Long COVID or post-acute sequelae of COVID-19 is defined as an after-effect of acute COVID-19 infection. Its broad clinical symptoms include brain fog, shortness of breath, fatigue, joint, chest, or muscle pain, dysautonomia and neuropsychiatric symptoms such as anxiety, depression and post-traumatic stress disorder. It is estimated that 1 in every 5 COVID-19 survivors exhibit symptoms within the Long COVID bracket. An array of risk factors such as smoking habit, age, obesity, female sex, and prior hospitalization may increase the probability of a person developing Long COVID. While the underlying mechanisms of Long COVID remain elusive, we examine the various possible pathophysiologies involved in Long COVID. We take up impactful neuropsychiatric issues as another spectrum of Long COVID symptoms and the likely effect of various forms of COVID-19 vaccines. In this review, the focus will be on the main mechanisms associated with the development of long COVID, which include latent Epstein-Barr virus reactivation, molecular mimicry, virus persistence, autoantibodies, and mitochondrial dysfunction. Understanding these mechanisms shed light on the continued persistence of COVID-19 related symptoms long after the resolution of acute infection. For instance, the reactivation of Epstein-Barr virus in the immunocompromised context seen post-acute SARS-CoV-2 infection could lead to the symptoms commonly observed in Long COVID such as fatigue and brain fog. The Epstein-Barr virus could possibly disrupt mitochondrial function, explaining the fatigue commonly observed in Long COVID patients. Other factors such as continued presence of viral particles in specific areas such as the gut may result in continued inflammation, leading to manifestations such as fatigue, cognitive impairment and gastrointestinal dysfunction. Additionally, heightened and persistent presence of autoantibodies post-acute infection results in persistent symptoms and could potentially trigger the onset of autoimmune disorders. We also aim to revisit the diverse and prolonged effects of the COVID-19 pandemic that continue to affect the well-being and quality of human life.
