Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

Milovanovic, Branislav; Djajic, Vlado; Bajić, Dragana; Djoković, Aleksandra; Krajnovic, Tatjana; Jovanovic, Sladjana; Verhaz, Antonija; Kovačević, Peđja; Ostojić, Miodrag

doi:10.3389/fnins.2021.640835

Cited by 34 publications

(92 citation statements)

References 62 publications

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“…The interpretation of V2 related to the parasympathetic activity seems quite probable if one recalls that the parasympathetic branch has the potential to introduce fast (beat to beat) changes in the heart rate, which may even lead to an asystole. The effect of autonomic dysfunction in the early stage of COVID-19 was observed previously in patients with different intensities of symptoms 31 as well as in critical conditions 9 . In the Maartje et al study, the authors discussed the separate roles of the sympathetic branch and vagus nerve in the infection 12 .…”

Section: Discussionsupporting

confidence: 54%

Heart rate variability comparison between young males after 4–6 weeks from the end of SARS-CoV-2 infection and controls

Soliński

Pawlak

Petelczyc

et al. 2022

Sci Rep

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Due to the prolonged inflammatory process induced by infection of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indices of autonomic nervous system dysfunction may persist long after viral shedding. Previous studies showed significant changes in HRV parameters in severe (including fatal) infection of SARS-CoV-2. However, few studies have comprehensively examined HRV in individuals who previously presented as asymptomatic or mildly symptomatic cases of COVID-19. In this study, we examined HRV in asymptomatic or mildly symptomatic individuals 5–7 weeks following positive confirmation of SARS-CoV-2 infection. Sixty-five ECG Holter recordings from young (mean age 22.6 ± 3.4 years), physically fit male subjects 4–6 weeks after the second negative test (considered to be the start of recovery) and twenty-six control male subjects (mean age 23.2 ± 2.9 years) were considered in the study. Night-time RR time series were extracted from ECG signals. Selected linear as well as nonlinear HRV parameters were calculated. We found significant differences in Porta’s symbolic analysis parameters V0 and V2 (p < 0.001), α2 (p < 0.001), very low-frequency component (VLF; p = 0.022) and respiratory peak (from the PRSA method; p = 0.012). These differences may be caused by the changes of activity of the parasympathetic autonomic nervous system as well as by the coupling of respiratory rhythm with heart rate due to an increase in pulmonary arterial vascular resistance. The results suggest that the differences with the control group in the HRV parameters, that reflect the functional state of the autonomic nervous system, are measurable after a few weeks from the beginning of the recovery even in the post-COVID group—a young and physically active population. We indicate HRV sensitive markers which may be used in long-term monitoring of patients after recovery.

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Section: Discussionsupporting

confidence: 54%

Heart rate variability comparison between young males after 4–6 weeks from the end of SARS-CoV-2 infection and controls

Soliński

Pawlak

Petelczyc

et al. 2022

Sci Rep

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“…Recent studies reported baroreflex dysfunction in the early phase of infection with SARS-CoV-2. 32 Our findings suggest that baroreflex dysfunction could be restored after COVID-19, since BRS was improved during follow-up. Furthermore, BRS and aPWV were inversely correlated in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 52%

Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term

Zanoli

Gaudio

Mikhailidis

et al. 2022

Circulation Research

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Background: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). Methods: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. Results: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25–48) weeks after COVID-19 onset, and they had higher carotid Young’s elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P =0.04). Moreover, aPWV (path coefficient: −0.186; P =0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (−9%; P =0.01), incremental Young’s elastic modulus (−17%; P =0.03), baroreflex sensitivity (+28%; P =0.049), heart rate variability triangular index (+15%; P =0.01), and subendocardial viability ratio (+12%; P =0.01×10 −4 ) were significantly improved. There was a trend toward improvement in brachial PWV (−6%; P =0.14) and carotid distensibility (+18%; P =0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P =0.04) remained significantly higher in patients with COVID-19 than in control subjects. Conclusions: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

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“…Noradrenergic neurons in the LC have been associated with a wide array of physiological functions including cardiovascular and respiratory control (de Carvalho et al, 2017; Oyamada et al, 1998) via direct projections to the spinal cord or projections to autonomic nuclei like the dorsal motor nucleus (DMV) of the vagus, the rostroventrolateral medulla (RVM), the Edinger-Westphal nucleus, the caudal raphe, the paraventricular nucleus, and the amygdala (Samuels and Szabadi, 2008). As autonomic functions are impaired in COVID-19 patients after infection (Becker, 2021; Milovanovic et al, 2021) and the LC is one of the regions that is associated with these functions, we tested ACE2 immunoreactivity in LC neurons after CIE exposure. Many TH-positive neurons in the LC were positive for ACE2 expression as previously reported (Hernández et al, 2021) and the number of TH-ACE2 neurons was increased in CIE mice, suggesting an increased vulnerability of LC neurons to SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Repeated ethanol exposure and withdrawal alters ACE2 expression in discrete brain regions: Implications for SARS-CoV-2 infection

Balasubramanian

James

Pushpavathi

et al. 2022

Preprint

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Emerging evidence suggests that people with alcohol use disorders are at higher risk for SARS-CoV-2. SARS-CoV-2 engages angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors for cellular entry. While ACE2 and TMPRSS2 genes are upregulated in the cortex of alcohol-dependent individuals, information on expression in specific brain regions and neural populations implicated in SARS-CoV-2 neuroinvasion, particularly monoaminergic neurons, is limited. We sought to clarify how chronic alcohol exposure affects ACE2 and TMPRSS2 expression in monoaminergic brainstem circuits and other putative SARS-CoV-2 entry points. C57BL/6J mice were exposed to chronic intermittent ethanol (CIE) vapor for 4 weeks and brains were examined using immunofluorescence. We observed increased ACE2 levels in the olfactory bulb and hypothalamus following CIE, which are known to mediate SARS-CoV-2 neuroinvasion. Total ACE2 immunoreactivity was also elevated in the raphe magnus (RMG), raphe obscurus (ROB), and locus coeruleus (LC), while in the dorsal raphe nucleus (DRN), ROB, and LC we observed increased colocalization of ACE2 with monoaminergic neurons. ACE2 also increased in the periaqueductal gray (PAG) and decreased in the amygdala. Whereas ACE2 was detected in most brain regions, TMPRSS2 was only detected in the olfactory bulb and DRN but was not significantly altered after CIE. Our results suggest that previous alcohol exposure may increase the risk of SARS-CoV-2 neuroinvasion and render brain circuits involved in cardiovascular and respiratory function as well as emotional processing more vulnerable to infection, making adverse outcomes more likely. Additional studies are needed to define a direct link between alcohol use and COVID-19 infection.

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Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

Cited by 34 publications

References 62 publications

Heart rate variability comparison between young males after 4–6 weeks from the end of SARS-CoV-2 infection and controls

Heart rate variability comparison between young males after 4–6 weeks from the end of SARS-CoV-2 infection and controls

Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term

Repeated ethanol exposure and withdrawal alters ACE2 expression in discrete brain regions: Implications for SARS-CoV-2 infection

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