The clinical picture of our patient was in keeping with GBS according to Brighton criteria, with increasing flaccid weakness of the limbs, areflexia, albumino-cytologic dissociation and consistent neurophysiologic data. Other causes of concurrent neurotoxicities were also excluded, as hydroxichloroquine generally accounts for different side effects and antiretrovirals had yet to be administered when she started having neurological symptoms. Intensive supportive care and the need for strict isolation impaired clinical and instrumental assessment of the neurological aspect, despite being critical to determine prognosis.
Remarkably, contrary to the previous reported case with COVID-19 [2], our patient developed neurological deficits a week after the onset of respiratory symptoms and they progressed simultaneously; therefore, the evolution of her clinical picture does not support the typical post-infectious pattern of GBS and it could rather resemble a form of acute para-infectious paralysis that has already been associated with some viruses, such as ZIKV [3]. Indeed, this ZIK-V manifestation has peculiar characteristics that led to speculation about a possible different pathogenesis compared to classical GBS: a) they seem to arise 5 to 10 days after infection and have higher morbidity, more frequent cranial neuropathies and concurrent immune-mediated disorders such as thrombocytopenic purpura [4]; b) anti-glycolipids antibodies typically involved in cross-reactive mechanisms are not common [5]; c) there is a predominant involvement of distal nerve segments [3], where the blood–nerve barrier is lacking.
The mechanisms underlying a para-infectious pathogenesis have yet to be established, but in some predisposed patients ZIKV might generate an aberrant immune response that, in turn, causes GBS; in particular, it has been proposed that specific ZIKV-peptides might not only cross-react, but also induce a cellular immune reaction through antigen- presenting cells activation of T-lymphocytes [6].
Likewise, the timing of neurological signs in our case may be too rapid to imply a heterologous immune reaction to a first viral exposure and it might suggest other pathogenic mechanisms, such as direct viral damage (i.e. CMV and VZV neuritis) or acute dysimmune processes that arise as a part of systemic inflammatory response (which has been presumed on the basis of lung involvement in itself). The growing number of extra-pulmonary manifestations of COVID-19, the immunological nature of GBS itself, the absence of SARS-CoV-2 in the CSF and the delayed onset of paralysis in our patient might theoretically support the second hypothesis rather than a viral effect.
Specific serological assays were not available at the time of her examination, but the hypothesis of neurological manifestations of COVID-19 is supported by the evidence of neurotropic and neuroinvasive characteristics of coronaviruses in both mice and humans [7]; moreover, other strains of human coronaviruses have already been involved with peripheral nervous system manifestations [8-9] and with pediatric cases of GBS [10-11].
Along with dedicated research, it will be crucial to monitor the incidence of GBS in the coming months, as a concurrent increase in cases during COVID-19 outbreak would further support a possible causal relation1.