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COVID-19 is associated with long-term cardiovascular complications. Heart Rate Variability (HRV), a measure of sympathetic (SNS) and parasympathetic (PNS) control, has been shown to predict COVID-19 outcomes and correlate with disease progression but a comprehensive analysis that includes demographic influences has been lacking. The objective of this study was to determine the balance between SNS, PNS and heart rhythm regulation in hospitalized COVID-19 patients and compare it with similar measurements in healthy volunteers and individuals with cardiovascular diseases (CVD), while also investigating the effects of age, Body Mass Index (BMI), gender and race. Lead I ECG recordings were acquired from 50 COVID-19 patients, 31 healthy volunteers, and 51 individuals with cardiovascular diseases (CVD) without COVID-19. Fourteen HRV parameters were calculated, including time-domain, frequency-domain, nonlinear, and regularity metrics. The study population included a balanced demographic profile, with 55% of participants being under 65 years of age, 54% identifying as male, and 68% identifying as White. Among the COVID-19 patients, 52% had a BMI ≥ 30 compared to 29% of healthy volunteers and 33% of CVD patients. COVID-19 and CVD patients exhibited significantly reduced time-domain HRV parameters, including SDNN and RMSSD, compared to healthy volunteers (SDNN: 0.02 ± 0.02 s vs. 0.06 ± 0.03 s, p < 0.001; RMSSD: 0.02 ± 0.02 s vs. 0.05 ± 0.03 s, p = 0.08). In the frequency domain, both COVID-19 and CVD patients showed increased low-frequency (LF) power and lower high-frequency (HF) power compared to healthy volunteers (COVID-19 LF: 18.47 ± 18.18%, HF: 13.69 ± 25.80%; Healthy LF: 23.30 ± 11.79%, HF: 22.91 ± 21.86%, p < 0.01). The LF/HF ratio was similar in COVID-19 patients (1.038 ± 1.54) and healthy volunteers (1.03 ± 0.78). Nonlinear parameters such as SD1 were significantly lower in COVID-19 patients (0.04 ± 0.04 s vs. 0.08 ± 0.05 s, p < 0.01), indicating altered autonomic regulation. Variations in HRV were observed based on demographic factors, with younger patients, females, and non-white individuals showing more pronounced autonomic dysfunction. COVID-19 patients exhibit significant alterations in HRV, indicating autonomic dysfunction, characterized by decreased vagal tone and sympathetic dominance, similar to patients with severe cardiovascular comorbidities. Despite higher heart rates, the HRV analysis suggests COVID-19 is associated with substantial disruption in autonomic regulation, particularly in patients with specific demographic risk factors.
COVID-19 is associated with long-term cardiovascular complications. Heart Rate Variability (HRV), a measure of sympathetic (SNS) and parasympathetic (PNS) control, has been shown to predict COVID-19 outcomes and correlate with disease progression but a comprehensive analysis that includes demographic influences has been lacking. The objective of this study was to determine the balance between SNS, PNS and heart rhythm regulation in hospitalized COVID-19 patients and compare it with similar measurements in healthy volunteers and individuals with cardiovascular diseases (CVD), while also investigating the effects of age, Body Mass Index (BMI), gender and race. Lead I ECG recordings were acquired from 50 COVID-19 patients, 31 healthy volunteers, and 51 individuals with cardiovascular diseases (CVD) without COVID-19. Fourteen HRV parameters were calculated, including time-domain, frequency-domain, nonlinear, and regularity metrics. The study population included a balanced demographic profile, with 55% of participants being under 65 years of age, 54% identifying as male, and 68% identifying as White. Among the COVID-19 patients, 52% had a BMI ≥ 30 compared to 29% of healthy volunteers and 33% of CVD patients. COVID-19 and CVD patients exhibited significantly reduced time-domain HRV parameters, including SDNN and RMSSD, compared to healthy volunteers (SDNN: 0.02 ± 0.02 s vs. 0.06 ± 0.03 s, p < 0.001; RMSSD: 0.02 ± 0.02 s vs. 0.05 ± 0.03 s, p = 0.08). In the frequency domain, both COVID-19 and CVD patients showed increased low-frequency (LF) power and lower high-frequency (HF) power compared to healthy volunteers (COVID-19 LF: 18.47 ± 18.18%, HF: 13.69 ± 25.80%; Healthy LF: 23.30 ± 11.79%, HF: 22.91 ± 21.86%, p < 0.01). The LF/HF ratio was similar in COVID-19 patients (1.038 ± 1.54) and healthy volunteers (1.03 ± 0.78). Nonlinear parameters such as SD1 were significantly lower in COVID-19 patients (0.04 ± 0.04 s vs. 0.08 ± 0.05 s, p < 0.01), indicating altered autonomic regulation. Variations in HRV were observed based on demographic factors, with younger patients, females, and non-white individuals showing more pronounced autonomic dysfunction. COVID-19 patients exhibit significant alterations in HRV, indicating autonomic dysfunction, characterized by decreased vagal tone and sympathetic dominance, similar to patients with severe cardiovascular comorbidities. Despite higher heart rates, the HRV analysis suggests COVID-19 is associated with substantial disruption in autonomic regulation, particularly in patients with specific demographic risk factors.
Changes in cardiac function and morphology are reflected in variations in the electrocardiogram (ECG) and, in turn, in the cardiac risk indices derived from it. These variations have led to the introduction of normalization as a step to compensate for possible biasing factors responsible for inter- and intra-subject differences, which can affect the accuracy of ECG-derived risk indices in assessing cardiac risk. The aim of this work is to perform a scoping review to provide a comprehensive collection of open-access published research that examines normalized ECG-derived parameters used as markers of cardiac anomalies or instabilities. The literature search was conducted from February to July 2024 in the major global electronic bibliographic repositories. Overall, 39 studies were selected. Results suggest extensive use of normalization on heart rate variability-related indices (49% of included studies), QT-related indices (18% of included studies), and T-wave alternans (5% of included studies), underscoring their recognized importance and suggesting that normalization may enhance their role as clinically useful risk markers. However, the primary objective of the included studies was not to evaluate the effect of normalization itself; thus, further research is needed to definitively assess the impact and advantages of normalization across various ECG-derived parameters.
This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NCs), and induced sputum (IS) one year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February–May 2020), compared to COPD patients, model for “aged lung”. Data from questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male sex, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p < 0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p < 0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p ≤ 0.05) and NCs (p < 0.001) and were biologically older than COPD patients (p < 0.05). These findings suggest the need to monitor aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.
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