COVID-19
Neurological symptoms have been sporadically reported in COVID-19 patients but have not yet been well studied [48,49]. The current body of evidence suggests that the SARS-CoV-2 can affect the nervous system in previously unsuspected ways [50]. The neuroinvasive capabilities of the SARS-CoV-2 doubtless exist but remain to be elucidated. Observed neurological symptoms of COVID-19 include febrile seizures, convulsions, mental status changes, and encephalitis [51]. Among the most commonly reported possibly neurological symptoms of COVID-19 are nonspecific symptoms, such as headache, myalgia, dizziness, and fatigue [21]. In a study at a single center in China (n = 214), 36.4% (n = 78) of hospitalized COVID-19 patients had what were identified as neurological symptoms[52]. In a multicenter retrospective study from Europe of 417 patients who recovered from mild to moderate COVID-19, 86% reported olfactory dysfunction and 88% problems with taste. In fact, in 12% of patients, the loss of the sense of smell was the first symptom of COVID-19 [53]. The loss of smell has emerged as being more prevalent among patients infected with COVID-19 than patients infected with other viruses or with other types of respiratory conditions [54] and has been recommended as a symptom that may help guide earlier diagnosis and treatment of COVID-19 [55]. In a meta-analysis (n = 1,627 patients, 10 studies), a loss of the sense of smell was reported in 53% of COVID-19 patients [55].
It appears that the frequency of neurological symptoms is associated with COVID-19 disease severity. In the aforementioned study of 214 hospitalized patients with COVID-19 infection (41% severe and 59% non-severe disease), severe patients were more likely than non-severe patients to have neurologically related manifestations (45.5% vs. 30.2%, respectively). In this study, the most frequently reported neurological manifestations for severe and non-severe patients, respectively, were acute cerebrovascular disease (5.7% vs. 0.8%), impaired consciousness (14.8% vs. 2.4%) and skeletal muscle injury (19.3% vs. 4.8%) [52]. This does not take into account more diffuse symptoms, such as confusion or headache, which may also be neurological [51].
Most COVID-19 patients seem to exhibit pulmonary symptoms before neurological ones [49]. About a third of diagnosed COVID-19 patients have some form of symptomology of suspected neurological origin, which might include headache, dizziness, impaired consciousness, ataxia, epilepsy, and cerebrovascular disease [49]. Besides an impaired or absent sense of smell or taste, vision disturbances, neuralgia, and skeletal muscle damage have also been reported [49]. Nucleic acid from the SARS-CoV-2 virus has been detected in the cerebrospinal fluid of patients, and the virus itself has been identified in brain tissue on autopsy of patients who died of COVID-19 [49]. Such findings are rare but confirm that the SARS-CoV-2 virus can enter the CNS. A 24-year-old Japanese man with COVID-19 presented with generalized epileptic seizures and decreased consciousness; RNA from the SARS-CoV-2 was not detectable in his nasopharynx but was identified in the cerebrospinal fluid [56]. Using a polymerase chain reaction (PCR) assay, the SARS-CoV-2 was likewise detected in the cerebrospinal fluid of an obese 40-year-old female COVID-19 patient with diabetes [57].