The ENERGY Project: A Global Collaborative Response to the Neurological Impact of COVID-19

In the early months of the COVID-19 pandemic, when uncertainty shaped clinical practice worldwide, neurologists rapidly recognised that SARS-CoV-2 was not only a pathogen affecting the respiratory system but also a major neurological challenge. In response to this urgent need for structured evidence, the European Academy of Neurology launched the EAN NEuro-covid ReGistrY (ENERGY), an ambitious international initiative designed to capture, understand, and quantify neurological manifestations associated with COVID-19.

Since its launch in 2020, ENERGY has grown into a comprehensive global registry dedicated to neuro-COVID. Thanks to the commitment of clinicians worldwide, the registry has collected data from 4,105 patients, representing 10,546 clinical visits, including 6,441 follow-up assessments. Contributions from 57 investigators and their teams across 44 centres in 30 countries transformed ENERGY into a truly international scientific collaboration during an unprecedented global health crisis.

Advancing Knowledge in a Time of Uncertainty

ENERGY was established to provide robust epidemiological data on neurological manifestations in patients with COVID-19 across outpatient services, emergency departments, and hospital settings. By systematically collecting clinical and demographic information by neurologists, the initiative created  structured evidence at a time when clinicians urgently needed guidance.

The registry documented the wide spectrum and severity of neurological involvement in SARS-CoV-2 infection. Analyses revealed that neurological manifestations were highly prevalent and associated with significant clinical burden, including cognitive dysfunction, stroke, sleep–wake disturbances, peripheral neuropathies, and movement disorders^1,2. Importantly, the data demonstrated that neurological involvement was linked to poorer clinical outcomes and increased mortality risk^3,4, underscoring the critical role of neurological assessment in the management of COVID-19 patients.

ENERGY also provided essential insights into long-term consequences. Follow-up analyses showed that many patients experienced persistent neurological symptoms months after infection, with  cognitive impairment, sleep disorders and anosmia/dysgeusia among the most common complaints and manifestations^1,3. These findings contributed to the growing understanding of post-COVID neurological conditions and their predictors¹.

Scientific Output and Global Impact

To date, five peer-reviewed publications based on the ENERGY database have contributed towards the understanding of Neuro-COVID^1-5. These studies clarified predictors of functional outcome, characterised neurological phenotypes, identified risk factors for poor prognosis, and contributed to global collaborative research efforts examining neurological complications of COVID-19.

In addition, the ENERGY group has recently submitted a new paper⁶ analysing the impact of the different COVID waves on neurological manifestations, further expanding the knowledge gained from the registry.

A Collective Achievement

The success of ENERGY reflects the dedication of its leadership and the global network of investigators who contributed data under exceptionally challenging circumstances. The project was overseen by the ENERGY Core Group, Profs. Elena Moro, Raimund Helbok, the late

Ettore Beghi, Claudio L. Bassetti, and Dr Maurizio Leone, with the help of the EAN office, Dr Maria Lolich and Ms. Maria Konti, together with an international community of investigators and collaborating centres.

The ENERGY working group extends its sincere appreciation to all principal investigators, participating centres, and clinical teams who contributed to ENERGY. Thanks to the active participation of the patients who took part in the study, together with the dedication of the investigators, a unique global resource was created that has profoundly advanced our understanding of COVID-19 and its neurological impact.

ENERGY stands as a testament to what coordinated international collaboration can achieve — even in the most challenging of times.

ENERGY Principal Investigators:

References:

1. Leone MA, Helbok R, Bianchi E, et al. Outcome predictors of post-COVID conditions in the European Academy of Neurology COVID-19 registry. J Neurol. 2024.
2. Beghi E, Moro E, Davidescu EI, et al. Comparative features and outcomes of major neurological complications of COVID-19. Eur J Neurol. 2023.
3. Beghi E, Helbok R, Ozturk S, et al. Short- and long-term outcome and predictors in an international cohort of patients with neuro-COVID-19. Eur J Neurol. 2022.
4. Chou SHY, Beghi E, Helbok R, et al. Global incidence of neurological manifestations among patients hospitalized with COVID-19. JAMA Netw Open. 2021.
5. Beghi E, Helbok R, Crean M, et al. The European Academy of Neurology COVID-19 registry (ENERGY): an international instrument for surveillance of neurological complications in COVID-19. Eur J Neurol. 2021.
6. Leone MA, Helbok R, Bianchi E, et al. The spectrum of acute and post-acute neurological involvement over four waves of COVID-19 infection. Manuscript submitted for publication.

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