COVID-19 Infection Presenting as Myalgia, Abnormal Liver Function Tests and the Guillain-Barre Syndrome

The severe acute respiratory syndrome coronavirus 2 infection typically presents with respiratory symptoms. Additionally, there are a number of less frequent neurological manifestations of infection with the coronavirus disease 2019 (COVID-19) with case reports suggesting an association with the Guillain-Barre syndrome. Most patients present with the typical upper respiratory symptoms in association with these neurological symptoms. We present a case of an unvaccinated gentleman with none of the typical respiratory symptoms of COVID-19 who presented with the Guillain Barre syndrome and myalgia. His symptoms settled following treatment with intravenous immunoglobulins. This case highlights the importance of testing for COVID-19 in patients without typical symptoms but who present with neurological illness and supports the use of intravenous immunoglobulin therapy.


Introduction
Following an outbreak of a contagious lower respiratory tract infection in Wuhan, China at the end of 2019, The World Health Organization (WHO) subsequently declared this a Public Health Emergency of International Concern [1]. This virus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was a novel form of coronavirus belonging to the genus Betacoronavirus and subgenus Sarbecovirus [2]. This disease has resulted in a worldwide increase in hospitalizations for pneumonia with multiorgan disease  [3].
The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. SARS-CoV-2 transmission is primarily by direct person-to-person transmission, mainly through close-range contact via respiratory particles which cause infection if these particles are inhaled or make direct contact with the mucous membranes. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing. The infectivity is the greatest in the early stages of infection, starting just prior to the development of symptoms. Transmission after 7 to 10 days of illness is unlikely, although prolonged viral shedding after symptom resolution may continue.

Case Report
A 71-year-old gentleman who had not been vaccinated against COVID-19, presented at the emergency department on the 26 th of January 2022 with a 4-day history progressive leg weakness, and muscle pain in his back, anterior and lateral thighs. The pain in his thighs meant it was uncomfortable for him to sleep lying on either side and as such he was sleeping only on his back. He was still able to walk at the time. The patient then went home because he was concerned about looking after his pets. He came back to the hospital on the 29 th of January because he was unable to pass urine, and had not opened his bowels for 4 days.
Additionally, his weakness had continued to progress and he now needed a Zimmer frame to mobilize and that with difficulty. He agreed to be admitted on that day. An incidental COVID-19 test taken at his initial presentation, was reported as being positive.
He denied a cough, or sputum production, with no nasal stuffiness, dyspnea, orthopnea or paroxysmal nocturnal dyspnea. Additionally, did not report a temperature or chills. He had no chest pain or palpitations. He has had no diarrhea, and had not lost his sense of taste or smell, with no other ear, nose and throat symptoms. Additionally, he had no skin rash or joint pains and denied abdominal pain, chest pain, palpitations or edema.
On examination, his temperature was 36.4 degrees Celsius. He was a thin man who weighed 57 kg. He was not pale, jaundiced or cyanosed with no pedal edema or clubbing. His pulse was regular at 80 per minute. His blood pressure 149/88, heart sounds 1 and 2 were audible with no murmurs. His respiratory rate was 20 per minute. His oxygen saturation was 98% on room air. His chest was clinically clear. His liver, spleen and kidneys were not palpable. Bowel sounds were present and normal.
His muscle tone and bulk were normal and neurological examination disclosed symmetric weakness (Medical Research Council grade 4/5) and areflexia in both legs and feet. Sensation to light touch, vibration, pinprick and proprioception were normal.
He worked as a clam digger and admitted to drinking 1 -2 alcoholic beverages most days and did not smoke cigarettes. He was divorced and had a son and a daughter. His past medical history included a bilateral inguinal herniorrhaphy a left hydrocelectomy and hemorrhoids.

