Researchers explore neurological manifestations among long COVID patients

In a recent study published in natural medicineresearchers assessed long-term neurological sequelae in the post-acute phase of coronavirus disease 2019 (COVID-19) or long COVD.

Study: Long-term neurological outcomes of COVID-19. Image Credit: Starocean/Shutterstock

Long COVID refers to the spectrum of post-acute sequelae of COVID-19 involving several extrapulmonary manifestations, including neurological abnormalities. Most studies of long-term neurological impairment associated with COVID have been limited to patients hospitalized with acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infections, followed for <6 months for a small range of neurological findings.

A comprehensive evaluation of long COVID neurological outcomes after one year of acute COVID-19 is needed, assessing neurological outcomes in different care settings during the acute phase of COVID-19, including those who were out-of-hospital, hospitalized and in an intensive care unit (ICU -admitted).

About the study

In the current study, researchers assessed neurological sequelae in long-term COVID patients.

Data were obtained from United States Department of Veterans Affairs (US) national health care databases for 154,068 people who lived beyond the initial month of SARS infections -CoV-2 and two control groups of people: the contemporary control group comprising 5,638,795 US HAVs (veterans’ health system department) users not exposed to SARS-CoV-2, and the historical control group comprising 5,859,621 US HAV users prior to the SARS-CoV-2 pandemic (2017).

Inverse probability weighting was used to balance COVID-19 and contemporaneous control groups, hazard ratios (HRs) were calculated, and burdens and risks of predefined neurological disorders after one year of acute COVID-19 were been estimated. In addition, the team assessed incident neurological disorders among the SARS-CoV-2 infection group based on COVID-19 acute care settings (inpatient, inpatient, and intensive care unit admissions comprising 131,915, 16 764 and 5389 patients, respectively).

In addition, two sensitivity analyzes were performed; one involved only predefined covariates, and the other involved applying covariate adjustments and weights. To verify the reproducibility of the study approach, fatigue was assessed as a control for positive outcome and receipt of influenza vaccinations between March 1, 2020 and January 15, 2021, odd and even calendar days in 571,291 and 605,453 people, respectively, as negative exposure controls.


Individuals who lived beyond the initial month of SARS-CoV-2 infections showed a high risk of developing cerebral venous thrombosis (CVT, HR 2.7; burden 0.1), hemorrhagic stroke ( HR 2.2; load 0.2) and ischemic stroke [HR 1.5; burden 3.4 for every 1,000 individuals at one-year, transient ischemic attacks (HR 1.6; burden 2.0)]. The burden and risk of the composite cerebrovascular outcome were 4.9 and 1.6, respectively.

High risks were noted for Alzheimer’s disease (AD, RR 2.0, burden 1.7) and memory problems (RR 1.8; burden 10) with composite burden and risk for memory and cognition of 10 and 1.8, respectively. The risks and burdens of peripheral neuropathic disease (HR 1.3, burden 5.6), paresthesia (HR 1.3, burden 2.9), Bell’s palsy (HR 1.5, burden 0 .3) and dysautonomia (HR 1.3, burden 1.6) with the outcome of peripheral nerve disorder the composite burden and risk being 8.6 and 1.3, respectively.

Outcomes for episodic disorders included seizures and epilepsy (HR 1.8; burden 2.0), headache-related illnesses (HR 1.4, burden 1.5), and migraine (HR 1.2 , burden 2.0), with the combined burden and risk for the episodic disorder outcome being 4.8. and 1.3, respectively. Movement and extrapyramidal disorders included involuntary movement abnormalities (HR 1.4, burden 2.9), tremor (HR 1.4, burden 1.1), Parkinson-like disease (HR 1.5, burden 0.9), myoclonus (HR 1.4, burden 0.1) and dystonia (HR 1.4, burden 0.1). 1.6, burden 0.4) with the composite burden and risk for the outcome of movement and extrapyramidal disorder being 4.0 and 1.4, respectively.

Mental illnesses included major depressive illnesses (HR 1.4, burden 17), adaptation and stress illnesses (HR 1.4, burden 14.3), anxiety (HR 1.4, burden 12, 4) and psychotic illnesses (HR 1.5, burden 1.0). The composite burden and risk of mental health problems were 25 and 1.4, respectively. Musculoskeletal diseases included arthralgia (HR 1.3, burden 28), myopathic disease (HR 2.8, burden 0.7) and myalgia (HR 1.8, burden 16), burden and composite risk of musculoskeletal disorders being respectively 40 and 1.5.

Sensory disturbance outcomes included tinnitus or hearing abnormalities (HR 1.2, burden 11.9), vision dysfunction (HR 1.3, burden 5.6), loss of smell (HR 4 .1, burden 1.1) and loss of taste (HR 2.3, burden 0.1), with the composite burden and risk of sensory impairment being 17 and 1.3, respectively. Other findings of neurological or associated disorders included somnolence (HR 1.7, burden 0.6), dizziness (HR 1.4, burden 6.7), Guillain-Barré syndrome (HR 2.2, burden 0.1), transverse myelitis (HR 1.5, burden 0.03) and encephalopathy or encephalitis (HR 1.8, burden 0.1) and the composite burden and risk for the other neurological or associated disorder score were 7.4 and 1.5, respectively.

The overall burden and risk of any predefined neurological sequelae were estimated to be 71 and 1.4 per 1,000 people at one year after acute COVID-19, respectively, compared to contemporary controls. Risks and burdens among COVID-19 patients (compared to contemporary controls) were elevated even among patients not requiring hospitalization for acute COVID-19, depending on the severity of COVID-19.

The risks of developing episodic disorders, mental health disorders, musculoskeletal disorders and any neurological disorders increased with age. On the other hand, those of cognitive and memory disorders, sensory disorders and other neurological or associated disorders decrease with age. Similar results were obtained in sensitivity analyses, and COVID-19 was associated with elevated fatigue risks compared to contemporary controls, but had no significant association with influenza vaccinations.

Overall, the study results highlighted the neurological sequelae of long COVID, which would help guide policy-making and health care planning for long COVID patient care.

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