The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study

  1. Andrea Pilotto
  2. Stefano Masciocchi
  3. Irene Volonghi
  4. Elisabetta del Zotto
  5. Eugenio Magni
  6. Valeria De Giuli
  7. Francesca Caprioli
  8. Nicola Rifino
  9. Maria Sessa
  10. Michele Gennuso
  11. Maria Sofia Cotelli
  12. Marinella Turla
  13. Ubaldo Balducci
  14. Sara Mariotto
  15. Sergio Ferrari
  16. Alfonso Ciccone
  17. Fabrizio Fiacco
  18. Alberto Imarisio
  19. Barbara Risi
  20. Alberto Benussi
  21. Enrico Premi
  22. Emanuele Focà
  23. Francesca Caccuri
  24. Matilde Leonardi
  25. Roberto Gasparotti
  26. Francesco Castelli
  27. Gianluigi Zanusso
  28. Alessandro Pezzini
  29. Alessandro Padovani
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Abstract

Importance

Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes yet.

Objective

to describe the clinical phenotype, laboratory and neuroimaging findings of encephalitis associated with SARS-CoV-2 infection, their relationship with respiratory function and inflammatory parameters and their clinical course and response to treatment.

Design

The ENCOVID multicentre study was carried out in 13 centres in northern Italy between February 20th and May 31st, 2020. Only patients with altered mental status and at least two supportive criteria for encephalitis with full infectious screening, CSF, EEG, MRI data and a confirmed diagnosis of SARS-CoV-2 infection were included. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded.

Results

Out of 45 cases screened, twenty-five cases of encephalitis positive for SARS-CoV-2 infection with full available data were included. The most common symptoms at onset were delirium (68%), aphasia/dysarthria (24%) and seizures (24%). CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis.

Conclusions and relevance

We found a wide clinical spectrum of encephalitis associated with COVID19 infection, underlying different pathophysiological mechanisms. Response to treatment and final outcome strongly depended on specific CNS-manifestations.

Question

what are the phenotypes of encephalitis associated to SARS-CoV-2 infection?

Findings

25 cases of encephalitis in SARS-CoV-2 infection were included in a prospective observational multi-centre study. Encephalitis cases in COVID-19 exhibited a wide heterogeneity in terms of clinical features, CSF, MRI findings, response to treatment and outcomes with 13 cases with normal MRI, 7 with heterogeneous MRI alterations and rarer ADEM/limbic encephalitis cases.

Meaning

heterogeneity of presentation, response to treatment and outcomes of encephalitis of COVID-19 underlines different pathophysiological mechanisms

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