COVID-19-Associated Encephalopathy: Systematic Review of Case Reports

Abstract

Background and purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system, but there are also several reports of the involvement of the central nervous system, with one of the manifestations being encephalopathy. The relatively new emergence of COVID-19 means that few studies have investigated the clinical profile of encephalopathy associated with this disease. This study aimed to determine the clinical profile, laboratory, and imaging results of encephalopathy associated with COVID-19.

Methods: Three databases, namely PubMed/MEDLINE, Embase, and Scopus, were systematically searched for case reports and case series related to COVID-19-associated encephalopathy published from January 1, 2019 to July 20, 2020.

Results: This review included 24 studies involving 33 cases. The most-reported neurological symptoms were disorientation/confusion (72.72%), decreased consciousness (54.54%), and seizures (27.27%). Laboratory examinations revealed increases in the C-reactive protein level (48.48%), the lactate dehydrogenase level (30.30%), and lymphopenia (27.27%). Brain imaging did not produce any pathological findings in 51.51% of the cases. Electroencephalography showed generalized slowing in 45.45% of the cases. Elevated protein (42.42%) and lymphocytosis (24.24%) were found in the cerebrospinal fluid. Fifteen patients were reportedly discharged from the hospital in a stable condition, while four cases of mortality were recorded.

Conclusions: The clinical, laboratory, and imaging findings in this review support the hypothesis that cerebral damage in COVID-19-associated encephalopathy is caused by cytokine-immune-mediated inflammation rather than by direct invasion.

Keywords: COVID-19; SARS-CoV-2; encephalitis; encephalopathy; nerve inflammation; neuro immune.

Fig. 1. Flow chart of study selection.

Fig. 2. Cytokine-immune-mediated inflammation and pathomechanism in COVID-19-associated encephalitis. ACE₂, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemotactic protein 1; NF-κB, nuclear factor kappa B; TGF, tumor growth factor; VCAM-1, vascular cell adhesion molecule 1; Th17, T helper 17.