Uncertainties around post-COVID

One of the hypotheses for the pathophysiology of persistent post-COVID symptoms is a dysfunctional immune response to the virus. Some studies have shown persistent autoantibodies in patients with post-COVID condition.

One of the hypotheses for the pathophysiology of persistent post-COVID symptoms is a dysfunctional inflammatory response. Studies have shown an increase in inflammatory markers called cytokines or interferons. This hypothesis is based on the fact that cytokine levels are raised in the acute phase of the disease (the first 10 days) and that inflammation persists in the post-acute phase (second to fourth weeks). 

ACE2 receptors present in several organs of the body appear to be the gateway through which the SARS-CoV-2 virus enters cells. Direct or indirect invasion by the virus could be the cause of many of the symptoms associated with post-COVID. 

One of the hypotheses for the pathophysiology of persistent post-COVID symptoms is histamine intolerance or high levels of histamines in the body. This hypothesis is in line with a potential diagnosis of mast cell activation syndrome (MCAS). This syndrome has diagnostic criteria that are defined in the literature and should be discussed with the primary care physician.

How is MCAS treated ? 

If you have mast cell activation syndrome, you need to talk to your doctor. Antihistamines are the first-line treatment. A low-histamine diet is suggested by some experts. While there are no general recommendations, a specific diet can be tried as a treatment in some cases. It is also important to balance the benefits and drawbacks of each diet, as some of them are quite restrictive and deprive the body of essential nutrients. The diets should be followed in consultation with a health-care professional.
 

If other causes have been excluded, post-COVID symptoms that persist for more than 3 months could meet the criteria for fibromyalgia and be included in the same pathology. Fibromyalgia is characterized by persistent pain.
For a diagnosis of fibromyalgia, the following three conditions must be met: 

• Pain lasting at least 3 months 
• Pain and symptom severity measured by a health professional using validated scales 
• Any other cause of chronic joint pain must be ruled out.

The underlying pathophysiology of fibromyalgia is still under investigation. Post-COVID condition, with the large number of cases and the ability to identify the date of onset of symptoms in relation to the date of infection, may help to provide a better understanding of this syndrome
 

A recent study on a small sample (106 people) has shown that post-COVID patients have an altered microbiota, and that the profile of the gut microbiome is associated with different symptoms. These results open up an avenue of research into the association of microbiota and the development of post-COVID. However, more studies are needed to confirm these observations.

One of the hypotheses involves local inflammation or damage to blood vessel walls. Studies have shown microclots potentially resulting from blood vessel (endothelial) damage in patients with persistent post-COVID symptoms.
 

MIS-C, which stands for multisystem inflammatory syndrome in children, is also known as PIMS, or pediatric inflammatory multisystem syndrome. It is associated with COVID-19 but is distinct from post-COVID in terms of its pathophysiological mechanism, its clinical presentation and its management. 

It is a rare complication of COVID-19 that can occur in children and adolescents 3 to 6 weeks after the infection. It manifests itself as severe inflammation that can affect several organs and can be very serious. The symptoms of MIS-C (PIMS) are fever and general ill health. A rash, abdominal pain, diarrhea and conjunctivitis may also be present. If MIS-C is suspected, you should consult your pediatrician or the pediatric emergency unit urgently so that additional tests can be performed if necessary.
 

Another mechanism that may be responsible for post-COVID is autonomic nervous system (ANS) dysfunction. Indeed, dysautonomia is widely associated with post-COVID and is thought to contribute to the presence of numerous symptoms such as fatigue, orthostatic hypotension, tachycardia and digestive disorders. Moreover, a large study showed that autonomic nervous system dysfunction was present in more than 2/3 of post-COVID patients. However, the underlying mechanism explaining this dysregulation has yet to be elucidated.

Currently, there are two main hypotheses. The first is that the dysautonomia is directly due to the SARS-CoV-2 infection during the acute phase of the disease. The second is that the deregulation of the autonomic nervous system is a direct consequence of the autoimmune component of post-COVID. Indeed, autoantibodies have already been associated with autonomic dysfunctions leading to orthostatic hypotension or orthostatic postural tachycardias. Thus, the emergence of latent post-COVID autoimmunity could favour the presence of autoantibodies that would cause deregulation of the autonomic nervous system. This could have a direct consequence on the immune system and coagulation, both normally regulated by ANS, and which are also significantly impaired in post-COVID.
 

If other causes have been excluded, post-COVID symptoms that persist for more than 6 months could meet the criteria for chronic fatigue syndrome and be included in the same pathology. Currently, the difference is the identification of the trigger virus that leads to the persistent symptoms, which is not always possible with chronic fatigue syndrome. This syndrome is characterized by:

• A significant reduction in functional capacity lasting at least 6 months, often accompanied by profound fatigue that is new.
• Post-exertional malaise with worsening of symptoms following even light intellectual or physical effort that would have been tolerated before the onset of symptoms.
• Non-restorative sleep.

In addition, at least one of the following criteria is required for the diagnosis of chronic fatigue syndrome:

• Cognitive impairment (concentration or executive function)
• Orthostatic intolerance or intolerance to standing for long periods

These criteria are based on the Institute of Medecine definition. If these symptoms are present at least half of the time, chronic fatigue syndrome should be investigated using specific scales and making adjustments in daily life in line with daily energy reserves. The underlying pathophysiology of chronic fatigue syndrome is still under investigation. post-COVID condition, with the large number of cases and the ability to identify the date of onset of symptoms in relation to the date of infection, may help to provide a better understanding of this syndrome.

It is important to recognize that certain medical and psychosocial factors, including hospitalization, lack of support and difficulties in access to health care, can also contribute to the persistence of symptoms. In addition, some treatments can exacerbate symptoms such as fatigue or sleep problems. Interdisciplinary care is essential in the management and follow-up of people with post-COVID symptoms.