Discussion:
We are learning to understand the COVID-19 disease, an
emerging infection that resulted in a global pandemic. Initially,
respiratory symptoms are most distinctively seen in COVID-19 patients.
It is believed that pro-inflammatory cytokine release, known as
‘cytokine storm,’ causes pulmonary damage, and it is the likely
mechanism of CNS damage. ACE2 is the functional receptor for the
SARS-CoV-2 virus, present in multiple organs such as the lungs, heart,
nervous system, skeletal muscles, blood vessels, kidney, liver, and
gastrointestinal tract. The ACE2 receptor is found remarkably in the
epithelial lining of lung alveoli, enterocytes of the small intestine,
the endothelial lining of arteries and veins, and arterial smooth
muscles of all organs.4 Hence, COVID-19 can affect any
of the organs, as mentioned above. SARS-CoV-2 enters the CNS through
either a hematogenous or retrograde neuronal route; the neural invasion
mechanism is mainly through the cribriform plate, olfactory nerve,
thalamus brainstem. Thus, resulting in the suppression of central
cardiorespiratory drive.5 Mao et al., in a study in
Wuhan published in April 2020, mentioned that the neurological
manifestations are seen in critically ill patients.6Later, it is noticed that many patients with few or no symptoms of
COVID-19 disease also had neurological symptoms.7Further, Mao et al. classified neurological manifestations as dizziness,
headache, impaired consciousness, ataxia, seizure, and acute
cerebrovascular disease into central nervous system manifestations.
Nerve pain, taste, smell, and vision impairment into peripheral nervous
system manifestations and skeletal muscular injury
manifestations.6
Our patient presented with features of peripheral nerve
involvement (anosmia and dysgeusia), cranial nerve involvement
(hemifacial spasms and vestibular neuritis), and Raynaud’s phenomenon.
Peri- and post-infectious anosmia and dysgeusia could be secondary to
olfactory nerve lesion or apparatus damage from viral infection. The
majority of patients presented at the same time or a few days after the
onset of other COVID-19 symptoms.8 Hemifacial spasm is
a neuromuscular movement disorder with slight intermittent contractions
or twitching of the muscles innervated by the facial nerve (cranial
nerve VII). Though twitching is irregular initially, it may be severe,
more persistent, and can spread to the muscles of facial expression in
the following months. Sometimes, a mild peripheral weakness can develop.
The spasms are due to compression of the facial nerve by the artery at
the root exit of the brainstem. The clinical features are essential in
diagnosing the disease; electromyography and magnetic resonance imaging
(MRI) are additional diagnostic modalities to determine the underlying
cause.9 A case report by Hutchins et al. described the
association of bilateral facial paralysis with paresthesia, a subtype of
Guillain- Barre syndrome, and COVID-19.10 Few studies
describe facial nerve involvement, causing Bell’s palsy but relatively
do not know much about the hemifacial spasms in COVID-19.
Acute vestibular neuritis (VN), or peripheral vestibulopathy
(PVP), is defined as a lesion of the eighth cranial nerve’s vestibular
component without auditory deficits. It is a clinical entity with the
features of vertigo or dizziness along with nausea or vomiting, gait
instability, head motion intolerance, and nystagmus, which is developed
over minutes or hours. The most common cause is the reactivation of
latent herpes simplex virus, especially herpes simplex virus type 1
(HSV-1).11 But a case report by Malayala et al.
mentioned that COVID-19 infection could cause vestibular neuritis in
susceptible populations.12 The possible source of
vestibular neuritis in our patient is post-viral inflammation of the
vestibular nerve, probably due to HSV-1 or COVID-19 infection.
Considering the pandemic, the cause of VN is perhaps due to COVID-19
infection, given that VN’s features were seen after a week of negative
COVID-19 test. As pathophysiology is uncertain in most cases,
symptomatic treatment with antiemetics, antihistamines, anticholinergic
agents, antidopaminergic agents, and benzodiazepines are
given.13 Sometimes, methylprednisolone shows
significant improvement of peripheral vestibular function recovery in
severe cases. 14 Resumption of regular activity and
vestibular rehabilitation with Cawthorne and Cooksey exercises promotes
central vestibular compensation.15
COVID-19 has also been associated with various cutaneous
manifestations like a morbilliform rash, urticaria, vesicular eruptions,
acral lesions, petechiae, chilblains, Livedo racemosa, and distal
necrosis.3,16 The possible mechanisms for cutaneous
manifestations are the lymphocytic vasculitis induced by blood immune
complexes activated by cytokines due to viral particles in the cutaneous
blood vessels in patients with COVID-19.17 A few case
reports noted that cutaneous findings are present before developing
respiratory symptoms. In contrast, a few case reports found that these
findings are seen several days after the onset of
symptoms.16 Our patient presented with Raynaud’s
phenomenon (RP) during the disease and urticarial rash several weeks
later despite no previous history. Kolivras et al. described the first
case of COVID-19 induced chilblains due to the delayed expression of the
IFN-inducible genes, further exacerbating
hypercytokinemia.18 Chilblains and RP are related to
circulation but do not necessarily mean to have both. Chilblains are an
inflammatory skin reaction to an abnormal vascular response to cold.
They present as tender, pruritic, red lesions on the dorsal aspect of
fingers or toes. 19 In contrast, RP is the triphasic
color change with initial pallor, followed by cyanosis and erythema due
to abnormal vasoconstriction of the digital arterioles when exposed to
cold. RP’s diagnosis is mainly made with history, and physical
examination mainly affects hands, and the thumb is often spared. RP is
primarily associated with systemic lupus erythematosus and CREST
(Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly,
and Telangiectasia) syndrome. Hence, the autoantibodies and nail fold
capillary microscopy together give a clue to the diagnosis. Most of the
patients with RP will respond well with general measures like smoking
cessation, avoidance of cold exposure, repeated trauma, and
vasoconstricting drugs. Few patients who do not respond to general
measures will require pharmacological treatment that includes a calcium
channel blocker, losartan, an angiotensin II receptor
blocker.20
Our case report mentioned the neurological and cutaneous manifestations
in a patient with COVID-19 with an excellent prognosis. To our
knowledge, this is the first case report of COVID-19 induced hemifacial
spasms and Raynaud’s phenomenon. Until further validation by other
studies, we would like to alert the clinicians to various disease
presentations in COVID-19, who are immediately tested and treated.
Respiratory symptoms remain the hallmark of early identification and
management of COVID-19; the treatment should not be delayed while
keeping in mind the other manifestations.