Neurocardiac Autonomic Dysfunction in Patients With Post-COVID-19 Condition: A Systematic Review and Meta-Analysis

Abstract

Background: Neurocardiac autonomic impairment with reduced heart rate variability (HRV) has been linked to SARS-CoV-2 infection and may persist in patients with post-COVID-19 syndrome. We synthesised meta-analytic data on HRV in post-COVID-19 syndrome.

Methods: Our systematic review and meta-analysis were guided by PRISMA standards. We used MEDLINE, Embase and Web of Science to identify non-randomised studies of HRV in patients with post-COVID-19 syndrome, conducted more than 3 months after infection and compared with healthy controls. The search covered the period from 01/2020 to 09/2023. We pooled data on the following HRV parameters: standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (rMSSD) and low-frequency to high-frequency ratio (LF/HF ratio). We applied a random effects model to account for heterogeneity. Risk of bias was assessed.

Results: From 856 initially identified records, we included 11 studies with a total of 1162 participants (593 post-COVID-19 patients and 565 healthy controls). We observed a trend toward lower HRV in post-COVID patients compared to controls, with small to medium effects for SDNN (SMD: 0.26, 95% CI: -0.03 to 0.56, p = 0.09), rMSSD (SMD: 0.11, 95% CI: -0.15 to 0.36, p = 0.41) and LF/HF ratio (SMD: -0.271, 95% CI: -0.61 to 0.07, p = 0.12). Moderate to high statistical heterogeneity of the effects was observed (I² = 83% for SDNN and 78% for rMSSD) and nine of 11 studies had a high risk of bias.

Conclusion: This meta-analysis suggests a possible association between post-COVID condition and alterations in neurocardiac autonomic function.

Keywords: COVID‐19; SDNN; autonomic nervous system; heart rate variability; post‐COVID conditions.