Liviero Filippo, Scapellato Maria Luisa, Volpin Anna, Battistella Monica, Fabris Laura, Brischigliaro Laura, Folino Franco, Moretto Angelo, Mason Paola, Pavanello Sofia
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy.
Occupational Medicine Unit, University Hospital of Padova, Padova, Italy.
Front Neurol. 2024 May 17;15:1403551. doi: 10.3389/fneur.2024.1403551. eCollection 2024.
Prior investigations into post-COVID dysautonomia often lacked control groups or compared affected individuals solely to healthy volunteers. In addition, no data on the follow-up of patients with SARS-CoV-2-related autonomic imbalance are available.
In this study, we conducted a comprehensive clinical and functional follow-up on healthcare workers (HCWs) with former mild COVID-19 (group 1, n = 67), to delineate the trajectory of post-acute autonomic imbalance, we previously detected in a case-control study. Additionally, we assessed HCWs for which a test before SARS-CoV-2 infection was available (group 2, n = 29), who later contracted SARS-CoV-2, aiming to validate findings from our prior case-control investigation. We evaluated autonomic nervous system heart modulation by means of time and frequency domain heart rate variability analysis (HRV) in HCWs during health surveillance visits. Short-term electrocardiogram (ECG) recordings, were obtained at about 6, 13 months and both at 6 and 13 months from the negative SARS-CoV-2 naso-pharyngeal swab (NPS) for group 1 and at about 1-month from the negative NPS for group 2. HCWs who used drugs, had comorbidities that affected HRV, or were hospitalized with severe COVID-19 were excluded.
Group 1 was split into three subgroups clinically and functionally followed at, about 6 months (subgroup-A, = 17), 13 months (subgroup-B, = 37) and both at 6 and 13 months (subgroup-C, = 13) from the negative SARS-CoV-2 NPS. In subgroup-A, at 6-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed an increase in normalized high frequency power (nHF) ( = 2.99, = 0.009), a decrease in the normalized low frequency power (nLF) ( = 2.98, = 0.009) and in the LF/HF ratio ( = 3.13, p = 0.006). In subgroup B, the comparison of the spectral components in the frequency domain HRV parameters, at 13-month follow-up compared with baseline, showed an increase in nHF ( = 2.54, = 0.02); a decrease in nLF ( = 2.62, = 0.01) and in the LF/HF ratio ( = 4.00, = 0.0003). In subgroup-C, at both 6 and 13-month follow-ups, the spectral components in the frequency domain HRV parameters were higher than baseline in nHF ( = 2.64, p = 0.02 and ( = 2.13, = 0.05, respectively); lower in nLF ( = 2.64, p = 0.02 and ( = 2.13, p = 0.05, respectively), and in LF/HF ( = 1.92, p = 0.08 and ( = 2.43, = 0.03, respectively). A significant proportion of HCWs reported persistent COVID-19 symptoms at both the 6 and 13-month follow-ups, seemingly unrelated to cardiac autonomic balance. In group 2 HCWs, at 1-month follow-up compared with baseline, the spectral components in the frequency domain HRV parameters, showed a decrease in nHF ( = 2.19, = 0.04); an increase in nLF ( = 2.15, = 0.04) and in LF/HF ( = 3.49, = 0.002).
These results are consistent with epidemiological data suggesting a higher risk of acute cardiovascular complications during the first 30 days after COVID-19. The SARS-CoV-2 associated autonomic imbalance in the post-acute phase after recovery of mild COVID-19 resolved 6 months after the first negative SARS-CoV-2 NPS. However, a significant proportion of HCWs reported long-term COVID-19 symptoms, which dot not seems to be related to cardiac autonomic balance. Future research should certainly further test whether autonomic imbalance has a role in the mechanisms of long-COVID syndrome.
先前对新冠后自主神经功能障碍的研究往往缺乏对照组,或者仅将受影响个体与健康志愿者进行比较。此外,目前尚无关于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)相关自主神经失衡患者随访的数据。
在本研究中,我们对曾患轻度新冠的医护人员(第1组,n = 67)进行了全面的临床和功能随访,以描绘我们先前在一项病例对照研究中检测到的急性后自主神经失衡的轨迹。此外,我们评估了在感染SARS-CoV-2之前进行过检测的医护人员(第2组,n = 29),这些人后来感染了SARS-CoV-2,旨在验证我们先前病例对照研究的结果。在健康监测访视期间,我们通过时域和频域心率变异性分析(HRV)评估医护人员的自主神经系统心脏调节。第1组在SARS-CoV-2鼻咽拭子(NPS)阴性后约6个月、13个月以及6个月和13个月时获取短期心电图(ECG)记录,第2组在NPS阴性后约1个月时获取记录。排除使用药物、患有影响HRV的合并症或因重症新冠住院的医护人员。
第1组在临床上和功能上分为三个亚组,分别在SARS-CoV-2 NPS阴性后约6个月(A亚组, = 17)、13个月(B亚组, = 37)以及6个月和13个月(C亚组, = 13)进行随访。在A亚组中,与基线相比,在6个月随访时,频域HRV参数的频谱成分显示归一化高频功率(nHF)增加( = 2.99, = 0.009),归一化低频功率(nLF)降低( = 2.98, = 0.009),低频/高频比值降低( = 3.13,p = 0.006)。在B亚组中,与基线相比,在13个月随访时,频域HRV参数的频谱成分显示nHF增加( = 2.54, = 0.02);nLF降低( = 2.62, = 0.01),低频/高频比值降低( = 4.00, = 0.0003)。在C亚组中,在6个月和13个月随访时,频域HRV参数的频谱成分在nHF方面均高于基线(分别为 = 2.64,p = 0.02和( = 2.13, = 0.05);在nLF方面较低(分别为 = 2.64,p = 0.02和( = 2.13,p = 0.05),在低频/高频比值方面(分别为 = 1.92,p = 0.08和( = 2.43, = 0.03)。相当一部分医护人员在6个月和13个月随访时均报告有持续的新冠症状,这似乎与心脏自主神经平衡无关。在第2组医护人员中,与基线相比,在1个月随访时,频域HRV参数的频谱成分显示nHF降低( = 2.19, = 0.04);nLF增加( = 2.15, = 0.04),低频/高频比值增加( = 3.49, = 0.002)。
这些结果与流行病学数据一致,表明在新冠后30天内急性心血管并发症风险较高。轻度新冠康复后急性期的SARS-CoV-2相关自主神经失衡在首次SARS-CoV-2 NPS阴性后6个月得到缓解。然而,相当一部分医护人员报告有长期新冠症状,这似乎与心脏自主神经平衡无关。未来的研究肯定应该进一步测试自主神经失衡是否在长期新冠综合征的机制中起作用。