Covid-19 pandemic now affects more than two million people worldwide. The neurotropism of the virus is assumed by its frequent association with neurological symptoms (anosmia, ageusia, headaches) but the extent of the central or peripheral nervous system involvement and the associated symptomatology remain poorly known for now. The main objective of this study is to describe the neurological and psychiatric manifestations occurring in the context of Covid-19 infection in patients hospitalized or followed-up in the APHP.SU hospital group. A better understanding of the neuropsychiatric impairment related to Covid-19 would improve the management of these patients in the acute phase, and knowledge of subsequent complications would allow adapting their rehabilitation and follow-up. The precise phenomenological description of these manifestations and the imaging, biology and neuropathology data will be compiled from the data collected by the physicians in charge of these patients as part of their inpatient or outpatient care. This study will also allow collecting unusual clinical manifestations from patients followed for neurological or psychiatric pathology in hospital departments and presenting a Covid-19 infection, in order to optimize the reorganization of their management, follow-up and rehabilitation in the epidemic context.
Pandemic context In December 2019, the first cases of SARS-CoV-2 coronavirus infection
(Covid-19) appeared in Wuhan, Hubei Province, China. The virus quickly spread to other
Chinese provinces and then to the rest of the world. The first cases in France were diagnosed
on 23 January 2020 in patients who had been in China, and the number of cases rapidly
increased to 100 confirmed cases on 29 February 2020. As of 16 April, 106,206 patients had
been confirmed, 6,457 patients were hospitalized in intensive care units, and the number of
deaths linked to Covid-19 in hospital was 10,643 (government.fr). At the same date, more than
2,065,906 cases were confirmed worldwide, with more than 137,124 deaths (jhu.edu). The most
commonly reported clinical manifestation of SARS-CoV-2 infection is an infectious syndrome
associated with respiratory signs.
Neurological and psychiatric manifestations of Covid-19 To date, little is known about
neurological and psychiatric manifestations of Covid-19. Some authors suggested a significant
proportion of patients with central neurological manifestations such as headache, confusion,
seizures or strokes. Some cases of COVID-19 encephalitis have also been reported: a case of
acute haemorrhagic encephalitis, and a case of encephalitis with seizure and positive
SARS-CoV-2 PCR in the CSF. Neurological impairment of Covid-19 has been proposed as a
contributing mechanism to respiratory failure in some patients with severe disease. Anosmia
and ageusia are now recognized as common symptoms of the infection. Cases of Guillain-Barré
syndrome and probable myelitis (without radiological confirmation) have also been described.
Myalgia is frequently reported in patients with Covid-19 infection, but no cases of
documented myopathy have been reported to date.
Patients with Covid-19 infection may also present systemic encephalopathy in the context of
severe respiratory failure, associated organ failure (renal, hepatic), and iatrogenicity.
Patients hospitalized in intensive care unit for severe forms of the infection frequently
present with confusion, and sometimes persistent cognitive disorders such as a dysexecutive
syndrome, attention disorders, spatio-temporal disorientation. A high frequency of clinical
signs of cortico-spinal bundle damage and leptomeningeal contrast images on cerebral MRI has
also been reported.
Regarding psychiatric manifestations, a high prevalence of anxiety disorders and depressive
syndromes was noted in patients with Covid-19. Post-traumatic stress disorder may also occur
in these patients, particularly those who have suffered from severe forms of stress and have
been hospitalized in intensive care units.
SARS-CoV-2 is a member of the coronavirus family and bears a strong similarity to other
coronaviruses such as SARS-CoV or MERS-CoV. Clinical and preclinical knowledge of other
coronaviruses suggests neurotropism of viruses of this family. In particular, infection with
SARS-CoV-2 or NCoV-OC43 may cause encephalitis or encephalomyelitis. The SARS-CoV-2 virus
adheres to cell membranes by interaction with ACE2 receptors, which are highly expressed on
the surfaces of neurons and glial cells. The ACE2 receptor is particularly expressed in the
brainstem and in regions involved in cardiovascular control including the paraventricular
nucleus, the nucleus of the solitary tract. The virus could reach the nervous system via
systemic circulation (viremia) or via ethmoidal microcirculation via the olfactory
epithelium. Indeed, animal studies have shown that SARS-Cov can invade the brain via the
olfactory epithelium via the nasal route and cause neuronal death. The virus could also
infect the brain through trans-synaptic transmission from the olfactory epithelium through
the ethmoidal floor to the olfactory bulb. Another mechanism of neurological damage related
to Covid-19 infection could be the initiation of an immune reaction with the release of
cytokines and other inflammatory proteins, leading to a breakdown of the blood-brain barrier,
which amplifies neuro-inflammatory processes. Systemic inflammation and cytokines may also
promote ischemic stroke. Severe coagulopathies have been reported.
