Background
Coronavirus disease-2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a single-stranded positive linear RNA beta coronavirus with an envelope and spike proteins on the outer surface [1,2]. COVID-19 symptoms can include fever, cough, and shortness of breath, along with several nervous system presentations, such as hypogeusia, hyposmia, dizziness, and headache [1-5]. The degree of symptom severity depends on various factors, including age and comorbidities that have weakened the immune system. Extreme symptom severity has led to death.
Guillain-Barré syndrome (GBS) is a demyelinating autoimmune disorder in which the body’s immune system attacks the myelin sheath of the peripheral nervous system [6]. It commonly presents a few days after upper respiratory tract infections or gastroenteritis. The most common presentation is ascending paralysis starting from the lower limbs which slowly progresses to involve the breathing muscles causing respiratory failure in a matter of a few weeks only [2,7]. Other symptoms include weakness in coordination, hyporeflexia, weakness in eye muscles, and autonomic dysfunction affecting the heart rate and blood pressure [7]. Some pathogens associated with GBS are Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Zika virus, and Mycoplasma pneumoniae [4,5,7].
The association between COVID-19 and GBS is novel, and the mechanism of action is still being investigated with a variety of theories. Regardless of the mechanisms involved, patients with a recent history of COVID-19 have developed GBS. The case report presented herein contributes to the vital data collection necessary to help the scientific community further understand the epidemiology and prognosis of GBS sequelae of COVID-19.
Case Presentation
An 83-year-old Caucasian woman with a past medical history significant for chronic atrial fibrillation, dyslipidemia, and hypertension presented to the emergency department (ED) with a low-grade fever, cough, extreme fatigue, and weakness for 2 weeks. Due to her symptoms, rapid SARS-CoV-2 testing was performed and results came back positive. In the ED, her temperature was 99.9 F, respiration rate was 20 per minute, and oxygen saturation was 95%. WBC count was 5.16 k/µl, hemoglobin was 15.1 g/dl, and troponin level was elevated at 20 and 24 ng/l. Electrocardiogram (ECG) and chest X-ray were also done which were consistent with atrial fibrillation and early bilateral interstitial infiltrates. The patient was admitted and treated with intravenous (IV) and oral fluids with minerals, multivitamin supplements, pain, and pyrexia management. IV anticoagulants and antiviral medications were not given as the patient was not hypoxemic. Post-acute care management of the COVID-19 infection, the patient was sent to the skilled nursing facility for rehabilitation and medical management. One week after her transfer, the patient developed new symptoms of severe bilateral lower extremity (LE) pain, numbness, tingling, and difficulty walking. Neurologic examination revealed decreased sensations, 0/5 strength, and diffuse areflexia in bilateral lower limbs. Computed tomography and ultrasound of the bilateral LEs were performed and no significant abnormalities were seen. Due to her symptoms concerning GBS, electromyography and nerve conduction velocity (EMG/NCV) study were performed which showed abnormalities highly suggestive of an acute inflammatory demyelinating polyneuropathy (AIDP) process/GBS (Figure 1). The patient also underwent a fluoroscopy-guided lumbar puncture which showed pink cerebrospinal fluid (CSF) with an RBC count of 1,106, no WBC, glucose level of 50 mg/dl, and elevated protein of 64 mg/dl consistent with albuminocytologic dissociation.
EMG/NCV study of the patient demonstrating abnormal partial and complete conduction block in multiple motor nerves and sparing of the sural nerves highly suggestive of an AIDP/GBS. Lat Mall: lateral malleolus, EDB: extensor digitorum brevis, AH: abductor hallucis, MUAP: motor unit potential, IA: insertional activity Fib: fibrillation potentials, PSW: positive sharp waves, Fase: fascination potential, Dur: duration, Amp: amplitude, PPP: polyphasic potentials, Rectum: recruitment pattern.
The patient was started on intravenous immune globulin (IVIG) 0.5 gram/kg for 5 days and continued with physical and occupational therapy (PT/OT). After 5 days of IVIG treatment, the patient continued to have numbness and weakness in her LEs. Subsequent magnetic resonance imaging of the brain and the entire spine were unremarkable. Due to no clinical improvement in her symptoms after a course of IVIG treatment, plasmapheresis was initiated. After a total of three plasmapheresis treatments, the patient’s symptoms have subsided significantly with improved sensations and strength in her LEs. Following improvement, the patient was sent to the acute rehabilitation unit for further PT/OT and performed gradual improvement of her motor strength.
