key: cord-0984269-dg8ls8n4
authors: Perrin, Ray; Riste, Lisa; Hann, Mark; Walther, Andreas; Mukherjee, Annice; Heald, Adrian
title: Into the looking glass: Post-viral syndrome post COVID-19
date: 2020-06-27
journal: Med Hypotheses
DOI: 10.1016/j.mehy.2020.110055
sha: 5d6e51d225a302057a601ae03ec8c5c3ecc9c6ae
doc_id: 984269
cord_uid: dg8ls8n4

nan

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. 3 One 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 postinfectious cytokines such as interferon gamma, and interleukin 7, 5 which have been hypothesized to 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 It may be that early intervention and supportive treatments at the end of the acute phase of COVID-19 can help overcome acute phase symptoms and prevent them in becoming longer-term consequences. Without this, in a contracted future economy (at least in the short to intermediate term), managing these likely Post COVID-19 syndrome cases, in addition to existing CFS/ME cases will place additional burden on our already hard pressed healthcare system.

In the light of this and similar cases and in the context of the available evidence for SARS, we suggest that priority should be given to examine the prevalence of fatigue related symptoms following COVID-19 infection and to explore pragmatic relatively low cost techniques to treat post-viral fatigue, to alleviate symptoms and improve the quality of life for those affected by the longer term sequelae of COVID-19.

Let's start the preparations now for what may come in due course.

RP developed the Perrin Technique which is described here. No other author has any competing interests.

Ethical Approval:

No ethical approval was required for this piece of work.

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Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Myalgic encephalomyelitis: international consensus criteria

Development of a measure of symptoms in chronic fatigue syndrome: the profile of fatigue related symptoms (PFRS)

Contributor statement: Dr. Raymond Perrin led on the writing of the article with contributions in terms of literature search and current perspective from Dr. Lisa Riste, Dr Andreas Walther and Dr. Adrian Heald. Mark Hann provided statistical advice regarding PFRS change scores

Annice Mukherjee provided further academic input and also senior review. All authors contributed to the final version of the manuscript and approved the final version. Funding: There was no external funding for this work