Covid-19 and pre-existing neurological and psychiatric disorders SARS-CoV-2 infection could
lead to the aggravation of certain pre-existing neurological and psychiatric disorders, but
the potential impact of the infection in the short, medium and long term on these pathologies
is still unknown.
Indeed, infections are a classic aggravating factor in many neurological pathologies, such as
autoimmune pathologies, metabolic pathologies, and also neurodegenerative pathologies. Brain
inflammation is recognised as an important mechanism of neurodegenerative pathologies and has
also been implicated in psychiatric pathologies such as schizophrenia and depression.
Patients with cardiac or respiratory damage, particularly in the context of neuro-muscular
pathologies, could particularly develop severe forms of infection. Patients with
neurodegenerative pathologies often represent an elderly population, and therefore also at
risk of severe forms of infection. Patients followed for inflammatory or neuro-oncological
pathologies and undergoing immunosuppressive treatments or chemotherapy also represent a
at-risk population. SARS-CoV-2 infection could also worsen certain psychiatric pathologies.
Public interest research Neurological and psychiatric manifestations have been reported in
patients with Covid-19 but the different neuropsychiatric expressions of Covid-19 infections
are currently not well characterized.
A better understanding of the neurological and psychiatric impairment related to Covid-19
could improve management of the patients in the acute phase.
Knowledge of neurological and psychiatric complications subsequently occurring would allow
adapting the follow-up of these patients. The inclusion of prospective long-term follow-up
data is crucial in the overall understanding of the neuropsychiatric disorders of Covid-19.
Neurological complications are likely to occur at a distance from the infection or to be
lately diagnosed, for instance, in patients who have been in intensive care. The collection
of data from the rehabilitation follow-up of these patients is crucial in this context.
The precise phenomenological description of these manifestations and the collection of
imaging, biological and neuropathological data may also allow establishing hypotheses on the
pathophysiology of the neurological damage caused by Covid-19.
The impact of Covid-19 infection on pre-existing neurological and psychiatric pathologies is
not known. This knowledge would optimize the reorganization of the management, follow-up and
rehabilitation of these patients in the epidemic context.
In this observational, retrospective, multicentre study, the investigators aim at i)
describing the clinical and paraclinical manifestations of patients with neurological or
psychiatric manifestations of Covid-19 infection, and ii) describing changes in the clinical
trajectories of patients with Covid-19 infection, initially followed for neurological or
psychiatric pathologies.
Inclusion Criteria:
- Age of 18 years or over
- Patient followed for a neurological or psychiatric pathology OR Patient consulting and
presenting a neurological or psychiatric impairment AND
- Presenting a COVID-19 infection defined by at least one of the following three
criteria:
- Biological diagnosis by any method for direct detection of the virus (Covid-19
positive PCR) or recent infection (serology)
- Typical chest imaging (CT scan or X-ray) in an epidemic area
- Clinical-biological data leading to a strong suspicion of current or past
Covid-19 infection
- Non-opposition of the participant, relative or guardian to the research
Exclusion Criteria:
- Patient under safety measure
Hôpital Pitié Salpétrière
Paris, France
Investigator: cécile Delorme, MD
Contact: 1 42 16 18 02
cecile.delorme@aphp.fr
CECILE DELORME, MD
142161802 - +33
cecile.delorme@aphp.fr
Jean-Christophe CORVOL, MD,PHD
142161799 - +33
jean-christophe.corvol@aphp.fr