Neurological symptoms, findings, and patterns of cognitive dysfunction differ between long COVID patients who were hospitalized during their acute infection and those who didn’t require hospitalization, according to new research published in Annals of Neurology.

Researchers studied the first 600 long-haulers who were evaluated at the Northwestern Medicine Neuro COVID-19 Clinic and discovered those initially hospitalized for acute COVID-19 pneumonia showed a broad pattern of cognitive impairment and lack of insight into their cognitive dysfunction, while non-hospitalized long-haulers 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,” said Igor Koralnik, MD, chief of neuroinfectious diseases and global neurology at Northwestern Medicine, who oversees the Neuro COVID-19 Clinic and is co-director of the Northwestern Medicine Comprehensive COVID-19 Center.

Researchers focused this study 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 to August 2021. 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 significant altered quality of life in domains of 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% Black, 3% Asian, and 19% Hispanic
  • Post-hospitalization patients more frequently than non-hospitalized had hypertension (39% vs 15%), high cholesterol (22% vs 13%), type II diabetes (21% vs 4%), lung diseases (16% vs 4%) and cardiovascular diseases (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, clinical and cognitive differences highlighted in the study suggest distinct etiologies of long COVID 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,” said 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 baseline.

Northwestern Medicine researchers plan to continue studying long COVID over the adult lifespan, comparing patients 18-44 years old, 45-64 years old, and over 65 years old to determine if there are differences between those groups and if either group was more affected at a specific time of the pandemic 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.,” said 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.”