Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19

Abstract

Background/Objectives:Little is known about trajectories of recovery 12-months after hospitalization for severe COVID.Methods:We conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test.Results:Twelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel<100 (64%), t-MoCA≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%) and poor sleep (10%). 12-month mRS scores did not differ significantly among those with (N=113) or without (N=129) neurological complications during hospitalization after adjusting for age, sex, race, pre-COVID mRS and intubation status (adjusted OR 1.4, 95% CI0.8-2.5), though those with neurological complications had higher fatigue scores (T-score 47 vs 44, P=0.037). Significant improvements in outcome trajectories from 6- to 12-months were observed in t-MoCA scores (56% improved, median difference 1 point, P=0.002), and Neuro-QoL anxiety scores (45% improved, P=0.003). Non-significant improvements occurred in fatigue, sleep and depression scores in 48%, 48% and 38% of patients, respectively. Barthel and mRS scores remained unchanged between 6 and 12-months in >50% of patients.Discussion:At 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.

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“…This also means that most impaired patients at the 2-month visit performed in the impaired range across the study timeline representing persistent CI. This contrasts against studies which have focused on severe cases of acute COVID-19 where pre-morbid neurological conditions predict cognitive deterioration 3 . Our finding of cognitive decline/failure to improve is in accordance with emerging cognitive 3,48 and brain imaging 49 studies assessing post-acute mild-moderate COVID-19 patients at 12-months post diagnosis.…”

“…This contrasts against studies which have focused on severe cases of acute COVID-19 where pre-morbid neurological conditions predict cognitive deterioration 3 . Our finding of cognitive decline/failure to improve is in accordance with emerging cognitive 3,48 and brain imaging 49 studies assessing post-acute mild-moderate COVID-19 patients at 12-months post diagnosis. Studies with longer follow-up will be critical to determine if this trend is maintained or whether patients eventually improve 50 .…”

“…In addition, the previous literature on cognition in recovering COVID-19 patients has focused on patients who were hospitalized with severe acute COVID-19 disease (Table S1). Such patients can show extensive neuropsychological impairment (up to 87%) including focal insults due to stroke 3 , although improvement is detected in about half of this population at 12-months 3 . Furthermore, most cognitive studies are cross-sectional, and often have relatively small sample sizes (Table S1).…”

“…There is evidence that SARS CoV-2 is associated with objectively tested cognitive impairment (CI) post-acute illness [1][2][3] (see Table S1) but the extent, trajectory, and the nature of this new condition is unclear. Acute COVID-19 disease severity with its attendant complications is a major differential factor in the nature and extent of cognitive deficits 4 .…”

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

“…They also describe phenomenon such as forgetting why they are in a room, repeating oneself, and word finding difficulties. At 12 months post hospitalization for severe COVID-19 pneumonia, 50% of patients without prior history of dementia or cognitive abnormality had cognitive impairment [152]. Another study showed that 8% of COVID-19 survivors had persistent cognitive dysfunction [143].…”