Long COVID Neurologic Symptoms Vary Based on Severity of Initial Infection

Two groups of long COVID patients — those hospitalized for acute COVID, and those with mild SARS-CoV-2 infection who weren’t hospitalized — had different neurologic manifestations, prospective data showed.

Long COVID patients who were hospitalized with acute infection more frequently had an abnormal neurologic exam (62% vs 37%, P<0.0001) and performed worse on processing speed, attention, and working memory tasks than patients who weren’t hospitalized, according to Igor Koralnik, MD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues.

Those with mild infection who weren’t hospitalized had brain fog (81%), headache (70%), anosmia (56%), dysgeusia (55%), and dizziness (50%) as their main neurologic long COVID symptoms, the researchers reported in Annals of Neurology. Their cognitive tests showed lower results only in attention tasks, compared with a U.S. normative population.

Neither the CDC, WHO, nor NIH definitions of long COVID (also called post-acute sequelae of SARS-CoV-2 infection, or PASC) differentiate patients based on acute symptom severity, Koralnik and co-authors observed. Differences between hospitalized and non-hospitalized patients in this study “suggest that distinct pathogenic mechanisms may be at play in those two groups, emphasizing the need to evaluate these populations separately,” they wrote.

Understanding similarities and differences between these two groups is important, noted Ziyad Al-Aly, MD, chief of research and development at the VA St. Louis Health Care System and a clinical epidemiologist at Washington University in St. Louis, who wasn’t involved with the study.

“It can deepen our understanding of the mechanisms of these sequelae — how and why they come about — and their clinical presentation, potentially informing strategies to optimize the care needs of each group,” Al-Aly told MedPage Today.

How COVID may affect the brain is a complex question that’s still largely unanswered. Hospitalized COVID patients have shown elevated levels of brain injury biomarkers, and autopsies demonstrated that SARS-CoV-2 can persist in the brain but with little evidence of inflammation or direct viral cytopathology. Even among people with mild COVID, reports of tissue damage and loss of gray matter volume have emerged.

At the Northwestern Memorial Hospital Neuro COVID-19 Clinic, Koralnik and colleagues evaluated the first 100 consecutive long COVID patients who had been hospitalized with acute infection and 500 patients who had not been hospitalized between May 2020 and August 2021.

Patients were included if they had clinical manifestations of COVID-19 confirmed by positive reverse transcription polymerase chain reaction (RT-PCR), a rapid antigen positive test of a nasopharyngeal swab, or positive SARS-CoV-2 antibody testing prior to COVID-19 vaccination. All participants had persistent neurologic symptoms for at least 6 weeks from onset.

The researchers used the NIH Toolbox to measure cognitive function. Patient-reported quality of life was evaluated with the Patient-Reported Outcomes Measurement Information System (PROMIS). Results were expressed as T scores and compared with a U.S. reference population.

The mean age of long COVID patients who had been hospitalized was 54, and 58% were women; 62% were white, 19% were Hispanic, 18% were Black, and 3% were Asian. The mean age of the non-hospitalized group was 45, and 66% were women; 77% were white, 12% were Hispanic, 8% were Black, and 4% were Asian.

Overall, 43% were vaccinated and all but one patient became infected before vaccination. Compared with the non-hospitalized group, hospitalized patients more frequently had hypertension (39% vs 15%), dyslipidemia (22% vs 13%), type 2 diabetes (21% vs 4%), lung disease (16% vs 4%), or cardiovascular disease (10% vs 2%). Non-hospitalized patients were more likely to have depression or anxiety prior to COVID-19 (40% vs 9%).

Patients were evaluated 6.8 months after symptom onset on average. Subjective impression of recovery compared with pre-COVID baseline was about 60% overall, with no significant difference between the hospitalized and non-hospitalized groups.

Both groups reported significantly altered quality of life in cognition, fatigue, sleep, anxiety, and depression compared with the U.S. normative population. Median T scores indicated moderate impairment, with no significant difference between the hospitalized and non-hospitalized groups.

The study had several limitations, Koralnik and co-authors acknowledged. The sample was based on self-selected people who sought care at the clinic without physician referral. About half of patients in each group came from televisits. In addition, the study did not have contemporaneous control groups and relied on normative population data for some comparisons.