SARS-CoV-2 Associated With a Spectrum of Encephalitis

Viral encephalitis. Conceptual illustration showing brain and close-up view of viruses infecting neurons.
SARS-CoV-2’s association with encephalitis was assessed by authors, taking varying clinical presentations, responses to treatment, and outcomes into account.

Infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a wide spectrum of encephalitis with varying clinical presentations, responses to treatment, and outcomes, according to a study recently published in The Journal of Infectious Diseases.

There have been reports of SARS-CoV-2 infection specifically targeting the central nervous system and cases of encephalitis in patients admitted to the intensive care unit for severe respiratory distress. This prospective multicenter study identified all cases of encephalitis associated with SARS-CoV-2 infection.

Data were collected from 13 neurological units in Italy during the coronavirus disease of 2019 (COVID-19) pandemic (ENCOVID-study). Of the total 25 patients with encephalitis positive for SARS-CoV-2 infection who were included, 15 were men, and 10 were women (mean age, 65.9 years). Patients had full infectious screening, cerebrospinal fluid (CSF) analyses, standard electroencephalogram, and brain magnetic resonance imaging (MRI) performed.

Treatment for COVID-19 infection was decided by an infectious disease specialist at each center and included chloroquine/hydroxychloroquine or antiviral treatment. Clinical presentation, laboratory markers, severity of COVID-19 disease, and response to treatment and outcomes were recorded.

Results suggest that SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes. According to study results, the incidence of encephalitis cases was calculated to be 50 in 100,000 cases. At admission, 15 patients (60%) exhibited moderate respiratory COVID-19 disease. Onset of neurological symptoms was concomitant with COVID-19 symptoms in 11 patients (44%), while 12 patients (48%) showed neurological symptoms after a median of 8 days (interquartile range [IQR], 5-12) following COVID-19 symptoms.

Delirium or altered mental status was recorded in 17 patients (68%), aphasia or dysarthria was recorded in 6 patients (24%), and seizures were recorded in 6 patients (24%). CSF analyses showed mild pleocytosis and/or hyperproteinorrachia in 17 patients (68%), despite 19 CSF specimens with a negative SARS-CoV-2 test results. Based on MRI, cases were classified as acute demyelinating encephalomyelitis/acute necrotizing encephalitis (ADEM/ANE; n=3), limbic encephalitis (LE; n=2), encephalitis with normal imaging (E-MRI-; n=13), and encephalitis with MRI alteration (E-MRI+; n=7).

When compared to other encephalitis cases, ADEM and LE cases had a delayed onset (P =.001) and were associated with previous, more severe COVID-19 respiratory involvement. The final clinical outcome was worse in ADEM and E-MRI+ cases compared to LE and E-MRI- encephalitis cases (P =.03). During the study, 3 patients with E-MRI+ and 1 patient with E-MRI- died.

Limitations of the study include absence of autopsy, lack of SARS-CoV-2 evidence in CSF, and potential underestimation of the total number of cases due to patients who could not undergo MRI, electroencephalogram, and MRI due to prominent respiratory insufficiency or death.

Overall, the study authors conclude that, “Further studies focusing on biomarkers are needed in order to disentangle the pathophysiological mechanisms underlying the wide spectrum of CNS involvement in COVID-19 disease and to find the best management strategies for this worldwide growing condition.”

Disclosure: A study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of author’s disclosures.


Pilotto A, Masciocchi S, Volonghi I, et al. Clinical presentation and outcomes of severe acute respiratory syndrome coronavirus 2-related encephalitis: the ENCOVID multicentre study. J Infect Dis. Published online September 28, 2020. doi: 10.1093/infdis/jiaa609/5912547

This article originally appeared on Infectious Disease Advisor