNA COVID-19 疫苗接种后的心肌炎是一种众所周知的并发症。

我们期待着今村博士和同事们的任何进一步意见和建议。