Understanding Post-COVID-19: Mechanisms, Neurological Complications, Current Treatments, and Emerging Therapies

Kevin Zambrano,1– 5 Karina Castillo,1,2 Sebastian Peñaherrera,1,2,4 Henry C Vasconez,1,2 Andrés Caicedo,1– 4 Antonio WD Gavilanes1,3 1Department of Health Sciences, Universidad San Francisco de Quito USFQ, School of Medicine, Quito, Ecuador; 2Institute of Biomedical Research (Ibiomed), Universidad San Francisco de Quito USFQ, Quito, Ecuador; 3School for Mental Health and Neuroscience (Mhens), Maastricht University, Maastricht, the Netherlands; 4Mito-Act Research Consortium, Quito, Ecuador; 5Neuroscience Institute, Universidad San Francisco de Quito USFQ, Quito, EcuadorCorrespondence: Andrés Caicedo; Antonio WD Gavilanes, Email [email protected]; [email protected]: COVID-19, a highly infectious disease, caused a worldwide pandemic in early 2020. According to the World Health Organization (WHO), COVID-19 has resulted in approximately 774 million cases and around 7 million deaths. The effects of COVID-19 are well known; however, there is a lack of information on the pathophysiological mechanisms underlying the symptoms that comprise Post-Acute COVID-19 Syndrome (PACS) or Long COVID-19. Neurological sequelae are common, with cognitive dysfunction being one of the foremost symptoms. Research indicates that elevated inflammatory levels and increased oxidative stress may play a role in the etiology and severity of PACS. Treatment options are extremely limited, and there is no consensus among the medical and scientific communities on how to manage the disease. Nevertheless, many scientists advocate for using antioxidants for symptomatic therapy and cognitive behavior therapy for supportive care. Additionally, current research aims to ameliorate several aspects of the inflammatory cascade. This review highlights the intracellular and extracellular pathways crucial to the neurological manifestations of PACS, providing valuable information for healthcare professionals and scientists. Given the complex nature of PACS, understanding these pathways is essential for developing new treatment options. Assessing PACS is challenging, and reviewing current therapeutic options while proposing a triad of potential therapeutic elements will add value to clinical assays and guidelines. Current therapeutic strategies, such as antioxidants/vitamin supplements, neurogenic stem cell therapy, and mitochondrial therapy, could be combined to enhance their effectiveness. Future research should focus on validating these approaches and exploring new avenues for the effective treatment of PACS. Keywords: post-acute COVID-19 syndrome, PACS, long COVID-19, cognitive dysfunction, mitochondrial therapy