Is SARS-CoV-2 the only cause of long-COVID?

Abstract

Around 10% of adults infected with SARS-CoV-2 that survive a first episode of COVID-19 appear to experience long-term clinical manifestations. The signs and symptoms of this post-acute COVID-19 syndrome (PACS) include fatigue, dyspnea, joint pain, myalgia, chest pain, cough, anosmia, dysgeusia, headache, depression, anxiety, memory loss, concentration difficulties, and insomnia. These sequelae remind the constellation of clinical manifestations previously recognized as myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). This condition has been described following distinct infectious events, mostly acute viral illnesses. In this way, the pathophysiology of PACS might overlap with mechanisms involved in other post-infectious fatigue syndromes. The risk of PACS is more frequent in women than men. Additional host genetic factors could be involved. There is a dysregulation of multiple body organs and systems, involving the immune system, the coagulation cascade, endocrine organs, autonomic nervous system, microbiota-gut-brain axis, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-thyroid axis, etc. Hypothetically, an abnormal response to certain infectious agents could trigger the development of post-infectious fatigue syndromes.

Pituitary and SARS CoV-2: An unremitting conundrum

“…Approximately 10% of patients recovering from COVID-19 may experience persistent, sometimes debilitating clinical manifestations. These include neuropsychiatric manifestations as depression, anxiety, loss of memory, sleep and concentration problems, anosmia, ageusia, respiratory ones, as dyspnea, chest pain, persistent cough, muscle and joint pain or general (fatigue) symptoms [141] . Similar heterogeneous constellation of symptoms can persist after many other viral illnesses.…”

Genomic Determinants of Long COVID

“…This is in part due to lack of de nitive datasets that allow clear-cut patients. The de nition of clinical symptoms and signs still remains tenuous [4], which makes it di cult to amass datasets su ciently different and large enough to enable genetic association. Because of these limitations, we have taken a different approach.…”

“…The Centers for Disease Control and Prevention (CDC), suggests the need to expand the evidence base to estimate both the risk of experiencing post-COVID conditions and the number of people experiencing them by demographic group [3]. Although there are grounds to believe that a genetic signature might be involved in Long COVID [4], to date no genetic markers have been reported. Identi cation of genetic traits predisposing people to Long COVID could help prevent post-COVID conditions.…”

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

“…In addition to fatigue, these diseases are frequently accompanied by a variety of overlapping symptoms, such as cognitive impairments, sleep disturbances, brain fog, concentration/memory impairments, and muscle pain. These symptoms can be attributed, at least partially, to mitochondrial dysfunction, which can have an impact on brain energy metabolism [ 38 , 39 ] ( Figure 1 ).…”