Hunakova Luba, Sabaka Peter, Zvarik Milan, Mikolaskova Iveta, Gidron Yori, Bucova Maria
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.
Biomed Rep. 2023 Sep 20;19(5):80. doi: 10.3892/br.2023.1662. eCollection 2023 Nov.
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.
炎症风暴是2019冠状病毒病（Covid-19）患者预后不良的最重要病理生理风险因素之一。迷走神经免疫调节功能低下可导致这种免疫失调。本研究调查了Covid-19患者迷走神经活动、性别与炎症标志物之间的关联。本研究共纳入19例Covid-19患者。入院时通过心电图得出的心率变异性（HRV）来衡量迷走神经活动。线性HRV参数包括连续RR间期差值的均方根（RMSSD）和高频HRV（HF-HRV），而非线性参数包括2 UV%。免疫/炎症参数包括C反应蛋白（CRP）、白细胞介素-6（IL-6）、中性粒细胞/淋巴细胞比值（NLR）、全身炎症指数（SII）和降钙素原（PCT）。研究发现，线性HRV指标HF-HRV和RMSSD均与CRP和IL-6显著负相关，且不受年龄影响。2 UV%的非线性指标与反映免疫活性细胞反应细微变化的NLR和SII显著负相关。接受高流量鼻导管吸氧治疗的患者IL-6和CRP水平显著更高，但HF-HRV和RMSSD水平更低。与接受低流量吸氧治疗的患者相比，这些患者的住院时间（LOS）也显著更长。男性的血浆PCT水平更高，住院时间也比女性更长，且PCT在统计学上解释（介导）了性别与住院时间之间的关联。本研究显示，Covid-19患者HRV的线性和非线性迷走神经指标与炎症标志物存在不同的相关性。还观察到某些炎症标志物存在显著的性别差异，这很可能证实了先前关于Covid-19男性患者预后不良的研究结果。HRV反映了交感神经和副交感神经自主神经系统之间的持续相互作用，它们会受到精神或身体压力以及某些疾病状态的影响。交感神经活动增强和副交感神经迷走神经张力降低会增加与炎症、心血管疾病、癌症、肺部疾病和其他病理状况相关的疾病风险，包括如Covid-19等传染病。本研究表明，Covid-19患者中较高的RMSSD（迷走神经活动的一个指标）与较低水平的炎症生物标志物、较低的治疗需求相关，且与入住重症监护病房呈负相关，从而导致住院时间缩短。这些发现支持了激活迷走神经可能通过减少细胞因子风暴和过度炎症来帮助某些Covid-19患者的观点。
