Searching for Etiopathophysiological Links for ‘Long Covid’

Abstract

Introduction: The Long Covid Syndrome: The post-acute sequelae of COVID-19 (PASC) or ‘Long Covid’ is a varying, relapsing, and remitting disorder that may follow recovery from acute infection with SARS-CoV-2 in some patients and last for a variable period. It has a protracted course culminating as lingering and incapacitating illness predisposed by certain constitutional factors and comorbidities. Akin to COVID-19, it primarily affects the respiratory system, but other systems such as neurologic, cardiologic, hepatic, renal and pancreatic, and cutaneous systems may be involved. As the infection can harm the immune system, various organs including lungs fall prey to the aberrant immune response. Etilogical Correlates and Pathogenesis: Long Covid is a multisystem disorder entailing multiple symptoms related to various organs. There are several theories about the etiology of Long Covid such as continuing presence of the virus and its biologically active fragments, reinfection with the same or a different variant, dysfunctional immune reactions leading to a chronic inflammatory state, an ill-defined condition exhibiting symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggestive of a complex, multisystem disorder, post-traumatic stress following severe COVID-19 illness and critical care issues, and aftermath resulting due to disturbed microbiota in gut, lungs, and other organs. Long Covid Pathogenesis: New Insights: The SARS-CoV-2 infection activates the humoral immunity leading to formation of antigen-antibody complexes and the antigen-antibody reactions, which may propagate to organ damage. Simultaneously, viral superantigens may overstimulate immune responses, inducing negative feedback loops to hamper immune function and allow the virus to persist and replicate. The persistent virus may contribute to long Covid. There may develop various autoantibodies causing tissue injury and fibrosis in lungs and other organs. The Altered Microbiome leading to the microbial dysbiosis has also been implicated in persisting inflammatory processes culminating as Long Covid. Conclusion: Therapeutic Considerations: With expanding awareness, it has been recommended that all patients after recovery from COVID-19 should have access to healthcare. On the practical side, there are being established clinics for people with Long Covid backed by multidisciplinary teams for supportive and specific treatment and follow up. The anti-fibrotic and anticoagulant agents may be helpful in preventing further lung damage and thrombotic episodes. The role of a COVID-19 vaccine in preventing Long Covid is not known, but it may be helpful in reducing morbidity. The strategies to improve the intestinal dysbiotic microbiota through probiotics and microbial transplant appear promising.