Attenuated cardiac autonomic function in patients with long-COVID with impaired orthostatic hemodynamics

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.