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Review
. 2023 Sep 1:10:1256512.
doi: 10.3389/fcvm.2023.1256512. eCollection 2023.

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers

Karina Carvalho Marques  1 , Juarez Antônio Simões Quaresma #  1   2   3 , Luiz Fábio Magno Falcão #  1   2
Affiliations
Review

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers

Karina Carvalho Marques et al. Front Cardiovasc Med. .

Abstract

Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID.

Keywords: Long COVID; autonomic diseases; autonomic nervous system; heart rate variability; inflammation; pathophysiology.

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Conflict of interest statement

JASQ is a member of the editorial board of Frontiers in Cardiovascular Medicine. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Autonomic Pathophysiology of Long COVID (Created with BioRender.com). SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE2, angiotensin-converting enzyme 2; S12, SARS-CoV-2 spike protein; α7 nAChRs, α7 nicotinic acetylcholine receptors; CNS, central nervous system; PNS, peripheral nervous system; PSNS, parasympathetic nervous system; SNS, sympathetic nervous system; CD4+, T lymphocyte CD4+; CD8+, T lymphocyte CD8+; type III interferon (IFN-β, -γ1), T lymphocyte types: CD38, CD86, CD14α, CD16α; IL-9, interleukin 9; IL-6, interleukin 6; ANS, autonomic nervous system.
Figure 2
Figure 2
Association of heart rate variability and inflammatory markers (created with BioRender.com). HRV, heart rate variability; LDH, lactate dehydrogenase; ANS, autonomic nervous system; PNS, peripheral nervous system; PSNS, parasympathetic nervous system; SNS, sympathetic nervous system; HF-HRV, high-frequency HRV; LF-HRV, low-frequency HRV.
Figure 3
Figure 3
Autonomic nervous system and heart rate variability in Long COVID (created with BioRender.com). SNS, sympathetic nervous system; PSNS, parasympathetic nervous system; HRV, heart rate variability; HR, heart rate.
See this image and copyright information in PMC

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