COVID-19 is a complex disease, affecting various organs including the respiratory system, kidneys, liver, heart, skin, and brain, with a wide range of clinical symptoms including neurological signs caused by SARS-CoV-2 [10], which compelled us to investigate the effects of this pandemic on patients with neurological presentations hospitalized at Fayoum University Hospital in light of the possibility that COVID-19 might increase the frequency of cases with neurological complications secondary to COVID-19 infection in comparison to the years before this era, as well as what are the most common neurological complications secondary to COVID-19 vaccinations.

The patients with confirmed COVID-19 infection who were hospitalized at the Neurology Department of Fayoum University Hospital accounted for 44.91% of the study's participants, which was similar to findings from earlier multicentric studies conducted in Egypt [11] as well as Brazil [12]. Contrary to these findings, a retrospective study of a large group in Northern Italy [13] found that the percentage of COVID-19 patients hospitalized with neurological problems was approximately 20%. The difference in percentages might be explained by rachial and ethnic susceptibility to SARS-CoV-2 infection and its consequences.

Regarding their clinical characteristics, patients hospitalized with neurological disorders during the pandemic era tended to be middle-aged, diabetic, and smokers in comparison to pre- and post-pandemic era, which was consistent with earlier findings [3, 11, 14]. Diabetes mellitus and smoking were thought to make COVID-19 infection worse, making patients more likely to require hospitalization and develop neurological sequelae. SARS-Cov-2 infection was reported to worsen diabetes glycemic control by escalating inflammation and changing the immune system’s response with an increased risk of complications, which can result in thromboembolism [15]. It is well-known that cigarette smoke causes abnormal inflammatory activation since the production of various pro-inflammatory cytokines (such as Il-6, TNF-, and KC) is increased and potentiates further morbidity and mortality [16].

It is important to note that during the COVID-19 period, cerebrovascular neurological diseases accounted for 60.2% of hospitalizations, making them the most common neurological illnesses requiring hospitalization. These findings are consistent with [17, 18] who hypothesized that individuals with COVID-19 may experience acute cerebrovascular events, including ischemic and hemorrhagic strokes and cerebral venous thrombosis. A hypercoagulable condition, cytokine storms and inflammation, endothelial dysfunction, and SARA-CoV-2 binding to endothelial ACE-2 are possible causes for the underlying processes. These disorders ultimately lead to vasoconstriction, oxidative stress, inflammation, and thrombogenesis [18]. Although cerebrovascular events were the most common among our COVID-19 patients, they were still less common than prior to the pandemic. The COVID-19 outbreak had a significant impact on cerebrovascular care, including particularly hospital care, resulting in a substantial decrease in admissions, thrombolytic therapy and interventional therapies as well as the lack of awareness combined with the terror of the virus imposed on patients with vascular disorders much less likely to request assistance. The focus on social isolation may have excessively conducted acute stroke patients to resist getting medical help in person. A patient's increased social isolation may have made it more difficult for friends and relatives to notice that they were experiencing a stroke [19].

In this study, it was surprising that the individuals with autoimmune-related diseases such as transverse myelitis and Guillain–Barré syndrome (GBS) were found to have a higher rate of hospital admissions during the pandemic era compared to before (34.2% versus 15.2%). Moreover, the confirmed COVID-19 diagnosis had the highest prevalence of autoimmune illnesses (45.5%) compared to the suspected (25.2%) cases and non-COVID (29.4%) It is significant to note that the literature may have underestimated the prevalence of this condition in COVID-19 patients since it is technically challenging to conduct an adequate neurological assessment in an intensive-care setting [20]. Several mechanisms, including both direct viral and immune-mediated pathogenicity, may play a role in the development of neurological damage associated with COVID-19. Evidence suggested the existence of immune-mediated inflammatory pathways, as demonstrated by the ongoing presence of CSF markers of inflammation [20, 21].

