Letter to the Editor
We are writing to highlight the potential for a post-viral syndrome to manifest following COVID-19 infection as previously reported following Severe Acute Respiratory Syndrome (SARS) infection, also a coronavirus.1 After the acute SARS episode some patients, many of whom were healthcare workers went on to develop a Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) - like illness which nearly 20 months on prevented them returning to work.2 We propose that once an acute COVID-19 infection has been overcome, a subgroup of remitted patients are likely to experience long-term adverse effects resembling CFS/ME symptomatology such as persistent fatigue, diffuse myalgia, depressive symptoms, and non-restorative sleep.
Post-mortem SARS research indicated the virus had crossed the blood brain barrier into the hypothalamus via the olfactory pathway.2 The pathway of the virus seemed to follow that previously suggested in CFS/ME patients, involving disturbance of lymphatic drainage from the microglia in the brain.3One of the main pathways of the lymphatic drainage of the brain is via the perivascular spaces along the olfactory nerves through the cribriform plate into the nasal mucosa.4 If the pathogenesis of coronavirus affects a similar pathway, it could explain the anosmia observed in a proportion of COVID-19 patients.
This disturbance leads to a build-up of pro-inflammatory agents, especially post-infectious cytokines such as interferon gamma, and interleukin 7,5 which may affect the neurological control of the ‘Glymphatic System’ as observed in CFS/ME.3 The build up of cytokines in the Central Nervous System (CNS) may lead to post viral symptoms due to pro-inflammatory cytokines passing through the blood brain barrier in circumventricular organs such as the hypothalamus, leading to autonomic dysfunction manifesting acutely as a high fever and in the longer term to dysregulation of the sleep/wake cycle, cognitive dysfunction and profound unremitting anergia, all characteristic of CFS/ME. As happened after the SARS outbreak, a proportion of COVID-19 affected patients may develop a severe post viral syndrome we term ‘Post COVID-19 Syndrome’ - a long term state of chronic fatigue characterised by post-exertional neuroimmune exhaustion.6
In a contracted future economy, managing these likely Post COVID-19 syndrome cases, in addition to existing CFS/ME cases will put additional burden on our already hard pressed healthcare system. We suggest that priority is given to exploration of pragmatic relatively low cost techniques to treat post-viral fatigue, to alleviate symptoms and improve quality of life for those affected by the longer term sequelae of COVID-19.