Editorial: An Update on Neurological Disorders Post COVID-19 Infection Vol 2: cardiovascular effects, neuro-cardiac and neuro-respiratory autonomic dysfunctions

Beatrice Paradiso^*Giulia Ottaviani

• Lino Rossi Research Center, Department of Biomedical, Surgical and Dental Sciences, Faculty of Medicine and Surgery, University of Milan, Milan, Italy

Another well-documented effect of prolonged COVID is autonomic nervous system impairment. Several studies have focused on this topic, highlighting its clinical symptoms and therapeutic applications. Pierson et al. [4] provide a comprehensive overview of pharmaceutical alternatives for postural orthostatic tachycardia syndrome (POTS), a common finding in PASC patients, emphasising the potential of beta-blockers, ivabradine, and midodrine. Cantrell et al. [5] present a distinct post-COVID POTS phenotype characterised by concomitant migraines, fatigue, and gastrointestinal problems, highlighting the frequent overlap of autonomic and systemic symptoms. Liviero et al. [6] provide crucial longitudinal data suggesting that even those with minor illnesses can undergo sustained changes in autonomic regulation, as demonstrated by changes in heart rate variability. These findings challenge earlier assumptions that only severe COVID-19 cases carry long-term risk and call for vigilance in post-infection follow-up.Theiler et al. [7], in their report of an immune-mediated example of orthostatic hypotension, emphasise the importance of identifying underlying pathophysiological factors in dysautonomia patients. Their findings show that immunological mechanisms may play a larger role in post-COVID autonomic problems than previously thought, necessitating additional research into autoantibody patterns and inflammatory mediators. The issue of immunological and vascular interaction is critical to understanding extended COVID. Mehboob et al. conducted two complimentary studies on the roles of Substance P [8] and ACE-II dysregulation [9] in prolonging endothelium damage and inflammation. Their research helps to explain how neuropeptide signalling and poor vascular homeostasis can contribute to persistent symptoms. One especially informative graphic from their analysis (Figure 1) depicts the chain of events that lead to endothelial injury, hypoxia, and neuroinflammation, potentially indicating a unifying mechanism for cognitive symptoms in neuro-PASC. Pommy et al.'s findings (3) support this vascular hypothesis by emphasising the importance of decreased cerebrovascular response as a source of cognitive disruption and identifying potential interventional targets for future treatment trials. Systemic inflammation and metabolic imbalance are also identified as important contributors in PASC. Rus [10] explores the interaction of the serotonin and kynurenine pathways, hypothesising that disturbance in these metabolic circuits may be responsible for many of the neuropsychiatric symptoms seen in long-term COVID. The kynurenine pathway is known to be implicated in neuroinflammation and neurotoxicity, and its dysregulation could operate as a link between immune activation and mental health issues. This line of research opens the door to new biomarkers and tailored treatments for restoring metabolic and immunological balance. Clinical outcomes remain a major source of concern, particularly among disadvantaged groups. Desouky et al. [11] analyse hospitalised patients with pre-existing neurological diseases and find that those with dementia, epilepsy, and chronic headaches had a higher mortality rate. These findings highlight the need for better surveillance and targeted care techniques for at-risk persons during and after COVID-19. The study demonstrates how pre-existing brain vulnerability might increase the risk of systemic infections, emphasising the importance of integrative care measures. While understanding the underlying mechanisms of PASC is critical, the importance of encouraging recovery and resilience cannot be emphasised. Several articles emphasise the necessity for a comprehensive, personalised approach to post-COVID care. Behavioural and rehabilitative treatments, as well as consideration of lifestyle and psychological factors, may play an important role in recovering function and quality of life. Understanding why some people heal more completely than others could help guide future clinical management and research objectives. Longitudinal research and systematic rehabilitation programmes will be required in the future years to determine the best strategies for addressing these chronic symptoms. The articles in this Research Topic demonstrate the multidimensional character of PASC and the crucial need for multidisciplinary research and care. These contributions go beyond mere description, charting a course for mechanistic clarity, improved diagnoses, and more effective therapies. They reflect the scientific community's collaborative endeavour to not only study the effects of COVID-19, but also to provide practical tools and pathways for recovery. As editors, we are grateful to the writers and reviewers for their careful work in making this book possible. We hope it will educate, inspire, and assist the many professionals and patients navigating the challenges of post-COVID disorders."Figure 1 adapted from Mehboob et al., 2023 [9], with permission"