3. Discussion
We present the first description of cranial polyneuropathy involvement in a child infected with SARS-COV-2. Although COVID-19 is mainly associated with a respiratory illness, neurological involvement shall not be underestimated as it has been reported in more than 35% cases in a recent study of 214 patients (6). Three types of neurological symptoms have been described: (i) central nervous system manifestations as dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, or seizure, (ii) peripheral nervous system manifestations as taste impairment, smell impairment, vision impairment, and neuropathic pain, (iii) and skeletal muscular injury manifestations. Theses neurological manifestations tended to occur early in the illness (median time, 1-2 days), in patients with severe infection, respiratory symptoms of COVID-19 developing secondarily as in our observation. Of the 214 patients, only 5 had isolated peripheral nerve damage, 4 of which progressed to severe COVID-19 as in our observation.
Our observation could be considered an atypical case of Guillain-Barré syndrome, with exclusive craniofacial impairment. One case of Guillain-Barré syndrome associated with SARS-CoV-2 was described in a 61 year old woman (7), recently followed by the description of five patients with Guillain–Barré syndrome 5 to 10 days after the onset of COVID-19, 4 of them presenting with facial weakness or diplegia (8). The pathophysiology of this peripheral nerve damage is not yet established and may not be unequivocally related to a per or post infectious immunological mechanism as seen with other infectious agents (9). Indeed, the cranial polyneuropathy we report was clinically inaugural, in a heavily immunocompromised patient. Besides, we did not observed the typical Guillain Barre CSF change with high protein without high cellularity. In any case, in our observation as in the Toledano series, the extent of the facial nerves involvement is striking. All these particularities point to the possible involvement of SARS-Cov 2 neurotropism.
Over the years, some coronaviruses have been associated with neurological diseases in animals. Among the five different coronaviruses able to infect humans, at least three strains are neuroinvasive and neurotropic (10,11). Early in 2002 and 2003, studies on the samples from patients with SARS revealed the presence of SARS-CoV particles in the brain, where they were located almost exclusively in the neurons (9). Experimental studies carried out in mice infected with coronavirus have shown that the brain stem might be strongly impacted (12,13) which raises the hypothesis that an impairment of the central nervous system might be involved in the respiratory failure (14). A potential tropism for cranial nerves has also been disccused, especially with the olfactory nerves and bulbs acting as a doorway to the cerebral nervous system upon a primary nasal infection.
In our patient, no pathogen other than SARS-CoV 2 could be detected, despite two lumbar punctures and extensive research. However, it remains possible that viral co-infections (EBV and HSV) interplayed with the coronavirus in the pathogenesis of this polyneuropathy. Moreover, the conditioning, the resulting immunosuppression or the pre-existing cerebral vasculopathy may also have play a role even if this type of cranial polyneuropathy had not been reported as side effect of conditioning nor in sickle cell disease.
In conclusion, peripheral nerve involvement is rarely described in COVID-19 but might predict an aggressive course of the disease, and facial or cranial nerve involvement may be suggestive. By any means, physicians should consider SARS-CoV-2 infection in immunocompromised patients with peripheral nerve abnormalities even without respiratory manifestations or fever. A prompt diagnosis could prevent delayed management and prevention of transmission of the virus.
4. Conflict of Interest: The other authors have no conflicts of interest to disclose.