Neurological sequelae of COVID-19 infection


A number of recent studies have reported on the incidence of acute neurological complications of COVID-19 infection, as well as long-term complications, variously called PASC (post-acute sequelae of COVID-19) or ‘long COVID’. Data were reported at the American Academy of Neurology annual meeting, held April 2-7 in Seattle, Washington.

An analysis of the Society of Critical Care Medicine’s multinational Viral Infection and Respiratory Illness University Study (VIRUS) database of confirmed COVID-19 infections (N=16,225) reported that 12.9% had serious neurological symptoms (Cervantes-Arslanian et al. AAN 2022; S18.001). Complications included encephalopathy (10.2%), stroke (2.0%), seizure (1.5%) and meningitis/encephalitis (0.5%). Median age was 72 years. Neurological complications were more common in patients with severe COVID-19 (odds ratio 1.82) and were associated with higher 28-day mortality (OR 1.58).

Similar data were reported by a group at Rutgers (Gad et al. AAN 2022; S18.010). Overall, 25.3% of COVID-19 patients developed neurological complications. The mortality rate was three-fold higher than in COVID patients without neurological complications. ICU length of stay was longer in COVID patients with neurological complications versus non-COVID patients with neurological complications (11 vs. 5 days).

A systematic review found that the most commonly reported neurological complications were acute ischemic cerebrovascular accident and Guillain–Barré syndrome; meningitis and/or encephalitis were least commonly reported (Naik et al. AAN 2022; P9.001). Neurological syndromes were more common in patients with pre-existing neurological disorders.


An emerging topic in the medical and cultural spheres is long-term complications of COVID-19. At present, ‘long COVID’ is a poorly-defined syndrome that comprises various neurologic and psychiatric symptoms occurring >3 months after acute infection.

A meta-analysis of 19 studies (N=11,324) reported a high prevalence rate for fatigue (37%), brain fog (32%), memory issues (27%), attention disorder (22%), myalgia (18%), anosmia (12%), dysgeusia (11%) and headache (10%) (Premraj et al. AAN 2022; N6.001). Psychiatric symptoms included sleep disturbance (31%), anxiety (23%) and depression (12%). Hospital admission for COVID-19 was associated with an increased risk of memory problems (OR 1.9). However, hospitalized patients had a lower likelihood of reporting long COVID symptoms such as anxiety, depression, fatigue, headache, myalgia and sleep disturbance.

In the ALBERTA HOPE COVID-19 trial (median age 45 years), 14.1% of subjects had a pre-existing neurological or psychiatric disorder (Ganesh et al. AAN 2022). At one year post-infection, 22.3% reported persistent symptoms such as headache (52.5%), confusion (50%), insomnia (40%) and depression (35%). Factors associated with persistent symptoms included female sex (OR 5.04), higher BMI, prior neurological/psychiatric history, asthma, and lack of full-time employment. A total of 42.9% had cognitive impairment (telephone MOCA score <18 out of 22) at one year.

A U.S. study reported on 93 patients (mean age 50 years) presenting with PASC a median of nine months post-infection (Thawani et al. AAN 2022; S18.005). The most common symptoms were fatigue (67%), headache (49%), muscle ache (48%), word-finding difficulty (48%), difficulty sleeping (47%), dyspnea (47%), and change in memory (46%). Premorbid conditions included anxiety/depression (32%), hypertension (26%), pulmonary disease (23%) and autoimmunity (17%). In this group, 68% had BMI >25 and 41% had a prior neurological condition (e.g. migraine, 18%). Patients reporting persistent fatigue had mean Neuro-QOL fatigue scores within the normal range. Those reporting difficulties with memory or word finding had normal MOCA scores, which was interpreted as an indication that MOCA may not detect subtle cognitive deficits in this population.

Similarly, a retrospective study reported that 91% of patients (mean age 50 years) reported some degree of brain fog (Schindler et al. AAN 2022; S18.009). A minority of subjects had some degree of cognitive impairment on MOCA (39%) or Trails B (16%). The authors suggested that the discrepancy between patient reports of cognitive impairment and objective testing may indicate that brain fog may be attributable to multiple factors.

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