Autoimmune Encephalitis in COVID-19 Infection: Our Experience and Systematic Review of the Literature

Abstract

The neurologic complications of COVID-19 infection are frequent in hospitalized patients; a high percentage of them present neurologic manifestations at some point during the course of their disease. Headache, muscle pain, encephalopathy and dizziness are among the most common complications. Encephalitis is an inflammatory condition with many etiologies. There are several forms of encephalitis associated with antibodies against intracellular neuronal proteins, cell surfaces or synaptic proteins, referred to as autoimmune encephalitis. Several case reports published in the literature document autoimmune encephalitis cases triggered by COVID-19 infection. Our paper first presents our experience in this issue and then systematically reviews the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also discusses the possible pathophysiological mechanisms of auto-immune-mediated damage to the nervous system. This review contributes to improve the management and prognosis of COVID-19-related autoimmune encephalitis.

Keywords: COVID-19 infection; autoimmune encephalitis; voltage-gated potassium channels antibody.

Figure 1

PRISMA flow diagram for the systematic review.

Figure 2

Cerebral MRI, FLAIR sequences revealing mild periventricular microvascular changes and cerebral atrophy.

Figure 3

EEG examination revealing bilateral, slow-wave discharges, and spikes on the frontal, parietal and temporal derivations.

Figure 4

Graphical representation of the proposed mechanisms for neuro-invasion. Endothelial angiotensin-converting enzyme 2 receptors (ACE2-receptors), anti-aquaporin 4 (AQP4).

Figure 5

Graphical representation of the proposed mechanisms for viral induced autoimmunity. Key mechanism for viral induced autoimmunity: (1) molecular mimicry-cross-reactive response against virus and self-antigens leading to lymphocyte activation; (2) bystander activation—the released self-antigens are taken by the antigen presenting cells(APC) and presented to naïve T cells which become responsive. Simultaneously, the innate immune system triggers the production of proinflammatory cytokines and chemokines and initiate self-tissue destruction that generate self-tissue antigens mimicking viral antigens; (3) epitope spreading—the viral infection produce futher damage and release of more self-antigens with subsequent activation of auto-reative T cells. When the damage involves the central nervous system it triggers T and B cells activation and maintain a pro-inflammatory environment.