Investigating autonomic nervous system dysfunction among patients with post-COVID condition and prolonged cardiovascular symptoms

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19), which threatens human health and public safety. In this Review, we describe the basic virology of SARS-CoV-2, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses. We summarize current knowledge of clinical, epidemiological and pathological features of COVID-19, as well as recent progress in animal models and antiviral treatment approaches for SARS-CoV-2 infection. We also discuss the potential wildlife hosts and zoonotic origin of this emerging virus in detail.

The powers of the low-frequency (LF) and high-frequency (HF) oscillations characterizing heart rate variability (HRV) appear to reflect, in their reciprocal relationship, changes in the state of the sympathovagal balance occurring during numerous physiological and pathophysiological conditions. However, no adequate information is available on the quantitative resolution of this methodology. We studied 22 healthy volunteers (median age, 46.5 years) who were subjected after a rest period to a series of passive head-up tilt steps randomly chosen from the following angles: 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 90 degrees. From the continuous ECG, after appropriate analog-to-digital conversion, a personal computer was used to compute, with an autoregressive methodology, time and frequency domain indexes of RR interval variability. Spectral and cross-spectral analysis with the simultaneously recorded respiratory signal excluded its contribution to LF. Age was significantly correlated to variance and to the absolute values in milliseconds squared of very-low-frequency (VLF), LF, and HF components. The tilt angle was correlated to both LF and HF (expressed in normalized units [nu]) and to the LF-to-HF ratio (r = .78, -.72, and .68; respectively). Lower levels of correlation were found with HF (in ms2) and RR interval. No correlation was present between tilt angle and variance, VLF, or LF (in ms2). Individual analysis confirmed that the use of nu provided the greatest consistency of results. Spectral analysis of HRV, using nu or LF-to-HF ratio, appears to be capable of providing a noninvasive quantitative evaluation of graded changes in the state of the sympathovagal balance.

In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at approximately 0.25 Hz and a low frequency at approximately 0.1 Hz, with a normalized low frequency:high frequency ratio of 3.6 +/- 0.7. With tilt, the low-frequency component became largely predominant (90 +/- 1%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency:high frequency ratio induced by tilt. Chronic beta-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency:high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency:high frequency ratio (0.7 +/- 0.1); during tilt, the increase in the low frequency:high frequency ratio (8.3 +/- 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency:high frequency ratio at rest of 2.8 +/- 0.7, which became 17 +/- 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation.(ABSTRACT TRUNCATED AT 400 WORDS)