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Case Reports
. 2022 Mar;42(1):114-119.
doi: 10.1002/npr2.12222. Epub 2021 Dec 10.

Severe and long-lasting neuropsychiatric symptoms after mild respiratory symptoms caused by COVID-19: A case report

Ryosuke Jozuka  1 , Hiroki Kimura  1 , Takashi Uematsu  2 , Hidetsugu Fujigaki  3 , Yasuko Yamamoto  3 , Masato Kobayashi  1 , Kazuya Kawabata  2 , Haruki Koike  2 , Toshiya Inada  1 , Kuniaki Saito  3 , Masahisa Katsuno  2 , Norio Ozaki  1
Affiliations
Case Reports

Severe and long-lasting neuropsychiatric symptoms after mild respiratory symptoms caused by COVID-19: A case report

Ryosuke Jozuka et al. Neuropsychopharmacol Rep. 2022 Mar.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is known to cause not only respiratory but also neuropsychiatric symptoms, which are assumed to be derived from a cytokine storm and its effects on the central nervous systems. Patients with COVID-19 who develop severe respiratory symptoms are known to show severe neuropsychiatric symptoms such as cerebrovascular disease and encephalopathy. However, the detailed clinical courses of patients with neuropsychiatric symptoms caused by mild or asymptomatic COVID-19 remain poorly understood. Here, we present a case of COVID-19 who presented with severe and prolonged neuropsychiatric symptoms subsequent to mild respiratory symptoms.

Case presentation: A 55-year-old female with COVID-19 accompanied by mild respiratory symptoms showed delusion, psychomotor excitement, and poor communication ability during quarantine outside the hospital. Considering her diminished respiratory symptoms, her neuropsychiatric symptoms were initially regarded as psychogenic reactions. However, as she showed progressive disturbance of consciousness accompanied by an abnormal electroencephalogram, she was diagnosed with post-COVID-19 encephalopathy. Although her impaired consciousness and elevated cytokine level improved after steroid pulse therapy, several neuropsychiatric symptoms, including a loss of concentration, unsteadiness while walking, and fatigue, remained.

Conclusions: This case suggests the importance of both recognizing that even apparently mild COVID-19-related respiratory symptoms can lead to severe and persistent neuropsychiatric symptoms, and elucidating the mechanisms, treatment, and long-term course of COVID-19-related neuropsychiatric symptoms in the future.

Keywords: COVID-19; case report; cytokines; encephalopathy; long COVID.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
Clinical course of neuropsychiatric symptoms after a mild case of COVID‐19. The figure shows the clinical features, treatment, cerebrospinal fluid (CSF) cytokine analyses, and neuropsychiatric symptoms. Admission was on the 15th day after the initial symptoms. Discharge was on the 67th day. While the severity of the respiratory symptoms was mild, the neurological symptoms were severe. Steroid pulse therapy (three consecutive days with methylprednisolone 1000 mg per week) improved the neuropsychiatric symptoms and reduced the level of cytokines. However, various neurological deficits persisted, some of which are still present
FIGURE 2
FIGURE 2
Cytokine levels during disturbed consciousness and after remission. We compared cerebrospinal fluid (CSF) and plasma cytokine levels during and after treatment for encephalopathy. The results showed increased levels of most cytokines during disturbed consciousness. In many categories, cytokines are reduced with improvements in disturbed consciousness. The concentrations of cytokines/chemokines, including fibroblast growth factor‐2 (FGF‐2), I‐309 (chemokine (C‐C motif) ligand 1 [CCL1]), nerve growth factor (NGF), thymus and activation‐regulated chemokine (TARC), interleukin (IL)‐10, IL‐1β, IL‐6, macrophage inflammatory protein‐1α (MIP‐1α), MIP‐1β, and tumor necrosis factor (TNF)‐α, were measured using a multiplex assay system. The concentration of IL‐8 in both CSF and plasma was measured using an enzyme‐linked immunosorbent assay kit
FIGURE 3
FIGURE 3
Electroencephalogram (EEG) alterations. A, Acute phase in the akinetic mutism state with a diffuse δ wave with frontal lobe dominance. B, Reduced slow wave and reorganization of the background α wave and reactivity after the third course of steroid pulse treatment. C, Remaining slow waves at 4 months after onset. EEG acquisition settings: referential montage; recording speed: 30 s/page; sensitivity: 7 μV/mm; time constant: 0.1 s; high‐frequency filter: 15 Hz
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