We report a 57-year-old female with mild but disabling neuropsychological symptoms 6 months after mild COVID-19. During the acute infection, the patient self-referred to a hospital after a positive result of SARS-CoV-2 PCR-testing, which was performed in an outpatient setting due to fever, headache, ubiquitous limb pain, and diarrhea. Upon admittance, vital parameters including peripheral oxygen levels were normal. Laboratory routine examinations were unremarkable despite slightly increased levels of C-reactive protein. Neither intensive care, nor ventilation were required during the hospitalization, and she was discharged home after 5 days. Two weeks after the acute illness, she experienced impaired concentration and action planning. As this condition persisted for several months, preventing her from resuming her professional activity as a nurse and limiting herself in the organization of her activities of daily living, she was referred to our university hospital by a local neurologist. A detailed neurological examination did not detect any abnormalities. In particular, no apraxia or aphasia, and no hypokinetic-rigid signs were found. Apart from a depressive episode in the past, her medical history was unremarkable. A brain MRI examination, standardized testing of the olfactory function (
Supplement – BSIT), serologic examination for infectious and autoimmune disease, and further laboratory examinations were likewise normal (
Supplement - Laboratory analysis). Workup for both synaptic and paraneoplastic antineuronal antibodies, investigated in serum, was negative (
Supplement – Antineuronal antibodies). CSF routine examination was unremarkable, except for a non-specific elevation of CSF protein levels (
Supplement – Standard CSF analysis). However, an in-depth standardized neuropsychological assessment revealed relevant impairment regarding “attention”, “alertness” and “working memory”, and the patient scored high on distress and fatigue assessments (Supplementary Table
1). Serologic investigations (
Supplement – Methods) revealed positive IgG antibody titers against the S1 (4.2) and the nucleocapsid (NCP) protein (1.7) of SARS-CoV-2 (EUROIMMUN, Lübeck, Germany, values < 0.8 are considered negative, 0.8–1.1 borderline, > 1.1 positive). In comparison to healthy control subjects (
n = 2), we detected elevated levels of SARS-CoV-2- specific IgG S1 antibodies and a trend towards elevated IgG nucleocapsid antibodies in the CSF (Table
1;
Supplement – Methods). Furthermore, as neurotransmitter alterations have been reported in individuals with mild cognitive impairment [
6] and animal models of coronavirus infection [
2], we investigated levels of gamma-aminobutyric acid (GABA), glutamate, and glutamine in the CSF (
Supplement – Methods), but did not observe any significant differences between the index patient and controls subjects (
n = 3) (Table
1).
Table 1
CSF SARS-CoV-2-specific IgG antibodies against the spike (S1) and the nucleocapsid (NCP) protein and neurotransmitter levels in the index patient compared to control subjects
CSF SARS-CoV-2 antibodies |
IgG anti-S1, 1:2 | 0.450 | 0.044 +/− 0.009 (n = 2) | 0.017 |
IgG anti-S1, 1:5 | 0.190 | 0.039 +/− 0.009 (n = 2) | 0.048 |
IgG anti-NCP, 1:2 | 0.150 | 0.036 +/− 0.015 (n = 2) | 0.102 |
IgG anti-NCP, 1:5 | 0.073 | 0.024 +/− 0.007 (n = 2) | 0.114 |
CSF neurotransmitter levels |
Glutamate (μM) | 3.70 | 4.53 +/− 0.82 (n = 3) | 0.546 |
GABA (μM) | 0.30 | 0.32 +/− 0.02 (n = 3) | 0.434 |
Glutamine (μM) | 604 | 634 +/− 82 (n = 3) | 0.820 |