Prevalence, pathogenesis and spectrum of neurological symptoms in COVID‐19 and post‐COVID‐19 syndrome: a narrative review

Abstract

Summary Neurological symptoms are not uncommon during severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and reflect a broad spectrum of neurological disorders of which clinicians should be aware. The underlying pathogenesis of neurological disease in coronavirus disease 2019 (COVID‐19) may be due to four mechanisms of nervous system dysfunction and injury: i) direct viral neurological invasion; ii) immune dysregulation; iii) endothelial dysfunction and coagulopathy; and iv) severe systemic COVID‐19 disease. Neurological manifestations of acute COVID‐19 include headache, peripheral neuropathies, seizures, encephalitis, Guillain–Barré syndrome, and cerebrovascular disease. Commonly reported long term neurological sequelae of COVID‐19 are cognitive dysfunction and dysautonomia, which despite being associated with severe acute disease are also seen in people with mild disease. Assessment of cognitive dysfunction after COVID‐19 is confounded by a high prevalence of comorbid fatigue, anxiety, and mood disorders. However, other markers of neuroaxonal breakdown suggest no significant neuronal injury apart from during severe acute COVID‐19. The long term impact of COVID‐19 on neurological diseases remains uncertain and requires ongoing vigilance.

SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system in vitro

“…There is a growing body of evidence of neurological manifestations of COVID-19, and therefore, understanding the mechanisms of SARS-CoV-2 neuropathology will have a significant impact on treatment strategies. Neurological sequelae in COVID-19 patients are diverse and include headache, encephalitis, vasculopathy and vasculitis including stroke, haemorrhage and cerebral thrombosis [20]. The underlying mechanism by which SARS-CoV-2, directly or indirectly, causes these manifestations is currently unclear, and there may be multifactorial mechanisms.…”

“…The underlying mechanism by which SARS-CoV-2, directly or indirectly, causes these manifestations is currently unclear, and there may be multifactorial mechanisms. Moreover, peripheral nervous system sequelae including Gullain-Barre syndrome, peripheral neuropathy and myopathy, likely due to severe pulmonary disease, have been reported [20,21]. Recently, medium-and long-term follow-up studies revealed an increased risk of dementia, migraine, Alzheimer's disease and other cognitive defects 12-24 months post-infection.…”

“…Supernatant was collected, aliquoted and stored at −80 °C. TCID 50 (50 % tissue culture infectious dose) was performed in VeroE6 cells in quadruplicate and infectious titre determined using the Reed-Muench method 20 . Clinical isolates representing SARS-CoV-2 variants including Alpha (CEPHR_IE_B.1.1.7_0221, GenBank accession ON350867, passage 2), Delta (CEPHR_IE_AY.50_0721, GenBank accession ON350967) and Omicron (CEPHR_IE_BA.1_0212, GenBank accession ON350968, passage 2) were isolated from SARS-CoV-2-positive nasopharyngeal swabs from the All-Ireland Infectious Disease cohort [13].…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…Patients with COVID‐19 may suffer from fever, sore throat, cough, diarrhea, sleep disorders, anxiety, depression, and cognitive impairment, which is associated with long COVID symptoms during recovery. 1 , 2 , 3 , 4 Despite some clinical trials of drugs to improve COVID‐19 symptoms, there remains no consensus on effective treatment methods, and immunocompromised elderly people and children need special attention. 5 , 6 , 7 , 8 …”