Long-Term Neurologic Symptoms Emerge in COVID-19

— Hospitalized patients show deficits including cognitive impairment 6 months later

MedpageToday
An illustration of a persons head surrounded by COVID-19 viruses and their brain crisscrossed with zigzagging lines

Long-term neurologic manifestations were seen in more than a third of patients hospitalized with SARS-CoV-2 infection, a prospective study in Italy showed.

In a group of hospitalized COVID-19 patients with no prior neurologic disease, 37.4% showed abnormalities on neurologic exam 6 months later -- most commonly cognitive deficits, hyposmia, and postural tremor -- according to Alessandro Padovani, MD, PhD, of the University of Brescia, and co-authors. The findings were reported in a medRxiv preprint and have not undergone peer review.

Patients also noted fatigue, memory impairment, and sleep disorders, Padovani said. "The severity of SARS-CoV-2 infection was an important predictor, together with age and premorbid condition, of long-term neurological symptoms and features in the cohort."

The findings are important for long-term management of COVID-19 patients, he told MedPage Today. "They showed that the severity of SARS-CoV-2 infection may impact on neurological sequelae, but also that the symptoms reported do not always reflect neurological features at examination."

The study is one of the first to look specifically for new long-term neurologic manifestations in COVID-19 patients who were hospitalized. Earlier research showed that 87% of patients hospitalized with COVID-19 reported persistence of at least one lingering symptom, notably fatigue and dyspnea, 60 days after discharge. Fatigue and dyspnea also were the most prevalent symptoms reported during infection and at 3-month follow-up in an analysis of both hospitalized and non-hospitalized COVID-19 patients.

Padovani and colleagues asked all COVID-19 survivors without premorbid neurologic disease who were discharged from the ASST Spedali Civili Hospital between February and April 2020 to participate in a follow-up study that included a standardized neurologic symptom checklist and a neurologic exam at 6 months.

The checklist including symptoms related to central, peripheral, myopathic, and cognitive manifestations. The exam assessed cranial nerves; motor, sensory, cerebellar, and basal ganglia-related function; deep tendon reflexes; pyramidal signs; and global cognitive function using the Montreal Cognitive Assessment (MoCA).

Premorbid conditions were recorded at hospital admission using the Cumulative Illness Rating Scale. Hospitalization data included severity of COVID-19 disease, classified according to the Brescia COVID Respiratory Severity Scale (BCRSS).

Of 165 patients, the most common symptoms reported at follow-up were fatigue (34.1%), memory complaints (30.8%), sleep disorders (30.8%), and myalgias (29.6%), followed by depression or anxiety symptoms (26.0%), blurring or other visual disturbances (19.5%), paresthesia (18.3%), and hyposmia/dysgeusia (16.5%).

In addition, 14.0% of patients reported urinary dysfunction, 13.0% confusion/dizziness, 12.2% dizziness/hypotension, 10.7% gait disturbances, and 8.5% postural instability or falls.

Patients with worse BCRSS scores reported a higher number of symptoms at follow-up (P=0.004), memory complaints (P=0.015), and visual disturbances (P=0.006), after adjusting for age and premorbid conditions. Age (P=0.028) and oxygen therapy (P=0.04) best predicted memory complaints.

A total of 105 patients were evaluated further by neurologic exam and cognitive screening. Of these, 42 people showed neurologic abnormalities: 19 had hyposmia/dysgeusia, 15 had enhanced physiological tremor, six had low-limb hypoesthesia, three had low-limb motor deficits, and 17 had cognitive deficits according to MoCA Italian validated norms. None of these patients had a history of cognitive impairment, Padovani noted.

Neurologic abnormalities seen on exam were associated with older age (P=0.005), higher premorbid comorbidity index (P=0.001), worse BCRSS scores (P=0.05), longer hospitalization duration (P=0.002), and higher number of neurologic symptoms reported (P=0.007). Length of hospitalization (P=0.02) and premorbid comorbidity index (P=0.03) predicted neurologic abnormalities.

Cognitive impairment was specifically associated with severity of COVID-19, independently of age and pre-morbid conditions. "On one hand, this suggests that hospitalization and severity of COVID-19 have a large impact in subjects with increased multi-morbidity, in line with other infectious diseases, such as community-acquired pneumonia," the researchers noted.

On the other hand, the persistence of cognitive deficits "needs to be addressed in COVID-19 follow-up programs to evaluate their impact and progression over time and disentangle their potential relationship with psychosocial and psychiatric disturbances," the investigators pointed out.

To that end, a global prospective study to investigate links between COVID-19 and cognitive decline was announced this week by the Alzheimer's Association, the World Health Organization, and others.

The research had several limitations, the team said. It was a single-center study with a relatively small sample size; premorbid conditions were based on medical records and assessment during hospitalization without extensive neurologic screening at baseline; and patients who developed neurologic disease during the acute phase of SARS-CoV-2 infection were not included.

  • Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

The study received no funding.

The researchers reported relationships with GE Healthcare, Eli Lilly, Actelion Ltd Pharmaceuticals, Nutricia, PIAM, Langstone Technology, UCB, Chiesi Pharmaceuticals, Biomarin, Zambon, AbbVie, and Vitaflo Germany.

Primary Source

medRxiv

Source Reference: Pilotto A, et al "COVID-19 severity impacts on long-term neurological manifestation after hospitalization" medRxiv 2021; DOI: 10.1101/2020.12.27.20248903.