Frequency, Persistence, and Patient-reported Outcomes of Neurological Symptomsin Mild COVID-19: Resultsfrom the ALBERTA HOPE COVID-19 Trial

ABSTRACT

Objective: To examine the natural history of neurological symptoms in mild COVID-19. Background: Various neurological manifestations have been reported with COVID-19, mostly in retrospective studies of hospitalized patients. There are few data on patients with mild COVID19. Design/Methods: Consenting participants in the ALBERTA HOPE COVID-19 trial( NCT04329611, hydroxychloroquine vs placebo for 5-days), managed as outpatients, were prospectively assessed 3-months and 1-year after their positive test. They completed detailed neurological symptom questionnaires, Telephone Montreal Cognitive Assessment(T-MoCA), Kessler Psychological Distress Scale(K10), and the EQ-5D-3L(quality-of-life). Informants completed the Mild Behavioural Impairment Checklist(MBI-C) and Informant Questionnaire on Cognitive Decline(IQCODE). We tracked healthcare utilization and neurological investigations using medical records. Results: Among 198 patients (median age45, IQR37-54, 43.9% female);28(14.1%) had preexisting neurological/psychiatric disorders. Among 179 patients with symptom assessments, 139(77.7%) reported ≥1 neurological symptom, the most common being anosmia/dysgeusia(56.3%), myalgia(42.6%), and headache(41.8%). Symptoms generally began within 1-week of illness(median6-days, IQR4-8). Most resolved after 3-months;40 patients(22.3%) reported persistent symptoms at 1-year, with 27(15.1%) reporting no improvement. Persistent symptoms included confusion(50%), headache(52.5%), insomnia(40%), and depression(35%). Body mass index, prior neurologic/psychiatric history, asthma, and lack of full-time employment were associated with presence and persistence of neurological symptoms;only female sex was independently associated on multivariable logistic regression(aOR5.04, 95%CI1.58-16.1). Patients with persistent symptoms had more hospitalizations and family physician visits, worse MBI-C scores, and were less often independent for instrumental daily activities at 1-year(77.8% vs 98.2%, p=0.005). Patients with any or persistent neurological symptoms had greater psychological distress defined as K10≥20(aOR21.0, 95%CI1.96-225) and worse quality-of-life ratings(mean EQ-5D VAS67.0 vs 82.8, p=0.0002). 50.0% of patients had T-MoCA<18 at 3-months versus 42.9% at 1-year;patients reporting memory complaints were more likely to have informant-reported cognitive-behavioural decline (aOR[1-year IQCODE>3.3]12.7, 95%CI1.08-150). Conclusions: Neurological symptoms were commonly reported in survivors of mild COVID-19 and persisted in one in five patients 1-year later. These symptoms were associated with worse patient-reported outcomes.