Discussion

Neurological sequelae have been estimated to occur in 36.4 per cent of Covid-19 cases.^{Reference Mao, Jin, Wang, Hu, Chen and He5} Central nervous diseases such as debilitating encephalopathies and ischaemic insults have been described as complications of initial Covid-19 pneumonia.^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3,Reference Orsucci, Caldarazzo Ienco, Nocita, Napolitano and Vista9} However, a study by Mao et al. recognised peripheral nerve involvement, with hypogeusia (82 per cent) and hyposmia (86 per cent) classified as common symptoms of SARS-CoV-2 infection.^{Reference Mao, Jin, Wang, Hu, Chen and He5,Reference Wu, Xu, Chen, Duan, Hashimoto and Yang10} Ellul et al. estimated the number of Covid-19 associated peripheral nervous system diseases to be between 2047 and 7737, based on extrapolations from previous severe acute respiratory syndrome and Middle East respiratory syndrome data.^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3}

Furthermore, polyneuropathies including Guillain–Barré syndrome, Miller Fisher syndrome and polyneuritis cranialis have also been reported in infected SARS-CoV-2 patients.^{Reference Toscano, Palmerini, Ravaglia, Ruiz, Invernizzi and Cuzzoni11–Reference Kopscik, Giourgas and Presley14} Two patients experienced symptoms of Guillain–Barré syndrome as the initial presentation of SARS-CoV-2, and had documented fever 7 days later.^{Reference Mao, Jin, Wang, Hu, Chen and He5}

At the time of writing, only two case reports have described a likely correlation between SARS-CoV-2 and isolated cranial neuropathies, specifically VIIth cranial nerve palsy.^{Reference Wan, Cao, Fang, Wang and Huang15,Reference Goh, Beh, Makmur, Somani and Chan16} Both cases reported post-auricular pain as a preceding symptom, and this symptom was recognised in 20 per cent of our cohort. Interestingly, one of the SARS-CoV-2 positive patients experienced a succession of viral-associated symptoms: lethargy and anosmia, followed by labyrinthitis.

The aforementioned polyneuropathies and VIIth cranial nerve palsy are associated with infectious aetiologies.^{Reference Zhang, Xu, Luo, Wu, Zhao and Li17} Whilst studies so far have not shown SARS-CoV-2 nor its family members to be highly neurovirulent,^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3} a number of mechanisms have been postulated.^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3,Reference Li, Liu, Yang, Han, Mi and Li4,Reference Wu, Xu, Chen, Duan, Hashimoto and Yang10} Deficits in taste and smell have been seen to occur in isolation of other coryzal symptoms, suggesting possible olfactory bulb involvement and central nervous system invasion.^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3,Reference Wu, Xu, Chen, Duan, Hashimoto and Yang10,Reference Goh, Beh, Makmur, Somani and Chan16}

However, the virus’ absence in cerebrospinal fluid in a number of Covid-19 cases leads to a different proposition.^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3,Reference Gutiérrez-Ortiz, Méndez, Rodrigo-Rey, San Pedro-Murillo, Bermejo-Guerrero and Gordo-Mañas12,Reference Goh, Beh, Makmur, Somani and Chan16} The binding of SARS-CoV-2 to angiotensin-converting enzyme 2 (ACE2) may trigger the body's innate immunological systems to cause elevated pro-inflammatory cytokines and, as a result, neuronal damage.^{Reference Ellul, Benjamin, Singh, Lant, Michael and Kneen3,Reference Li, Liu, Yang, Han, Mi and Li4,Reference Wu, Xu, Chen, Duan, Hashimoto and Yang10} ACE2 is also found in the nervous system, therefore implicating a possibly more direct route to nerve injury.^{Reference Goh, Beh, Makmur, Somani and Chan16}

Inflammation-induced demyelination is also a widely supported cause of Bell's palsy, wherein a viral-induced autoimmune reaction results in peripheral demyelination of the cranial nerve. There is a similar high neutrophil-to-leukocyte ratio in Bell's palsy when compared to acute demyelinating diseases (such as Guillain–Barré syndrome); however, the pathways causing this remain unclear.^{Reference Zhang, Xu, Luo, Wu, Zhao and Li17}

The significant difference in VIIth cranial nerve palsy cases between the two years in this study suggests a potentially coronavirus-driven increase in palsies.

It is understandably difficult to draw definitive conclusions from differences in the Covid-19 incidences of our cohort and Liverpool's population, given the small patient sample size. However, whilst only 57 per cent of patients (17 out of 30) underwent coronavirus testing, 12 per cent of results (2 out of 17 patients) were positive, which may prove to be an undervaluation if the rest of the cohort underwent coronavirus testing.

Interestingly, Tseng et al. showed an association between anxiety disorders and VIIth cranial nerve palsy.^{Reference Tseng, Hu, Liu, Yang, Shen and Tsai18} Given the current Covid-19 climate, it may be hypothesised that increased anxiety levels may predispose to VIIth cranial nerve palsies.

With respect to treatment, Wan et al. administered prednisolone and the antivirals Arbidol® and ribavirin to their coronavirus-related VIIth cranial nerve palsy patient, who subsequently showed complete recovery.^{Reference Wan, Cao, Fang, Wang and Huang15} Conversely, another case of coronavirus-related palsy treated with lopinavir, ritonavir and prednisolone, reported by Goh et al., did not display any significant improvement, despite lowering the patient's viral load.^{Reference Goh, Beh, Makmur, Somani and Chan16} In our cohort, both patients who tested positive for SARS-CoV-2 recovered with solely prednisolone regimens. Antiviral therapy showed indifferent results, with only three of the five patients who were prescribed antivirals and followed up exhibiting a full recovery.