Laboratory Results
His laboratory results were reported as follows: Haemoglobin 134 g/l, white cell count 6.4 × 10 9 /l, with a low lymphocyte count at 0.9 × 10 9 /l and a platelet count of 231 × 10 9 /l. Renal function tests were unremarkable as were liver function tests except for raised transaminases (see Table 1). Sodium, potassium, calcium, phosphate and magnesium levels were    Table 1. This patient received treatment with a total of 2 g/kg of intravenous immunoglobulin spread over the next 3 days.
Five days after his initial admission, he reported that his thigh pain had resolved. He did not develop any sensory deficits during his admission. He initially required the help of two nurses to stand on admission but by day 6 he was standing independently but mobilizing with the help of a Zimmer frame for support. His urinary catheter was removed on day 7 of his admission and he passed urine normally and he was discharged home. As per current local guidelines, a repeat COVID-19 pcr study was not carried out at discharge. Furthermore, the COVID-19 genotype was not determined in this patient.
He was seen for a review appointment 2 weeks after discharge and by that

Discussion
SARS-CoV-2 infection appears to be associated with neurological and neuropsychiatric illness. Five major categories of illness have been identified including: 1) encephalopathies with delirium/psychosis and no distinct MRI or CSF abnormalities, 2) inflammatory CNS syndromes including encephalitis, acute disseminated encephalomyelitis 3) ischemic strokes associated with a pro-thrombotic state, 4) peripheral neurological disorders including the Guillain-Barré syndrome, and 5) miscellaneous central disorders who did not fit these categories. Some cases, respond to immunotherapies including steroids or intravenous immunoglobulins [7]. COVID-19 mRNA was not typically found in the cerebrospinal fluid when tested but one study from the Sudan, reported the CSF being positive for COVID-19 [8]. cases, and CSF SARS-CoV-2 RNA was absent in all tested cases. More than 70% of patients showed a good prognosis, mostly after treatment with intravenous immunoglobulin [9].
There has been a case report of delayed onset, acute demyelinating neuropathy in a 46-year-old man 53 days after COVID-19 pneumonitis. He presented with bilateral leg pain and loss of sensation in his feet followed by a rapidly progressive lower motor neuron weakness involving all limbs, face and respiratory muscles, needing ventilatory support. The cerebrospinal fluid examination showed albuminocytologic dissociation and nerve conduction studies supported the diagnosis of an acute inflammatory demyelinating polyradiculoneuropathy. The authors conclude that this case might indicate that the Gullain Barre syndrome may be part of the "long COVID-19 syndrome" [10]. The study concluded that although it was not possible to entirely rule out the possibility of a link, there was no epidemiological data to prove this. The overall reduction in GBS incidence during the pandemic, was thought to be due to the influence of lockdown measures reducing transmission of known GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses [11].
Guillain Barre syndrome has been reported after COVID-19 vaccination, including the Astra-Zeneca [12], Pfizer [13] and Moderna [14] vaccines. However, compared to a worldwide typical incidence of 1.1/100,000, an analysis of a co- Nerve conduction studies (day 5) showed delayed distal latencies and absent F waves in early course, supporting demyelinating neuropathy. She received treatment with intravenous immunoglobulin and the antiviral drugs arbidol, lopinavir, and ritonavir and at discharge on day 30, had normal muscle strength in both arms and legs and return of tendon reflexes in both legs and feet. The SARS-CoV-2 virus has been isolated from the CSF raising the possibility that it may have neuroinvasive potential [17]. Typically, antiganglioside antibo-dy tests were negative supporting the view that non-immune abnormalities such as hyperinflammation following cytokine storms and microvascular disorders due to vascular endothelial damage may lead to neurological symptoms in patients with SARS-CoV-2 infection [19].
Myalgia myositis and rhabdomyolysis have been described in association with COVID-19 infection. Few patients had muscle weakness and elevated creatine kinase levels along with elevated levels of acute-phase reactants. Typically, patients with myositis/rhabdomyolysis had severe respiratory complications. A handful of patients with myasthenia gravis had and exacerbation of their disease after acquiring COVID-19 disease. Most of these patients recovered with either intravenous immunoglobulins or steroids [20].

Conclusions
There is increasing evidence of neurological manifestations of COVID-19 infection. The Guillain Barre Syndrome is increasingly being recognized as a presenting feature of infection, and may occur during otherwise asymptomatic infection. However, the individual risk for GBS remains small.
The association between COVID-19 and GBS is still uncertain, but a high index of suspicion of possible infection should be assumed during this pandemic. Thorough and well-designed GBS detection studies with accurate case definition and confirmation are needed to complement the increasing case reports of an association between COVID-19 and GBS. This case adds support to the potential value of the use of intravenous immunoglobulins in the treatment of GBS associated with COVID-19.

Conflicts of Interest
The author declares no conflicts of interest regarding the publication of this paper.