The COVID-19 pandemic has affected people from all walks of life, burdening patients, healthcare professionals, and governments in many countries [13]. Despite numerous reports of neurological deficits in patients with COVID-19 worldwide, the exact occurrence of these manifestations remains unknown. Patients with severe COVID-19 tend to have more severe neurological manifestations, possibly from cerebral hypoxia due to respiratory failure [7, 13]. We found that 6.7% of hospitalized COVID-19 patients had a serious neurologic disorder; the most common ones were ischemic stroke (54.1%), intracranial hemorrhage (18.5%), encephalopathy (8.9%), Guillain–Barre syndrome (6.4%) and MG exacerbation (3.8%).

The prevalence of neurologic manifestations in hospitalized COVID-19 patients was estimated at 36.4% in China and 57.4% in Europe [5, 7, 13, 14]. In a previous study from Iran, 4.8% (211/4372) of hospitalized COVID-19 patients had a neurological disorder; the most frequent CNS manifestations were headache (40.3%), reduced consciousness (36%), and focal neurologic symptoms (18%) [2]. In New York City, a slightly higher prevalence of 13.5% (606/4491) was reported [15]. The reported prevalence rates are heterogeneous depending on the methods and definitions for detecting neurological manifestations. For instance, the prevalence recorded in the present study (6.7%) is lower than most of the mentioned studies, probably due to our selection of serious neurological disorders requiring consultation with or admission by the neurology service.

Neurologic symptoms are sometimes the initial presentation of COVID-19 [8]; this was seen in 30% (47/157) of cases in the present study. However, most patients developed neurological manifestations after several days of onset of clinical COVID-19 symptoms. Liotta et al. reported neurologic manifestations at COVID-19 onset in 42.2%, at hospitalization in 62.7%, and at any time during the disease course in 82.3%. The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), and encephalopathy (31.8%); strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon [16]. Thirty-one percent of patients in our study had a previous history of neurological disease—mainly stroke, dementia, or myasthenia gravis. In the Herman et al. study, the rate of previous neurological illnesses varied from 0 to 40%, with a pooled percentage of 8%; cerebrovascular disease was the main comorbidity (16%), similar to our study [17]. Patients with a preceding neurological disease may be at increased risk of serious COVID-19, so special attention must be directed toward preventing COVID-19 in this population [7].

According to the current study, CNS manifestations were the most prevalent serious neurological manifestation in hospitalized COVID-19 patients, with ischemic stroke being the most common (54.1%), followed by intracranial hemorrhage (18.4%) and encephalopathy (8.9%). Overall, 72.6% of patients had cerebrovascular disease, representing the most common group of neurological disorders. Stroke was reported at 1.7% in Spain [14], 3.5% to 5.7% in China [5], and 62% in a report from the UK [18]. Studart-Neto and colleagues reported a prevalence of encephalopathy (44.4%) and stroke (16.7%) in Brazil in hospitalized COVID-19 patients requiring neurology consultations [19]. A similar study by Brucki et al. in Latin America reported stroke as the most common neurologic disorder (47.6%), followed by encephalopathy (27%) [20]. In New York City, the main neurologic disorder was toxic/metabolic encephalopathy (51%), followed by stroke (14%), seizure (12%), and hypoxic/ischemic brain injury (11%) [15]. Although our findings are generally compatible with the literature, cerebrovascular disease might have been more prevalent in our study because our center is the referral center for stroke in Ahwaz, and because the internal medicine team sometimes manages encephalopathies without a neurological consultation. Other potential factors for the difference in the prevalence and frequency of neurological manifestations include SARS-CoV-2 strain variations and genetic factors, particularly polymorphisms in the angiotensin-converting enzyme 2 (ACE 2) gene [21, 22].

Possible mechanisms behind impaired consciousness and encephalopathy include infections, parenchymal lesions, electrolyte imbalance, hypoxia, toxic and metabolic encephalopathies, and non-convulsive epilepsy [13]. One suggested explanation for the increased ischemic and vascular events in COVID-19 patients is the reduction of ACE2 by the SARS-CoV-2 virus, which may cause an imbalance of the renin-angiotensin system (RAS), eventuating in endothelial cell dysfunction and ischemic accidents. ACE2 dysregulation by SARS-CoV-2 may also lead to vasoconstriction and dysfunction of the brain, resulting in increased blood pressure, which can trigger bleeding via the rupture of arterial walls [23]. SARS-CoV-2 also ruptures existing atherosclerotic plaques via the inflammatory response involving CRP, interleukin (IL-7), interleukin 6 (IL-6), and other inflammatory markers [24]. Cardiac manifestations and arrhythmic complications of COVID-19 can also contribute to ischemic events [24], as can coagulation disorders, which have been seen in patients with severe COVID-19 [25].

The overall prevalence of peripheral nervous system manifestations was less than about 10.8% in our study. GBS was diagnosed in 6.4% of patients, with a median age of 44 (25 to 69) years. Most developed neurological symptoms several days after COVID-19. Frontera et al. reported three patients with GBS within 2–4 weeks of documented SARS-CoV-2 infection; all three had a negative RT-PCR SARS-CoV-2 in the CSF [15]. While GBS is thought to occur via postinfectious or parainfectious mechanisms, we found a rare case of GBS with a positive CSF SARS-CoV-2 PCR test in a 69-year-old woman with severe COVID-19. This rare finding, coupled with evidence of ischemia on imaging, suggests the possibility of direct CNS invasion by SARS-CoV-2, which should be explored further in future studies.

In the current study, 50 (32%) patients were in poor condition upon hospitalization, and 81 (52%) patients received invasive mechanical ventilation during hospitalization. Our in-hospital mortality rate was 44%. A definite COVID-19 diagnosis, ICU admission, previous history of stroke and dementia and associated morbidity, uremia, anemia, thrombocytopenia, leukocytosis, positive troponin, and high titers of CPK and D-dimer were associated with increased risk of mortality. In a similar study, Frontera et al. found higher in-hospital mortality rates and lower discharge rates among patients with COVID-19 with a neurologic disorder than those without a neurologic disorder. History of medical and neurologic diseases, the severity of illness (invasive mechanical ventilation and SOFA scores), and acute renal failure differences in COVID-19-specific medication administration (therapeutic anticoagulation, hydroxychloroquine, corticosteroid, lopinavir/ritonavir use) were significantly associated with in-hospital death in those with a neurologic disorder (35%) than in those without a neurologic disorder (19%) [15]. Moreover, Yaghi et al. found that patients with laboratory-confirmed COVID-19 and ischemic stroke had higher mortality rates than contemporary and historical patients with ischemic stroke who did not have COVID-19 [26]. Hence, our findings align well with the literature.

There are limitations to this study that should be highlighted. First, although our sample size was large, the study's retrospective nature resulted in many patients being lost due to a lack of requesting a neurology consultation. Second, the current study included all patients diagnosed with COVID-19 based on clinical suspicion (with and without laboratory confirmation), meaning that undocumented diagnoses or unconfirmed SARS-CoV-2 infection may lead to inaccurate estimates of the prevalence rate. Third, some patients may not have provided an accurate history of neurological symptoms due to the severity of pulmonary symptoms, which can underestimate the prevalence. Finally, in most cases, it was impossible to determine whether COVID-19 caused new neurological symptoms or worsened pre-existing ones due to insufficient information in the medical records. Well-designed prospective studies can overcome these limitations.