A pain from the nose to the head: neurological commitment during long COVID

Abstract

Background: Long COVID is a debilitating illness with multi-systemic symptoms that affects at least 10% of individuals who have had COVID-19. Symptoms include respiratory, dermatological, gastrointestinal, cardiovascular, and most frequently reported, neurological sequelae. The most common neurological manifestations include fatigue, brain fog, memory issues, attention disorder, and headaches. Methods: In this review, we explore the current literature and highlight key findings regarding not only the clinical presentations of neurological commitment during long COVID but mainly the mechanisms that culminate in neuroinflammation, such as autoimmunity, viral reservoirs, and lack of surveillance of T-cells. Results: Neuroinflammation is a complex multicellular response that directly impacts microglial cells and includes inflammasome activation, trafficking of immune cells, and increased circulating autoantibodies, cytokines, and chemokines in the central nervous system, directly impacting the tissue homeostasis. This review provides important information beyond the clinical manifestations of long COVID. Here, we highlight multifactorial neuroinflammation as the main mechanism involved in long COVID, bringing together several studies that address the different mechanisms that culminate in inflammation of the central nervous system, and highlight possible biomarkers involved in this syndrome and potential therapeutic approaches that have been studied. Conclusion: Thus, this review strengthens research into long COVID and provides new possibilities for future studies.