It has been observed that almost 60% of COVID-19 patients experienced neurological syndromes during the active infection, rather than as a post-COVID-19 infection consequence. The post-COVID-19 syndrome can lead to various neurological symptoms, including anosmia, ageusia, encephalopathy, encephalitis, myelitis, and post-infectious sequelae such as Guillain–Barré Syndrome or plexopathies [22]. COVID-19 has four stages, namely acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction [23]. Researchers have suggested that SARS-CoV-2 may remain dormant in the central nervous system of recovered individuals for an extended period, making it possible to reactivate and cause neurological disorders. Previous studies have shown that the intensity and duration of COVID-19 infection can result in various neurological complications [24]. On the contrary, recent research on COVID-19 has shown no associations with the severity of the original infection [25, 26].

Although the pandemic period witnessed a higher mortality rate compared to the pre-pandemic period, there was no noticeable difference in mortality between the durations before and after the outbreak in this study. Previous studies [27, 28] suggested that the existence of neurological conditions could predict an increased COVID-19 mortality rate, but our research findings are consistent with studies [12, 13] that showed no correlation between the increase in COVID-19 mortality and neurological disorders. According to Travi et al. (2021) [13], patients with primary neurological illnesses had a lower fatality rate, indicating that such illnesses could progress differently than respiratory syndromes. Although patients with intermediate COVID-19 severity experienced more neurological involvement compared to severe or critical patients, their increased mortality rate was likely due to respiratory deterioration rather than neurological issues. This hypothesis supports the finding that only 3 (9.1%) patients experienced severe respiratory symptoms during the pandemic era in our study, which in turn explained the lower mortality incidence observed in our study.

The COVID-19 pandemic prompted the launch of the first vaccinations in early 2021. Since then, approximately 68.2% of the global population has been fully immunized against this illness. There are four basic strategies used in producing COVID-19 vaccines: nucleic acid-based vaccines (DNA–mRNA), viral vectors (replication–non-replication), live inactivated vaccines and protein (spike protein or its subunits). After completing phase 3 clinical trials, the World Health Organization authorized 11 candidate vaccines for COVID-19 for widespread immunization in November 2021 [29]. In Egypt, the national authorities enforced the use of just five candidate vaccinations, including Sinopharm, Sinovac, AstraZeneca, Johnson, and Pfizer.

In contrast to earlier studies [30, 31], patients who did not receive immunization had a higher incidence of cerebrovascular disorders. According to a study by Marckus in 2021 [32], the occurrence of vascular adverse effects due to immunization is infrequent and less prevalent than the incidence of both cerebral venous thrombosis and ischemic stroke caused by COVID-19 infection. The increased risk of cerebrovascular disorders in COVID-19 patients is primarily due to a prothrombotic condition found in those patients, which activates the coagulation system and raises d-dimer and fibrinogen levels. This condition, known as sepsis-induced coagulopathy, is linked to infection-induced systemic inflammation [32]. There have been reports of vascular complications in the brain caused by certain COVID-19 vaccines, particularly those based on adenovirus. These complications are thought to be triggered by the immune system's response to the vaccine, which can result in thrombocytopenia and cerebral venous sinus thrombosis. It is believed that the creation of IgG antibodies against platelet factor 4 is responsible for activating platelets and causing blood clots in large venous arteries, which leads to thrombocytopenia [31].

Our study found that the most common adverse effects of COVID-19 immunization were headaches, which is consistent with findings from previous study [33]. Post-vaccination headaches can also be caused by stress and vascular spasm. Among the different types of vaccines, mRNA and adenovirus vaccines were found to be more likely to cause headaches [34]. Another common adverse effect was the exacerbation of pre-existing neurological conditions such as epilepsy. Convulsions triggered by COVID-19 vaccination can be attributed to the release of spike proteins, which cause acute inflammation and hyperthermia. As a result, hyperthermia increases glial cell activity and the permeability of the blood–brain barrier. This leads to the entry of peripheral blood cells and albumin into the brain, which alters the osmotic equilibrium [35].

During the investigation, it was found that COVID-19 vaccinations might cause immune-mediated neurological illnesses such as transverse myelitis and GBS, which have been previously reported [36, 37]. The two main mechanisms for vaccine toxicity and how these consequences emerge are ectopic immune reactivity and molecular mimicry [37]. Moreover, this study did not identify significant differences between different vaccinations despite previously reported negative effects.