SARS-CoV-2 infection in hamsters caused phase-dependent cardiac dysautonomia, with post-acute autonomic remodeling suppressed by early inhibition of innate immune signaling or oxidative stress.
Does SARS-CoV-2 infection alter cardiac autonomic function over time, and can early inhibition of innate immune signaling or mitochondrial oxidative stress suppress post-acute ANS remodeling in a hamster model?
Cardiac dysautonomia following SARS-CoV-2 infection is phase-dependent, and early inhibition of immune activation or mitochondrial oxidative stress can suppress post-acute autonomic nervous system remodeling.
Background Autonomic nervous system (ANS) dysfunction is a central feature of long COVID syndrome, yet little is known about how it develops during, and after, SARS-CoV-2 infection. Objective To characterize the time course of dynamic changes in linear and non-linear heart rate variability (HRV) measurements as indices of ANS function for up to two months after infection. Methods Hamsters implanted with radiotelemetry devices were inoculated with SARS-CoV-2. Electrocardiograms (ECG) and subpleural pressures were recorded before infection, and for 56 days post-infection (DPI). HRV and respiratory sinus arrhythmia (RSA) were analyzed and compared to the pre-infection baseline or Mock-infected controls. Ruxolitinib or mTEMPO were administered from 4 days pre-infection to 10 DPI to assess the effects of Jak/Stat inhibition or antioxidant treatment, respectively. Results ANS activity follows 3 phases after infection: i) a pronounced increase in parasympathetic activity relative to sympathetic activity during the acute phase of infection (1-4 DPI), ii) a decrease in overall ANS activity in the sub-acute phase (7-14 DPI), and iii) re-emergence of elevated sympathetic and parasympathetic inputs that continue to increase during the post-acute phase (28-56 DPI). The conclusions are corroborated by changes in RSA analysis, and acute pharmacological inhibition of cholinergic and β - adrenergic signaling. Post-acute ANS remodeling was suppressed by early inhibition of innate immune signaling or mitochondrial oxidative stress. Conclusion Cardiac dysautonomia following SARS-CoV-2 infection are phase-dependent. Inhibiting early immune activation or mitochondrial oxidative stress during the acute phase offers a strategy to suppress post-acute ANS remodeling that could contribute to long COVID syndrome.
Liu et al. (Mon,) conducted a other in SARS-CoV-2 infection (COVID-19). SARS-CoV-2 infection (with or without Ruxolitinib or mTEMPO) vs. Pre-infection baseline or Mock-infected controls was evaluated on Time course of dynamic changes in linear and non-linear heart rate variability (HRV) measurements and respiratory sinus arrhythmia (RSA). SARS-CoV-2 infection in hamsters caused phase-dependent cardiac dysautonomia, with post-acute autonomic remodeling suppressed by early inhibition of innate immune signaling or oxidative stress.
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