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4 Neurophenotypes and recovery trajectories following laboratory-confirmed SARS-CoV-2 infection
- Divya Prabhakaran, Gregory S Day, Bala Munipalli, Beth Rush, Lauren Pudalov, Shehzad Niazi, Emily Brennan, Harry R Powers, Arjun Athreya, Karen Blackmon
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 877-879
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Objective:
Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.
Participants and Methods:The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (> 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P < 0.05.
Results:Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.
Conclusions:Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.
Contributors
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- By Donald Addington, Jean Addington, Kelly Allott, Amanda Baker, Gregor Berger, Michael Berk, Max Birchwood, Warrick J. Brewer, Peter Burnett, Tyrone Cannon, Andrew Chanen, Philippe Conus, Barbara Cornblatt, Thomas Craig, Alex Fornito, David Fowler, Shona M. Francey, John Gleeson, Susy Harrigan, Meredith Harris, Leanne Hides, Christian G. Huber, Henry J. Jackson, Anthony F. Jorm, Eóin Killackey, Joachim Klosterkötter, Martin Lambert, Tim Lambert, Shon Lewis, Don Linszen, Dan Lubman, Nellie Lucas, Craig Macneil, Ashok K. Malla, Max Marshall, Louise K. McCutcheon, Patrick D. McGorry, Catharine McNab, Maria Michail, Anthony P. Morrison, Merete Nordentoft, Ross M. G. Norman, Keith H. Nuechterlein, Christos Pantelis, Lisa J. Phillips, Richie Poulton, Paddy Power, Jo Robinson, Frauke Schultze-Lutter, Jim van Os, José Luis Vázquez-Barquero, Dennis Velakoulis, Darryl Wade, Daniel Weinberger, Durk Wiersma, Stephen J. Wood, Annemarie Wright, Murat Yücel, Alison R. Yung, Robert B. Zipursky
- Edited by Henry J. Jackson, University of Melbourne, Patrick D. McGorry
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- Book:
- The Recognition and Management of Early Psychosis
- Published online:
- 10 August 2009
- Print publication:
- 19 February 2009, pp xi-xvi
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