Department of Internal Medicine, San Francesco Hospital, Viale Europa 21, 82037 Telese Terme, Italy.
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, 80131 Naples, Italy.
Viruses. 2022 May 13;14(5):1035. doi: 10.3390/v14051035.
Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.
慢性 COVID-19 是指在“急性 COVID-19”阶段之后持续或出现的症状和体征。这些患者存在多器官功能障碍、再入院和死亡的风险增加。在慢性 COVID-19 患者中，可以检测到 D-二聚体、NT-ProBNP 和自主神经系统功能持续增加。为了验证慢性 COVID-19 患者自主神经功能紊乱的假说，我们使用 12 导联 24 小时心电图监测对 30 名慢性 COVID-19 患者和 20 名非 COVID 患者进行了心率变异性研究。慢性 COVID-19 患者的心率变异性总功率（7.46 ± 0.5 对 8.08 ± 0.6；p < 0.0001；Cohen's d = 1.12）和 VLF（6.84 ± 0.8 对 7.66 ± 0.6；p < 0.0001；Cohen's d = 1.16）和 HF（4.65 ± 0.9 对 5.33 ± 0.9；p = 0.015；Cohen's d = 0.76）成分均较低。慢性 COVID-19 患者的 LF/HF 比值明显较高（1.46 ± 0.27 对 1.23 ± 0.13；p = 0.001；Cohen's d = 1.09）。多变量分析表明，慢性 COVID-19 与 D-二聚体（标准化β系数= 0.259）、NT-ProBNP（标准化β系数= 0.281）、频谱分析的 HF 成分（标准化β系数= 0.696）和 LF/HF 比值（标准化β系数= 0.820）显著相关。自主神经功能紊乱可能解释了慢性 COVID-19 患者持续存在的症状。促凝状态的持续存在和心肌应变的升高可能解释了这些患者的迷走神经损伤。在慢性 COVID-19 患者中，迷走神经活动受损、NT-ProBNP 持续升高和血栓前状态需要仔细监测和适当干预。
