As more COVID-19 research emerges, more data suggests that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) damages the central nervous system. Brain fog and memory problems are two of the most reported neurological complications for people with long COVID. However, the long-term neurological effects after recovering from COVID-19 infection remain under investigation.
Results from a recent observational study published in the Journal Of The Neurological Sciences found that after a 4-month follow-up, ICU patients with severe COVID-19 illness were more likely to have mild cognitive impairment with features related to a diffuse encephalopathy than patients with mild infection who do not need a ventilator. Additionally, ICU patients experienced more significant impairment in executive function. All neurological deficits involve the peripheral nervous system.
The study took place at the University Hospital of Brescia, where they enrolled 215 adult patients who were previously infected with symptomatic COVID-19 illness. A total of 163 patients had a mild or moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and did not require oxygen support. However, about 52 were diagnosed with a severe or critical infection that required ICU admission.
ICU patients were older and were more likely to have a lower education level. They also had secondary complications, such as diabetes and hypertension. Although, having obesity or preexisting respiratory diseases did not seem to make a difference with ICU admission rates.
Non-ICU patients had mild to moderate infections. All had respiratory symptoms, and 10% of patients had a positive chest X-ray for interstitial pneumonia. Among patients who reported their treatment history, 16.7% were given hydroxychloroquine and 5% with steroids. Home treatments involved varying ranges of antibiotics and anti-inflammatory drugs.
ICU patients had severe or critical COVID-19 illnesses. Eighty-two percent had acute respiratory distress syndrome. All ICU patients required oxygen. Patients stayed in the ICU for an average of 15 days.
Treatment for ICU patients consisted of enoxaparin and antibiotic therapy. In addition, Tocilizumab was given to one patient, and steroids were used in 16 cases for almost six days. About 36% of ICU patients required a tracheostomy, and 15% had been pronated to some extent.
Two patients were diagnosed with Guillain-Barre syndrome during their ICU stay, and 13% had a pulmonary embolism. There was no evidence of stroke or encephalitis.
How they did it
The researchers conducted a follow-up neurological exam and neuropsychological evaluation four months after diagnosis. The neuropsychological test is used to study people with brain diseases. It was added to a test of general cognition called the MMSE to better evaluate mild and specific changes in cognitive abilities.
A separate assessment tested verbal and nonverbal memory, visuospatial and executive function, as well as verbal fluency by semantic and phonemic cues.
ICU patients were evaluated at an average of 141 days after diagnosis, while non-ICU patients were given a follow-up at a mean of 121 days.
Neurological outcomes after a 4-month follow-up
With the exception of two patients who presented with limb areflexia and sensory loss with radicular distribution from a preexisting lumbar disc herniation, all non-ICU patients had no neurological complications 4 months after their COVID-19 diagnosis.
In contrast, seven patients who were hospitalized in the ICU had neurological deficits during follow-up. About 7% had decreased tendon reflexes in both legs, 1.9% had reduced tactile sensation in the thigh, 1% showed signs of a tremor, and another 1% had hypoesthesia and areflexia in the left arm without sensory deficits.
Peripheral neuropathy was observed in the first 4 ICU cases.
MMSE results showed that ICU patients were more likely to have mild cognitive impairments than non-ICU patients. They also had lower scores on all the neuropsychological tests.
An ICU patient’s old age and lower level of education were associated with more severe cognitive impairment.
Study limitations and future directions
A study limitation was the uneven sample sizes between groups. There were more non-ICU than ICU patients enrolled in the research study.
Moreover, the study did not conduct brain imaging and immunological and CSF analyses. Conducting these tests would have provided greater insight into the pathophysiological mechanisms underlying neurological complications.
Future studies should focus on recruiting participants who recovered from COVID-19 infection. Doing so would allow researchers to study the duration of neurological complications as well as investigate the origin of cognitive deficits during and after infection. In addition, a collaborative study involving critical care specialists and experts on post-intensive care syndrome would help to understand the causes behind neurological long COVID symptoms comprehensively.