April 2023

NEUROSCIENCES

NEUROLOGIC MANIFESTATIONS OF LONG COVID-19 DIFFER BASED ON ACUTE COVID-19 SEVERITY

Patients previously hospitalized for COVID-19 pneumonia showed broad cognitive impairment, while those with mild initial infection that did not require hospitalization mainly had difficulties with attention tasks

​A Northwestern Medicine study published in Annals of Neurology shows neurological symptoms, findings and patterns of cognitive dysfunction differ between long COVID-19 patients who were hospitalized during their acute infection and those who didn’t require hospitalization. Researchers studied the first 600 patients with long COVID-19 who were evaluated at the Northwestern Medicine Neuro COVID-19 Clinic. They found that those initially hospitalized for acute COVID-19 pneumonia showed a broad pattern of cognitive impairment and lack of insight into their cognitive dysfunction. Meanwhile, non-hospitalized patients with long COVID-19 mainly had difficulties with attention tasks.
 
“We were surprised to find that even though both post-hospitalization and non-hospitalized long-haulers report brain fog, there were marked differences in their pattern of cognitive dysfunction, which suggests distinct causes and mechanisms of long COVID in these populations,” says Igor J. Koralnik, MD, chief of Neuro-infectious Diseases and Global Neurology at Northwestern Medicine. He oversees the Neuro COVID-19 Clinic and is co-director of the Northwestern Medicine Comprehensive COVID-19 Center.
 
This study focused on the first 600 patients (100 post-hospitalization, 500 non-hospitalized) who had a documented COVID-19 infection and came to the Neuro COVID-19 Clinic either in person or via telemedicine between May 2020 and August 2021. These patients reported an average of seven neurologic symptoms due to COVID-19, with 91% experiencing more than four neurological symptoms.
 
Neurologic Symptoms
  • 81% experienced brain fog
  • 70% experienced headaches
  • 56% lost their sense of smell
  • 55% had an altered sense of taste
  • 50% experienced dizziness
Hospitalized patients had more abnormal neurologic exams (62% vs 37%) and performed worse on processing speed, attention and working memory tasks. Non-hospitalized patients had lower results in attention tasks only.
 
Non-neurologic Symptoms
  • 86% experienced fatigue
  • 69% experienced depression/anxiety
  • 57% had insomnia
  • 48% experienced shortness of breath
  • 34% self-reported variation of heart rate and blood pressure
  • 30% experienced chest pain
  • 27% had gastrointestinal symptoms such as nausea, vomiting or diarrhea
Of these symptoms, only shortness of breath and chest pain were significantly more frequent in the post-hospitalization group than non-hospitalized.
 
Demographics and Comorbidities
Both groups demonstrated a significantly different quality of life in cognition, fatigue, sleep, anxiety and depression compared to the U.S. normative population, but have significant differences in demographics and comorbidities.
 
Of the 100 post-hospitalization patients:
  • Average age was 54
  • 58% were female
  • 62% were white, 18% were Black, 3% were Asian and 19% were Hispanic
  • Compared with patients who weren’t hospitalized, this group had:
    • Hypertension more frequently (39% vs 15%)
    • High cholesterol more frequently (22% vs 13%)
    • Type 2 diabetes more frequently (21% vs 4%)
    • Lung diseases more frequently(16% vs 4%)
    • Cardiovascular diseases more frequently (10% vs 2%)
Of the 500 non-hospitalized patients:
  • Average age was 45
  • 66% were female
  • 77% were white, 8% were Black, 4% were Asian and 12% were Hispanic  
  • Non-hospitalized patients were more likely than post-hospitalization patients to suffer from depression/anxiety prior to COVID-19 (40% vs 9%)
The demographic, comorbidities, and clinical and cognitive differences highlighted in the study suggest distinct etiologies of long COVID-19 in hospitalized and non-hospitalized patients, warranting targeted interventions.
 
“For patients previously hospitalized with COVID-19, it’s possible they suffered diffuse brain damage, which could have been caused by a combination of hypoxemia, cytokine storm, multi-organ failure, or encephalopathy which may not be visible on brain CT or MRI. This is consistent with the broad cognitive dysfunction harbored by these patients,” says Dr Koralnik. “Conversely, the female predominance of non-hospitalized patients suggests an autoimmune etiology of long COVID in this population, perhaps triggered by viral persistence. Indeed, women are more likely than men to develop autoimmune diseases.”
 
Of the 600 patients involved in the study, 43% were vaccinated and all but one patient became infected before vaccination. At the time of their clinic visit, patients felt approximately 60% recovered back to their pre-COVID-19 baseline.
 
Northwestern Medicine scientists plan to continue studying long COVID-19 over the adult lifespan, comparing patients in these age groups: 18 to 44 years old, 45 to 64 years old, and older than 65 years. This will help determine if there are differences between those groups and if either group was more affected at a specific time by different circulating strains.
 
“Long COVID occurs in approximately a third of COVID-19 survivors and is now the third leading neurologic disorder in the United States. Long COVID has a significant detrimental effect in patients’ quality of life and has pushed an estimated one million people out of work in the U.S.,” says Dr. Koralnik. “Considering the large number of people impacted by long COVID and the continuing potential for infection leading to persistent and potentially disabling neurological symptoms, there should be a greater emphasis on funding research on the root causes of long COVID, leading to clinical trials in the U.S.”
 
As of April 2023, the Neuro COVID-19 Clinic has treated nearly 2,000 patients with long COVID-19. For more information, visit nm.org and refer a patient, please call 312.695.7950 (TTY: 711).

This article was originally published in the Northwestern Medicine Newsroom on April 19, 2023. 
Igor Koralnik, MD is the Chief of Neuro-infectious Disease and Global Neurology in the Department of Neurology at Northwestern Medicine. 

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