Prevalence and trajectories of neuropsychological post-COVID-19 symptoms in initially hospitalized patients

Abstract

Objective: To investigate the prevalence and trajectories of post-COVID-19 neuropsychological symptoms.

Design: Prospective longitudinal multicentre cohort study.

Subjects: A total of 205 patients initially hospitalized with SARS-CoV-2 (COVID-19).

Methods: Validated questionnaires were administered at 9 months (T1) and 15 months (T2) post-hospital discharge to assess fatigue, cognitive complaints, insomnia, anxiety, depression, and post-traumatic stress symptoms.

Results: Analyses included 184 out of 205 patients. Approximately 50% experienced high cognitive complaints at T1 and T2, while severe fatigue affected 52.5% at T1 and 55.6% at T2. Clinically relevant insomnia scores were observed in 25% of patients at both time-points. Clinically relevant anxiety scores were present in 18.3% at T1 and 16.7% at T2, depression in 15.0% at T1 and 18.9% at T2, and PTSD in 12.4% at T1 and 11.8% at T2. Most symptoms remained stable, with 59.2% of patients experiencing at least 1 persistent symptom. In addition, 31.5% of patients developed delayed-onset symptoms.

Conclusion: Post-COVID-19 cognitive complaints and fatigue are highly prevalent and often persist. A subgroup develops delayed symptoms. Emotional distress is limited. Screening can help identify most patients experiencing long-term problems. Future research should determine risk factors for persistent and delayed onset symptoms.

Fig. 1

Sankey flow diagrams visualizing the prevalence of scores classified as: (A) persistent, (B) delayed onset, (C) remitted, and (D) absent symptoms per screening instrument. CLC-IC: Checklist for Cognitive Consequences following Intensive Care Admission; FSS: Fatigue Severity Scale; ISI: Insomnia Severity Index; HADS-A: Hospital Anxiety and Depression Scale – Anxiety subscale; HADS-D: Hospital Anxiety and Depression Scale – Depression subscale; PC-PTSD-5: Primary Care Post-Traumatic Stress Disorder Screen for DSM-5; T1: time-point 1 (9 months post-hospital discharge), T2: time-point 2 (15 months post-hospital discharge); n: Total number of patients included per measurement construct. Red nodes correspond to the number of patients whose score was classified as clinical (score above the cut-off), at T1 on the left and T2 on the right. Conversely, green nodes represent patients with non-clinical scores (score below the cut-off). The arcs in the diagram illustrate trajectories: grey arcs signify no change in score classification, typical of persistent or absent symptoms; red arcs indicate an increase of scores classified as delayed onset symptoms, and green arcs depict decreasing scores classified as remitted symptoms. Numbers indicate the count of patients in each category, with arrows illustrating the number of patients who transitioned from one category to another, where red indicates the delayed onset of new clinical symptoms, and green represents remission of such.

Fig. 2

Magnitude of score change between T1 (9 months post-hospital discharge) and T2 (15 months post-hospital discharge) reported by patients who had at least 1 score classified as (A) delayed onset or (B) remitted symptom. CLC-IC: Cognitive Complaints following Intensive Care Admission, FSS: Fatigue Severity Scale, ISI: Insomnia Severity Index, HADS-a: Hospital Anxiety and Depression Scale – anxiety subscale, HADS-d: Hospital Anxiety and Depression Scale – depression subscale, PC-PTSD: Primary Care Post Traumatic Stress Disorder Screen for DSM-5, n: number of individuals per group. Note: The figure displays percentages of score change between T1 (9 months post-hospital discharge) and T2 (15 months post-hospital discharge) per screening instrument and the corresponding number of patients to whom it applies. Delayed onset symptoms (i.e. below the clinical cut-off at T1 but above cut-off at T2) are displayed in red and remitted symptoms (i.e. above the clinical cut-off at T1 and below cut-off at T2) in green.

Fig. 3

Correlations between the number of unfavourable symptom trajectories (persistent and delayed-onset symptoms) per patient and (A & B) passive coping, (C & D) quality of life, and (E & F) social support at 9 months (T1) and 15 months (T2) after hospital discharge. T1: time-point 1 (9 months post-hospital discharge); T2: time-point 2 (15 months post-hospital discharge); Nb unfavourable trajectories: number of unfavourable trajectories; UCL: Utrecht Coping List – passive coping subscale; EQ-5D-5L: EuroQol 5D-5L; SSL-12-I: Social Support List (12-item version); r: Pearson correlation coefficient. Note: y-axis comprises the number of unfavourable symptom trajectories (persistent and delayed-onset symptoms) per patient, while the x-axes illustrate the corresponding scores on the 3 psychosocial variables at either time-point 1 or time-point 2. Patients may exhibit a range of unfavourable trajectories, with a minimum of 0 (indicating the absence of persistent or delayed-onset symptoms on all screening instruments) and a maximum of 6 (signifying the presence of persistent or delayed-onset symptoms across all screening instruments).