Hira Rashmin, Baker Jacquie R, Siddiqui Tanya, Patel Aishani, Valani Felix Gabriel Ayala, Lloyd Matthew G, Floras John S, Morillo Carlos A, Sheldon Robert S, Raj Satish R
Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, GAC70 HRIC Building, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
Department of Medicine, University Health Network and Sinai Health, University of Toronto, Toronto, ON, Canada.
Clin Auton Res. 2025 Apr;35(2):301-314. doi: 10.1007/s10286-025-01107-x. Epub 2025 Jan 22.
Long-coronavirus disease (long-COVID) is associated with initial orthostatic hypotension and postural orthostatic tachycardia syndrome. Whether altered autonomic tone underlies these abnormalities is unknown. We compared autonomic function between patients with long-COVID and healthy controls, and within patients with long-COVID with different orthostatic hemodynamic phenotypes.
Patients with long-COVID (n = 94; F = 76; 42 years [36, 53 years] with initial orthostatic hypotension: n = 40; F = 32; 49 years [39, 57 years]; postural orthostatic tachycardia syndrome: n = 29; F = 26; 39 years [33, 47 years]; or no abnormalities: n = 25; F = 18; 42 years [35, 49 years]), and healthy controls (n = 33; F = 25; 49 years [30, 62 years]) completed a 10-min active stand with beat-to-beat hemodynamics. Heart rate variability, blood pressure variability, and baroreflex sensitivity were calculated as indirect measures of cardiovascular autonomic health. Continuous data (median [95% confidence interval]) were analyzed with Mann-Whitney U tests or Kruskal-Wallis tests with Dunn's corrections.
Patients with long-COVID had lower upright high frequency heart rate variability (p = 0.04) and low frequency blood pressure variability (p = 0.001) than controls. Patients with initial orthostatic hypotension had lower supine baroreflex sensitivity compared with patients without abnormalities (p = 0.01), and lower supine baroreflex sensitivity (p = 0.001) and high frequency heart rate variability (p = 0.03) than patients with postural orthostatic tachycardia syndrome. Patients with postural orthostatic tachycardia syndrome had lower upright high frequency heart rate variability (p < 0.001) and baroreflex sensitivity (p < 0.001) compared with patients without abnormalities and lower upright low frequency blood pressure variability (p = 0.04) compared with controls.
Patients with long-COVID have attenuated cardiac autonomic function. Patients with initial orthostatic hypotension have lower supine baroreflex sensitivity. Patients with postural orthostatic tachycardia syndrome have lower upright vascular sympathetic and cardiac parasympathetic modulation. Long-COVID subgroups do not present with homogeneous pathophysiology, necessitating targeted treatment strategies.
长期新冠病毒病（长新冠）与初始直立性低血压和体位性直立性心动过速综合征有关。自主神经张力改变是否是这些异常的基础尚不清楚。我们比较了长新冠患者与健康对照者之间的自主神经功能，以及长新冠患者中不同直立性血流动力学表型者的自主神经功能。
长新冠患者（n = 94；女性 = 76；年龄42岁[36, 53岁]，初始直立性低血压者：n = 40；女性 = 32；年龄49岁[39, 57岁]；体位性直立性心动过速综合征者：n = 29；女性 = 26；年龄39岁[33, 47岁]；或无异常者：n = 25；女性 = 18；年龄42岁[35, 49岁]），以及健康对照者（n = 33；女性 = 25；年龄49岁[30, 62岁]）完成了10分钟的主动站立并同步测量血流动力学。计算心率变异性、血压变异性和压力反射敏感性作为心血管自主神经健康的间接指标。连续数据（中位数[95%置信区间]）采用Mann-Whitney U检验或经Dunn校正的Kruskal-Wallis检验进行分析。
长新冠患者的直立高频心率变异性（p = 0.04）和低频血压变异性（p = 0.001）低于对照组。初始直立性低血压患者与无异常患者相比，仰卧位压力反射敏感性较低（p = 0.01），与体位性直立性心动过速综合征患者相比，仰卧位压力反射敏感性较低（p = 0.001）且高频心率变异性较低（p = 0.03）。与无异常患者相比，体位性直立性心动过速综合征患者的直立高频心率变异性较低（p < 0.001）和压力反射敏感性较低（p < 0.001），与对照组相比，直立低频血压变异性较低（p = 0.04）。
长新冠患者的心脏自主神经功能减弱。初始直立性低血压患者的仰卧位压力反射敏感性较低。体位性直立性心动过速综合征患者的直立血管交感神经和心脏副交感神经调制较低。长新冠亚组不存在同质的病理生理学，需要有针对性的治疗策略。