Discussion
In this study, we report AIDP in a patient recently diagnosed with COVID-19. In AIDP, acute demyelination causes classic ascending motor paralysis and sensory abnormalities, resulting in death if the diaphragmatic muscles are also affected [4]. The diagnosis of GBS starts with the detailed history of infection onset and resolution in the patient and constitutes findings from spinal fluid and neurophysiology. The characteristic findings in CSF include a protein level greater than 0.55 g/l and fewer than 10 WBCs commonly known as “albuminocytological dissociation” [6]. EMG/NCV testing could be further used to exclude other causes of muscle weakness from GBS [7]. These diagnostic techniques used in our patient showed results that are highly suggestive of AIDP/GBS. The management of GBS is mainly immunotherapy treatments with plasmapheresis and IVIG [5]. Both treatments work to neutralize the harmful antibodies attacking the peripheral nervous system and are effective modalities. Our patient was treated with both therapies, unfortunately, with her aging and immunocompromised nature, the IVIG did not work efficiently. However subsequent plasmapheresis therapy showed adequate improvement in her symptoms.
COVID-19 infection stimulates the inflammatory cytokines causing endothelial cell injury resulting in acute respiratory distress syndrome as the major cause of death in many patients [7]. However, this virus has been rapid in affecting almost every other body system including the nervous system causing initial neurological symptoms as anosmia and ageusia [6]. There have been many cases reported of COVID-19 association with GBS having a wide spectrum of etiologies [7]. The mechanism of action is still unclear. The explanation of other viral and bacterial causes of GBS is post-infectious molecular mimicry and cross-reactivity [1-7]. The view applied here would be that SARS-CoV-2 has certain gangliosides on its surface, which resemble gangliosides found in the peripheral nervous system [6]. The host body inadvertently attacks the gangliosides on the peripheral nervous system when it mounts an immune response to the SARS-CoV-2 surface ganglioside [6]. A recent study by Keddie et al. has partially challenged this theory by showing no significant homology between the SARS-CoV-2 and human linear protein structures; however, the same study suggested viral protein modifications within host cells leading to surface protein homology [8]. In our patient, the common respiratory flu-like illness that turned out positive for COVID-19 further led to having triggered GBS within a few weeks.
It is an interesting finding that many patients affected with COVID-19 were found to have elevated troponin levels [9]. This finding has a direct association with cardiac injury thereby highly associated with mortality rates in COVID-19 patients [9,10]. The theory relies on the role of ACE2, the binding receptor for SARS-CoV-2 cellular entry [9]. Angiotensin-converting enzyme 2 (ACE2) is highly expressed in cardiac pericytes and pulmonary cells serving a protective role in their pathophysiology [9]. In addition to using ACE2 as an initial entry point, the virus also downregulates its expression resulting in reduced conversion of angiotensin II (Ang-II) to angiotensin 1 (Ang-1) [10]. This leads to detrimental cardiac injury by affecting the renin-angiotensin-aldosterone system leading to complications such as myocarditis, congestive heart failure, and even myocardial infarction in COVID-19 patients [10]. Similarly, in our patient, elevated troponin levels were found which could have a role in the rapid weakness and deterioration of her condition. It could also be a possible reason that the cardiac injury made her immune system too weak to respond to the initial treatment of GBS leading to its failure.
Conclusion
The acute phase of COVID-19 infection usually affects the respiratory system and cardiovascular system as seen in our patient. The case report also indicates that GBS is considered as a neurological complication seen in convalescent phase or post recovery phase of an acute COVID-19 infection. With the increasing correlation between COVID-19 and GBS, clinicians must be aware of and include GBS in the differential diagnosis when a patient with history of COVID-19 infection presents with neurological symptoms. It is also essential for clinicians to diagnose GBS early and treat it properly, especially in elderly patients and patients with comorbidities, to improve the chance of successful recovery in view of potential complications of acute respiratory and cardiovascular failures.
What is new?
The association between COVID-19 infection and Guillain-Barre syndrome has been growing since the outbreak in January 2020. More severe presentation and prolonged recovery are seen in elderly/immunocompromised patients; therefore, prevention and treatment in a timely manner are crucial. Clinicians should be aware of neurological complications of an acute COVID-19 infection and include GBS in the differential diagnoses.