Post-COVID19 syndrome, a model of post-viral chronic fatigue syndrome.

Post-COVID-19 syndrome is a relatively new disorder and, therefore, experience in diagnosing and treating it is limited. When the SARS-CoV-2 epidemic emerged and became a global pandemic, most efforts were directed at the acute consequences of systemic inflammatory damage, which causes high morbidity and mortality. Up to 40% of people with SARS-CoV-2 never develop symptoms, while about 80% of those symptomatic have a mild illness that does not require hospitalization.

On the other hand, about 20% require hospitalization, but only 5% develop progressive dyspnea and require admission to an intensive care unit. In addition to lung damage, COVID-19 can also damage other organs such as the brain, heart, liver and digestive tract, kidneys and blood vessels. This can confer a multisystem scenario with high long-term repercussions.

According to WHO, the time from onset to clinical recovery for mild cases was approximately 2 weeks and that recovery took 3 to 6 weeks for critical illness. Prolonged COVID can involve different syndromes; in some patients the debilitating symptoms persist for weeks or even months and in others they will never disappear.

The most common feature of Post-COVID-19 syndrome is that despite overcoming the acute phase of COVID-19 and having no evidence of COVID-19 activity, COVID symptoms such as fatigue, body aches, shortness of breath, difficulty concentrating/memory, exercise intolerance, headache and difficulty sleeping and autonomic nervous system disturbances persist and that patients have not regained their pre-COVID level of health and functional status after six months.

This induces a multidimensional scenario with physical and neurocognitive fatigue, which does not improve with rest and causes exercise intolerance, cognitive symptoms (impaired concentration and memory) and dysautonomia with dizziness, orthostatic hypotension, postural instability, inappropriate tachycardia and syncope. If this pathological fatigue lasts more than 6 months and decreases overall individual activity by more than 50%, and is accompanied by systemic symptoms, it is considered as a specific entity called “Chronic Fatigue Syndrome / Myalgic Encephalomyelitis” (CFS / ME).

There is progressive evidence that some patients may develop CFS/ME after COVID-19. In this sense, SARS-2 virus would be a triggering factor, similar to what happened in other post-viral CFS models such as secondary to Epstein-Barr infection, Cytomegalovirus, Hepatitis B and C virus and, Human Herpesvirus-6, Dengue and Ebola among others.

Post-COVID-19 syndrome would be a complex multifactorial disease with multiple interacting immunogenetic and environmental factors. The common pathomechanisms mediating the pathophysiology of fatigue and COVID-19 are the sum of systemic inflammatory response with multi-organ damage including limbic system dysfunction and viral persistence. Its pathogenesis would be similar to that of central sensitivity syndromes (CSS).

Genetically mediated personal susceptibility regulates the nature and intensity of the disease, leading to persistence of symptoms. Limbic neuroinflammatory dysregulation produces systemic symptoms with central fatigue, neuropathic pain, sleep and mood disorders, neuroendocrine, autonomic and inflammatory dysregulation resembling CFS/ME and SSCs.

This disorder has followed previous coronavirus infections by SARS and MERS, at a rate of around 20%. In Catalonia, an AQuAS systematic review supports that up to one third of COVID-19 patients with minor acute symptoms could develop Post-COVID-19 syndrome, in the context of post-viral chronic fatigue syndrome.

People who have had CFS/ME are more likely to get it again and the concern is that CoV-2 and other future infections may cause more outbreaks. Dr. Anthony Fauci has speculated that many patients with Post-COVID-19 syndrome will develop CFS/ME. So the similarity between Post-COVID-19 syndrome and chronic fatigue syndrome and the importance of proper diagnosis and treatment is evident.

In this sense, the clinical experience provided by the study of chronic fatigue syndrome in specialized units of both public and private medicine is very important for the professionals involved in them. With an interdisciplinary and multi-collaborative approach, to try to reduce the significant disability that post-COVID-19 syndrome can cause and to consider specific therapeutic interventions.