Neuropsychiatric phenotype of post COVID-19 syndrome in non-hospitalized patients

Abstract

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

Keywords: COVID-19; MFI-20; PCFS; neuropsychiatric disorders; post COVID-19 syndrome.

Figure 1

Study design and description of study cohort. (A) Flowchart of patient distribution. (B) Age between cohort and control. (C–E) Comparison of antibody levels between cohort and control. (E) Concentration of neutralizing antibodies (binding antibody units per milliliter (BAU/ml) tended to be higher in the control (p = 0.012). While the concentration of anti–nucleocapside antibodies did not differ, the control group had significantly higher concentrations of antibodies against the receptor binding domain (anti–RBD; p = 0.0046), however possible vaccination–associated influences were not examined.

Figure 2

Psychiatric–psychosomatic assessment. (A–E) The study cohort revealed significantly higher test results in all psychiatric–psychosomatic self–questionnaires when compared to the neuropsychiatrically unaffected control cohort (all p-values < 0.001). (F–I) Significant correlations of the Post COVID Functional Scale (PCFS) with the total scores of the MFI–20 (Fρ = 0.66, p < 0.001), PHQ–9 (Gρ = 0.59, p < 0.001) and PHQ–15 (Hρ = 0.56, p < 0.001) and GAD–7 (Iρ = 0.4, p < 0.001) in the total cohort (N = 219).

Figure 3

Neurocognitive assessment in the study cohort (N = 105). Upper row, correlation with age: Significant correlations of the MoCA (A ρ = −0.34, p < 0.05), time [in seconds] in the Trail making test A (B ρ = 0.44, p < 0.05) and Trail making test B (C ρ = 0.44, p < 0.05) with age. Correlation of number of correct words in the semantic fluency task with age did not stay significant after adjustment for multiple comparisons (D ρ = −0.21, p = 0.34). Lower row, correlation with post COVID functional scale (PCFS): Not significant correlations of the MoCA (E ρ = −0.06, p = 1), time [in seconds] in the Trail making A (F ρ = 0.2, p = 0.33) and Trail making B (G ρ = 0.08, p = 1) and the number of correct words in the semantic fluency task (H, ρ = −0.2, p = 0.2) with the PCFS.