Long COVID-19: Objectifying most self-reported neurological symptoms

Abstract

Objectives: We aimed to objectify and compare persisting self-reported symptoms in initially hospitalized and non-hospitalized patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by applying clinical standardized measures.

Methods: We conducted a cross-sectional study of adult patients with confirmed SARS-CoV-2 infection including medical history, neurological examination, blood markers, neuropsychological testing, patient-reported outcome measures (PROMs), and brain magnetic resonance imaging (MRI).

Results: Fifty patients with persisting symptoms for at least 4 weeks were included and classified by initial hospitalization status. Median time from SARS-CoV-2 detection to investigation was 29.3 weeks (range 3.3-57.9). Although individual cognitive performance was generally within the normative range in both groups, mostly mild deficits were found in attention, executive functions, and memory. Hospitalized patients performed worse in global cognition, logical reasoning, and processes of verbal memory. In both groups, fatigue severity was associated with reduced performance in attention and psychomotor speed tasks (r_s = -0.40, p < 0.05) and reduced quality of life (EQ5D, r_s = 0.57, p < 0.001) and with more persisting symptoms (median 3 vs. 6, p < 0.01). PROMs identified fatigue, reduced sleep quality, and increased anxiety and depression in both groups but more pronounced in non-hospitalized patients. Brain MRI revealed microbleeds exclusively in hospitalized patients (n = 5).

Interpretation: Regardless of initial COVID-19 severity, an individuals' mental and physical health can be severely impaired in the long-term limitedly objectified by clinical standard diagnostic with abnormalities primarily found in hospitalized patients. This needs to be considered when planning rehabilitation therapies and should give rise to new biomarker research.

Figure 1

Self‐reported acute and long‐term symptoms of 50 patients with COVID‐19 according to hospitalization status. The diagram shows the percentage of self‐reported acute and long‐term symptoms of respective hospitalization group. Group comparison was calculated between hospitalized and non‐hospitalized patients using chi‐square test or Fisher's exact test. Symptoms are ordered according to the frequency of long‐term symptoms in non‐hospitalized patients. Significant differences (p < 0.05) between both groups are indicated by asterisks and included smell and/or taste disturbance, dyspnoea, dizziness, and fever during acute COVID‐19 and smell and/or taste disturbance and headache for long‐term symptoms. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Neuropsychological performance of patients after COVID‐19. Performance in neuropsychological tasks shows an increased dispersion between cognitive domains. Performance is tendentially impaired in time‐based tasks (e.g., alertness tasks, verbal fluency, or trail making test). Overall, neuropsychological test results lie above PR 16 according to published norms adjusted for demographics and, therefore, within normative references. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 3

Association between performance in attention and psychomotor speed tasks (mean composite score) and fatigue scores (FSMC) and affective symptoms (HADS) according to hospitalization status. Performance in attention and psychomotor speed tasks, as mean composite of age and/or education normative PR scores, was negatively associated with increase scores in motor fatigue self‐report (FSMC, [A and B]) in hospitalized (orange) COVID‐19 patients. The severity of affective symptoms (HADS, [C]) was positively associated with the severity of fatigue (FSMC) in both hospitalized and non‐hospitalized (green) patients. Affective symptoms were not associated with performance in attention and psychomotor speed task (D). FSMC, Fatigue Scale for Motor and Cognitive Function; HADS, Hospital Anxiety and Depression Scale. [Colour figure can be viewed at wileyonlinelibrary.com]