Linear and non‑linear indices of vagal nerve in relation to sex and inflammation in patients with Covid‑19

Hunakova,Luba; Sabaka,Peter; Zvarik,Milan; Mikolaskova,Iveta; Gidron,Yori; Bucova,Maria

doi:10.3892/br.2023.1662

Linear and non‑linear indices of vagal nerve in relation to sex and inflammation in patients with Covid‑19

Authors:
- Luba Hunakova
- Peter Sabaka
- Milan Zvarik
- Iveta Mikolaskova
- Yori Gidron
- Maria Bucova
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Affiliations: Institute of Immunology, Faculty of Medicine, Comenius University, 813 72 Bratislava, Slovakia, Department of Infectology and Geographical Medicine, Faculty of Medicine, Comenius University, 833 05 Bratislava, Slovakia, Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Computer Science, Comenius University, 84248 Bratislava, Slovakia, Department of Nursing, Faculty of Welfare and Health Sciences, University of Haifa, Haifa 3498838, Israel
Published online on: September 20, 2023 https://doi.org/10.3892/br.2023.1662
Article Number: 80
Copyright: © Hunakova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperinflammation is one of the most important pathophysiological risk factors for poor prognosis in patients with coronavirus disease‑2019 (Covid‑19). Low vagal neuro‑immune modulation can lead into this kind of immune dysregulation. The association between vagal activity, sex and inflammatory markers were investigated in patients with Covid‑19. A total of 19 patients with Covid‑19 were included in the present study. Vagus nerve activity was indexed by heart rate variability (HRV) derived from electrocardiogram at hospital admission. Linear HRV parameters included the root mean square of successive RR interval differences (RMSSD) and high‑frequency HRV (HF‑HRV), while non‑linear parameters included 2 UV%. Immune/inflammatory parameters included C‑reactive protein (CRP), interleukin‑6 (IL‑6), neutrophil/lymphocyte ratio (NLR), systemic inflammatory index (SII), and procalcitonin (PCT). It has been revealed that both linear HRV indices HF‑HRV and RMSSD, are significantly negatively correlated with CRP and IL‑6, independent of age. The non‑linear index of 2 UV% is significantly negatively correlated with NLR and SII, which reflect subtle changes in the response of immunocompetent cells. Patients that received high‑flow nasal oxygen therapy had significantly higher IL‑6 and CRP levels and lower levels of HF‑HRV and RMSSD. These patients also had a significantly longer length of stay in hospital (LOS) than patients receiving low‑flow oxygen therapy. Men had higher plasma PCT levels and longer LOS in hospital than women, and PCT statistically explained (mediated) the association between sex and LOS. The present study showed different correlations of linear and non‑linear vagal indexes of HRV and inflammatory markers in patients with Covid‑19. Significant sex differences in certain inflammatory markers were also observed, which may very well verify previous findings of poor prognosis in men with Covid‑19. HRV reflects a continuous interaction between the sympathetic and parasympathetic autonomic nervous systems, which are affected by mental or physical stress, and certain disease states. The increased sympathetic and decreased parasympathetic vagal tone contribute to a higher risk of diseases associated with inflammation, cardiovascular disease, cancer, pulmonary diseases and other pathologies, including infectious diseases such as Covid‑19. The present study showed that higher RMSSD (a marker of vagal activity) in Covid‑19 patients is associated with lower levels of inflammatory biomarkers, a lower need for treatment and is negatively correlated with intensive care unit admission, leading to a shorter hospital stay. These findings support the idea that activation of vagus nerve may help certain Covid‑19 patients by reducing the cytokine storm and excessive inflammation.

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