A Prospective Study of Long-Term Outcomes Among Hospitalized COVID-19 Patients with and without Neurological Complications

Frontera, J. A.; Yang, D.; Lewis, A.; Patel, P.; Medicherla, C.; Arena, V.; Fang, T.; Andino, A.; Snyder, T.; Madhavan, M.; Gratch, D.; Fuchs, B.; Dessy, A.; Canizares, M.; Jauregui, R.; Thomas, B.; Bauman, K.; Olivera, A.; Bhagat, D.; Sonson, M.; Park, G.; Stainman, R.; Sunwoo, B.; Talmasov, D.; Tamimi, M.; Zhu, Y.; Rosenthal, J.; Dygert, L.; Rustic, M.; Ishii, H.; Valdes, E.; Omari, M.; Gurin, L.; Huang, J.; Czseiler, B. M.; Kahn, D. E.; Zhou, T.; Lin, J.; Lord, A.; Melmed, K.; Meropol, S.; Troxel, A.; Petkova, E.; Wisniewski, T.; Balcer, L.; Morrison, C.; Yaghi, S.; Galetta, S.

Background: Little is known regarding long-term outcomes of patients hospitalized with COVID-19. Methods: We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Results: Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N=196 neurological patients and N=186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on [≥]1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 2.03, 95%CI 1.22-3.40, P=0.01), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P=0.01) and were less likely to return to work than controls (41% versus 64%, P=0.04). Cognitive and Neuro-QOL metrics were similar between groups. Conclusions: Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.