Clinical Manifestation, Management, and Outcomes in Patients with COVID-19 Vaccine-Induced Acute Encephalitis: Two Case Reports and a Literature Review

Abstract

Introduction: Vaccination is one of the best strategies to control coronavirus disease 2019 (COVID-19), and multiple vaccines have been introduced. A variety of neurological adverse effects have been noted after the implementation of large-scale vaccination programs. Methods: We reported two rare cases of possible mRNA-1273 vaccine-induced acute encephalitis, including clinical manifestations, laboratory characteristics, and management. Results: The clinical manifestations might be related to hyperproduction of systemic and cerebrospinal fluid (CSF) cytokines. mRNA vaccines are comprised of nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA, which is translated into SARS-CoV-2 spike protein by the host’s ribosomes, activating the adaptive immune response. Exposed mRNA or vaccine components may also be detected as antigens, further resulting in aberrant proinflammatory cytokine cascades and activation of immune signaling pathways. Both patients exhibited significant clinical improvement after a course of steroid therapy. Conclusion: The use of COVID-19 vaccines to prevent and control SARS-CoV-2 infections and complications is the most practicable policy worldwide. However, inaccurate diagnosis or other diagnostic delays in cases of vaccine-induced acute encephalitis may have devastating and potentially life-threatening consequences for patients. Early diagnosis and timely treatment can result in a favorable prognosis.

Encephalitis following COVID-19 Vaccination: A Systematic Review

“…These include functional neurological disorder symptoms, such as altered mental status, autoimmune encephalitis (AE), acute disseminated encephalomyelitis (ADEM), dizziness, myalgia, fatigue, cognitive impairment, gait instability, facial palsy, Guillain–Barré syndrome (GBS), convulsions, strokes, transverse myelitis, chronic fatigue syndrome, and acute encephalopathy [ 9 , 10 ]. Recently, major neurological complications indicative of vaccination-related autoimmune encephalitis and acute encephalitis after the first dose of mRNA COVID-19 vaccines were reported [ 11 , 12 , 13 , 14 , 15 ]. Notably, acute disseminated encephalomyelitis (ADEM) was consistently reported after the viral vector-based vaccines or inactivated viral vaccine (AstraZeneca, Sputnik V, Sinopharm) [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Anti-NMDA Autoimmune Encephalitis Post-COVID-19 Vaccination in a Pediatric Patient: A Case Report

“…13 In certain individuals the vaccine components and the exposed mRNA might be recognized as antigens and trigger a cascade of proinflammatory cytokines and activate an immune response. 17 The post-vaccinal expression of proinflammatory cytokines (i.e., interleukin-1, interleukin-6, tumor necrosis factor-α, and prostaglandin-E2) is an important part of the pathogenicity as these cytokines may reach the brain and result in neuroinflammation following the activation of microglia. 18 The triggered immune response and the high levels of cytokines can lead to inflammatory symptoms and possible organ failure.…”

“…17 Furthermore, the spike proteins can distort the blood-brain barrier increasing its permeability and allowing the inflammatory material to reach the CNS. 17 The causality labeling criteria of neurological adverse events following immunization by Butler et al classify cases as probable, possible, or unlikely based on the temporal relationship, individual risk factors, and the likelihood of an alternative etiology. 19 A probable causal link is defined by a typical timeframe of less than 6 weeks, a lack of an alternative etiology, and possible risk factors identified by clinical, laboratory, radiological, and electrophysiological assessment.…”

“…The pathogenesis of vaccine-related neurological manifestation, has been postulated to be secondary to the expression of spike protein by human cells (after translation of the mRNA COVID-19 vaccine), which elicit an inflammatory response similar to that induced by the virus itself (13). In certain individuals the vaccine components and the exposed mRNA might be recognized as antigens and trigger a cascade of proinflammatory cytokines and activate an immune response (17). The post-vaccinal expression of proinflammatory cytokines (i.e., interleukin-1, interleukin-6, TNF-α, and PG-E2) is an important part of the pathogenicity as these cytokines may reach the brain and result in neuroinflammation following the activation of microglia (18).…”

“…The post-vaccinal expression of proinflammatory cytokines (i.e., interleukin-1, interleukin-6, TNF-α, and PG-E2) is an important part of the pathogenicity as these cytokines may reach the brain and result in neuroinflammation following the activation of microglia (18). The triggered immune response and the high levels of cytokines can lead to inflammatory symptoms and possible organ failure (17). Furthermore, the spike proteins can distort the blood brain barrier increasing its permeability and allowing the inflammatory material to reach the central nervous system (17).…”