Neurological Effects of COVID-19 and Its Treatment/Management

*John Teibo, Abolaji Olagunju, Festus Atiba, Olabode Omotoso, Titilade Teibo, Ahmad Babalghith and Gaber Batiha*

### **Abstract**

The impact of COVID-19 is significant in the body system, one of which is the central nervous system (CNS) involved in controlling all aspects of human behavior and coordination. This shows the need to assess from various studies in human and animal models the neurological effects of this virus. Some of the reported effects include loss of taste and smell, headaches, delirium, dizziness, ischemic stroke, and brain inflammation. It is essential to review the acute, chronic or transient neurological effects. This will enhance and/or improve treatment designs and management modalities for the COVID-19. We critically revise the literature and contribute to the body of knowledge in this line of research. Here in this chapter, we highlighted the various neurological disorders caused by COVID-19 and examined the relationship between the neurological systems and COVID-19. As well as evaluate current treatment/management modalities including vaccines and prospects for the future.

**Keywords:** COVID-19, SARS-CoV-2, neurological disorders, neurological symptoms, treatment/management modalities

### **1. Introduction**

COVID-19 causative virus (SARS-CoV-2) affects many body organs and systems to induce its pathogenesis. The disease is severe in people with comorbidities such as obesity, diabetes, hypertension, chronic respiratory disease, cerebrovascular disease, and chronic kidney and liver disease [1].

In neural tissues, the mechanism of invasion is well-established. It involves the interaction of ACE2 (Angiotensin-converting enzyme 2) receptors and spike protein. SARS-CoV-2 enters the nervous system via neurotropism, hematological dissemination, vasculotropism, and cytokine storm [2, 3].

Some of the common neurological symptoms of SARS-CoV-2 include CNS symptoms; (dizziness, delirium, confusion, prominent agitation, and dizziness), acute cerebrovascular disease, and epilepsy; PNS symptoms; ageusia (loss of sense of taste), hypogeusia (reduction in the ability to taste), anosmia (inability to smell), hyposmia (reduction in the ability to smell), and neuralgia (painful sensation in the body) and skeletal muscular symptoms: myalgia/fatigue and muscle injury [3, 4].

Many bioactive compounds have been reviewed for their antiviral effects which may have both preventive and curative effects [5]. Mainstay pharmacological/nonpharmacological interventions for prevention, management, and treatment include COVID-19 vaccines, remdesivir [6], SARS-CoV-2 targeting monoclonal antibodies such as Casirivimab and Imdevimab, Immune modulators (Baricitinib), immunosuppressive therapy as well adherence to public health guidelines such as handwashing, use of alcohol gels and face masks, etc.

In this chapter, we highlighted various neurological disorders and symptoms caused by COVID-19 and examined the relationship between the neurological systems and COVID-19. Additionally, we evaluated current therapies including the administration of vaccines, anti-virals, and their prospects for future applications.

## **2. COVID-19**

The novel coronavirus disease (COVID-19) has been a dire threat to public health, the global economy, and human co-existence since its first report in Wuhan, China in 2019 [7]. Globally, as of 2nd June 2022, there have been 6,293,414 deaths due to COVID-19 out of 528,275,339 confirmed cases. To curtail the menace of COVID-19, 11,947,644,522 vaccine doses have been reported administered globally [8]. Prior to the development and administration of vaccines, a number of preventive measures (hand-washing under running water, use of alcohol-based hand sanitizer, social distancing, wearing of face mask, etc.) were put in place by health regulatory bodies to manage the transmission of the disease [7]. These measures were evaluated to study compliance and effectiveness in curbing the spread of the virus [9–11]. Although the global incidence and mortality rate has declined, adherence to preventive measures and vaccination is still encouraged.

COVID-19 severity has been reported in elderly patients and those with comorbidities (obesity, diabetes, hypertension, chronic respiratory disease, cardiovascular disease, cerebrovascular disease, chronic kidney, and liver disease) [1, 12]. Due to the novelty of the disease, the possibility of other long-term effects is still unknown. However, those with severe cases of infection can develop acute or chronic effects (graphical abstract) such as chronic fatigue syndrome, complications of the heart, lung, and kidney, neurological defects (loss of taste and smell, delirium, headaches, brain inflammation, stroke, and Guillain-Barre syndrome) [12, 13]. This calls for a need for closer monitoring and more research into the aftermath effect of the COVID-19, even in well-managed patients.

### **3. Mechanism of neurological pathology**

The SARS-CoV-2 respiratory indices are well known and reported. Recently, there has been a significant increase in evidence showing anosmia (complete loss of smell) as a SARS-CoV-2 symptom, indicating a high level of neurological involvement following the infection and also SARS-CoV-2 having neuro-invasive properties. Studies suggest that SARS-CoV-2 enters the central nervous system (CNS) in either of the two ways; through systemic vascular dissemination or across the cribriform plate of the ethmoid bone, which might have consequences concerning anosmia as experienced by the SARS-CoV-2 patients [14]. The virus invades the neural tissue once in the systemic circulation due to its neurotropism properties and then, binds and interacts

#### *Neurological Effects of COVID-19 and Its Treatment/Management DOI: http://dx.doi.org/10.5772/intechopen.105730*

with ACE2 (Angiotensin-converting enzyme 2) receptors in the endothelium capillary via the spike proteins [14, 15]. Previously, ACE2 has been shown to be expressed in the upper and lower epithelium of the airways together with the CNS endothelial capillary [16]. One of the studies conducted evaluating SARS-CoV-2 spike glycoprotein structural integrity showed an approximately 20- a fold affinity increases to ACE2 when compared to the spike protein of the sister virus SARS-CoV-2 [17]. However, using BLASTp, the spike proteins of the two sister viruses are structurally similar but not identical, explaining the differences in the neurological prevalence. Meanwhile, not all the human cell lines that express ACE2 are susceptible to the novel coronavirus infection. Nevertheless, several neurological manifestations of the SARS-CoV-2 infection should be given absolute attention together with its well-understood respiratory index.

#### **3.1 Stroke**

Stroke is now common, developing, and/or potentially devastating SARS-CoV-2 infection complication [18]; about 2–6% of hospitalized COVID-19 patients have developed an acute cerebrovascular event [19]. In 2020, a large vessel stroke was reported in five patients (< 50 years of age) infected with SARS-CoV-2 [20]. Studies on the thromboembolic complications rate in SARS-CoV-2 patients showed 1.6% [21] and 2.5% [22] reported ischemic stroke occurrences. Klok and Lodigiani showed that the thrombotic complications were significantly high for their respective institutions. However, there are other risk factors predisposing COVID-19 patients to thromboembolic stroke development beyond the usual metabolic and cardiovascular co-morbidities. At this moment, various mechanisms of SARS-CoV-2 induced stroke have been reported including myocardial damage with cerebral embolism, coagulopathy, or pre-existing atheroma plaque destabilization [23]. The viral invasion led to thrombosis by activating immune response involving platelets, endothelium, and coagulation. Furthermore, SARS-CoV-2 causes cytokine storms resulting in increased D-dimers, affecting coagulation, and inducing stroke. Also, viral invasion can lead to heart damage, resulting in viral myocarditis and finally cardioembolic stroke. Inflammation can destabilize the fibrous capsule surrounding the atheroma plaque, eventually, exposing the thrombogenic clotting material, initiating arteries clogging and thus, causing a stroke [23].
