**6. Indirect effects of SARS-CoV-2 in CNS**

There are several neurological symptoms and diseases that are associated with COVID-19. These include Guillain-Barré-syndrome (GBS), myasthenia gravis (MG), opsoclonus-myoclonus syndrome (OMS) and others (**Table 2**). In these diseases, a direct effect of SARS-CoV-2 and subsequent tissue damage is unlikely and other mechanisms are hypothesized. Such potential mechanisms are molecular mimicry and bystander activation [61, 62]. Molecular mimicry means that there may be the structural similarity between virus sequences or/and domains and structures or/and sequences of the individual [63]. Potentially, these similarities can result in an immune response that is not only directed against parts of the virus but also against self-proteins, for example, the nicotinic acetylcholine receptor (nAChR) that is the autoantigen in myasthenia gravis. In bystander activation, the immune response triggered by a viral infection can cause an activation of an immune response directed against self-antigens that will also result in autoimmune disease. The list of possible autoimmune manifestations due to the affection of SARS-CoV-2 and COVID-19 is growing. This is also the case for autoimmune neurological manifestations (**Table 2**). There is increasing knowledge regarding the structural requirements for induction of autoimmune disease after viral infection with SARS-CoV-2.

Cytokine storm induced by infection with SARS-CoV-2 and COVID-19 can lead to multiple organ damage and potentially induction/boosting of an autoimmune immune response [54].

## **7. Chronic fatigue syndrome and COVID-19**

Some patients that had COVID-19 subsequently develop long-COVID-19 or also named post-COVID-19 [64, 65]. Many of these patients suffer from strong fatigue. The condition is clinically like chronic fatigue syndrome (CFS) also named myalgic encephalomyelitis (ME). In CFS there is a strong indication that there is an energy failure on the cellular level that can result in rapid exhaustion and fatigue. In addition, there are changes in certain immune cell types that can result in increased susceptibility to infection. Changes in lymphocyte stiffness, monocyte size, neutrophil size and deformability, and heterogeneity of erythrocyte deformation and size were found [66]. The exact mechanism of how COVID-19 is resulting in subsequent CFS is not known at present. The diagnosis is mainly based on clinical characteristics with the presence of abnormal fatigue. Presently, there are no specific markers that allow a laboratory-based diagnosis. Usually, CSF analysis does not show distinctive features. There are no approved pharmaceutical options for the treatment of fatigue associated with long-COVID-19 or post-COVID-19. Treatment involves mild physical endurance training.

### **8. Treatment of COVID-19**

Treatment options can be separated according to treatment to counteract viral replication and viral virulence of SARS-CoV-2 and treatment options to counteract and treat organ damage due to consequences of the infection with SARS-CoV-2 (**Table 3**). Remdesivir is a treatment option that counteracts viral replication [67]. This is a drug that has been initially developed for fighting Ebola. It has been shown to be efficacious if given early after infection with SARS-CoV-2. In combination with the Janus-kinase inhibitor baricitinib increased efficacy could be demonstrated [69].


### *Neuroimmunology and Neurological Manifestations of COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.103026*

