## 4 Discussion  
In the present study, our data showed that the prevalence of abnormal SpO2 was 34.8% in the MHD population, and approximately 10.9% of the study patients had an ESS score of more than 10 (Table 1). As expected, the CV mortality rate (65.2%) was much higher than non-CV deaths (34.8%) in our MHD cohort during follow up (Table 2). The CV-event group had, indeed, a higher prevalence of prior CAD history, DM, OSA and pre-dialytic SpO2 value, respectively (all _p_-values < 0.05) (Table 3). In the univariate Cox regression model for all-cause mortality, our results demonstrated MHD patients with DM history and lower pre-dialytic levels of SpO2 had greater risks for all-cause death [HR: 0.895 ((95% CI: 0.821-0.975), _p_-values < 0.05; 2.518 (95% CI: 1.067-5.942), _p_-values < 0.05; respectively) (Table 4). Furthermore, DM, CAD, OSA, and lower levels of pre-dialytic SpO2 had greater risks for CV death (all _p_-values < 0.05). After adjusting above significant risk factors in the multivariable Cox regression model, however, OSA lost the predictive power for all-cause and CV mortality (Table 5). In view of this, OSA and lower levels of SpO2 may share the common pathway in the pathogenesis of CV death that OSA patients require more frequent screening for SpO2 levels [16; 17]. We, therefore, applied 95% as the cut-off value for abnormal pre-dialytic SpO2 in the secondary analysis. Through multivariate adjustment in the Cox regression model, the cumulative survival curve for CV mortality demonstrated the association between the abnormal pre-dialytic level of SPO2 and CV mortality remained robust (_p_-value < 0.05) (Figure 2). Hypoxemia during hemodialysis has been well-studied in the past years, and several mechanistic explanations have been proposed. Intradialytic hypoxemia has been observed in patients while sleeping during the session of HD [4]. Because CO2 may diffuse from the blood into the dialysate, a decrease in respiratory drive has been incriminated, leading to reduced partial pressure of CO2 and the pH in the blood. Given that breathing is tightly controlled by chemoreceptors correlated with the levels of CO2 and PH in the blood and cerebrospinal fluid, a reduction in circulating CO2 partial pressure may result in hypoventilation and hypoxemia [4]. Fluid overload, lung edema, heart failure and CAD-induced pulmonary congestion may affect oxygen diffusion, resulting in reduced blood oxygenation. Accordingly, the therapeutic strategy of approaching dry weight could improve systemic oxygenation. Nonetheless, monitoring the intradialytic change of blood oxygenation may be too late. To deploy a timely and effective therapeutic strategy in preparation, a robust screening tool to warn clinicians in advance is crucial for the MHD population. To avoid intradialytic events, pre-dialytic SpO2 measurement serves as an optimal medical parameter to improve patient safety and deliver early detection for high-risk subjects in the post COVID-19 era. Why should we pay more attention to hypoxia in the post COVID-19 era? The angiotensin-converting enzyme 2 (ACE2) is SARS-CoV-2 receptor of the cell, which is expressed in the carotid body, the chemoreceptors to sense oxygen [1]. Meanwhile, ACE2 receptors are distributed in nasal mucosa. A total of two thirds of patients with COVID-19 suffer from anosmia-hyposmia [18]. Furthermore, the olfactory bulb accounts for a passage along which certain Coronavirus enter the central nervous system [19]. Emerging evidence indicates a link between silent hypoxemia and the thrombi formation within the CV system and pulmonary vasculature [20]. Increased thrombogenesis and vascular inflammation could lead to severe hypoxemia and subsequent CAD and CV deaths in various populations [5; 14; 21; 22; 23]. A recent study specifically states that the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and the potent vasoconstrictor endothelin-1 (ET-1) are intricately involved in atherosclerotic plaques formation and assisting in detecting the CV risk in OSA subjects, respectively [24].