Does Age Predict Severity of Neurologic Manifestations of “Long COVID?”

Younger and middle-aged individuals (18-64 years) are likely to be severely affected by neurologic manifestations of postacute sequelae of SARS-CoV-2 infection (Neuro-PASC), according to study findings published in Annals of Neurology.

Previous studies have shown varying results regarding the association between age and PASC, with limited information available on the effect of Neuro-PASC on individuals in different age groups.

Therefore, researchers determined the severity of neurologic manifestations of PASC across the adult lifespan to inform future risk stratification and resource allocation for the long-term care of this patient population.

Eligible participants who tested positive for SARS-CoV-2 infection and reported any associated neurologic symptoms for at least 6 weeks after COVID-19 onset were included in the analysis. Neuro-PASC was defined as a symptom duration of 4 weeks or longer after COVID-19 onset. Patients were categorized into 3 groups based on age: younger (18-44 years), middle-aged (45-64 years), and older (65+ years).

Between May 2020 and March 2023, the researchers collected data from participants using questionnaires based on the patient-reported outcomes measurement information system (PROMIS), such as measures for quality of life domains (cognition, fatigue, sleep disturbances, and depression). In addition, all participants underwent a complete neurologic exam at the clinic.

A total of 1300 patients were included in the study, with 200 (mean age, 55.6 years) having posthospitalization Neuro-PASC (PNP) and the remaining 1100 (mean age, 46.2 years) having nonhospitalized Neuro-PASC (NNP). The majority of the PNP group included middle-aged patients and the NNP group included younger patients. Together, the majority of the PNP and NNP groups included younger and middle-aged individuals, respectively (71.0% and 90.5%, respectively).

The researchers observed age-related differences in frequency of neurologic symptoms, including headache, numbness/tingling, dysgeusia, and anosmia, in the NNP group, and blurred vision in the PNP group — the older group had a lower prevalence of neurologic symptoms. Non-neurologic symptoms, such as depression/anxiety, in the NNP group, and insomnia in the PNP group, also had a lower frequency among older individuals. Overall, both neurologic and non-neurologic symptoms were lower among older adults with Neuro-PASC.

Significant age-related differences were noted in patient-reported symptoms of fatigue and sleep disturbances in the NNP group (P =.04 and P =.002), with a reduced quality of life among younger participants. Researchers also noted age-related differences in objective executive function (P =.01) in both the PNP and NNP groups, and working memory (P =.0002) in the NNP group, with worse performances among younger individuals. Overall, older vs younger participants had lesser impairments in quality of life and cognitive performance.

Limitations of the analysis were differing definitions of PASC with regarding to duration of symptoms; selection bias, as all patients were enrolled from a single center; and lack of a control group without COVID-19 and cognitive and quality of life impairments.

“These findings have [an] immense public health impact given that Neuro-PASC significantly contributes to the leading global burden of disability and disease caused by neurologic disorders,” the researchers concluded.