FormalPara Key Summary Points

Reports on Guillain–Barré syndrome (GBS) Post-COVID-19 vaccination associated with COVID-19-induced acute respiratory distress syndrome (ARDS) are still limited.

COVID-19-induced ARDS can happen in subject who had COVID-19 vaccine shot after 2 weeks.

Accurate diagnosis of ARDS due to COVID-19 to differentiate with acute respiratory failure due to GBS is very important for starting the appropriate treatment.

Therapeutic plasma exchange is the first-choice treatment in combination with conventional therapy in patients with GBS due to vaccine and concomitant ARDS due to COVID-19.

Introduction

Vaccination is the most important tool to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and prevent coronavirus disease 2019 (COVID-19) severity. During the outbreak of the COVID-19 pandemic, vaccines from different manufacturers were developed and administered to people worldwide. Among them, Vero Cell, made by the Beijing Institute of Biological Products Co. Ltd (China), has been accepted by the World Health Organization (WHO) for use in emergency situations in more than 60 countries [1]. In the United States, the Food and Drug Administration (FDA) authorized two World Traders Inc. for the emergency use of the inactivated COVID-19 vaccine Sinopharm (Vero Cell) in August 2021 [2].

Although many studies have demonstrated the post-vaccination adverse reactions of different vaccines, only a few reports have focused on the Sinopharm COVID-19 vaccine (Vero Cell) [3,4,5,6,7]. The side effects of this vaccine appeared to be mild in a previous study: more than 15% of vaccinated people reported any symptoms after their first vaccination dose, while the majority had mild and predictable side effects after the second dose, and none had severe side effects or required hospitalization [8,9,10]. The WHO announced that most side effects of the Sinopharm COVID-19 vaccine were mild to moderate, including headache, fatigue, and injection site reactions [1]]. However, in addition to mild adverse reactions, severe adverse reactions to the Sinopharm COVID-19 vaccine (Vero Cell) have been reported [11].

Guillain–Barré syndrome (GBS) has been reported to be associated with COVID-19 vaccination; however, there are few comprehensive reports regarding this rare adverse event. A multi-institutional study and systematic review of the literature revealed that GBS associated with COVID-19 vaccination was presented mostly in the classic form and in the acute inflammatory demyelinating polyneuropathy subtype within 2 weeks of vaccine administration [12]. Before the COVID-19 pandemic, this immune-mediated polyradiculoneuropathy syndrome (GBS) had an incidence of less than 2% worldwide, with a 5% mortality rate [13].

In Vietnam, during the outbreak of the COVID-10 pandemic, the government strategy entitled “One Million Vaccination Campaign” was deployed in Binh Duong city in the first 2 weeks of September 2021. This city had the second highest number of patients with COVID-19 during the fourth pandemic wave of this disease in Vietnam [14, 15]. During this vaccination campaign, more than 1 million doses of Vero Cell were administered to the residents of Binh Duong at that time.

In this case report, we present a patient who was hospitalized due to progression of GBS that occurred 10 days after his first Vero Cell vaccination dose administration. Unfortunately, during hospitalization, the patient contracted COVID-19 from the visits of his family members and developed acute respiratory distress syndrome (ARDS), which required transfer to the COVID-19 intensive care unit (ICU) of Phu Chanh COVID-19 Hospital in Binh Duong city. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and therapeutic plasma exchange (TPE). He was discharged from the COVID-19 hospital after 7 weeks and was followed-up regularly. Currently, the patient has a good health status and works in the same job as before contracting the illness.

Case Description

A 22-year-old man was admitted to the Department of Neurology of Binh Duong General Hospital with progressive bilateral extremity weakness in September, 2021. The weakness began in the lower extremities and then progressed to the upper extremities in the course of 2 weeks after COVID-19 vaccination. The patient had no fever, cough, or other respiratory symptoms prior to admission. He received one dose (first dose of COVID-19 inactivated vaccine (Vero Cell) 2 weeks prior and had no previous history of pulmonary or neurological disorders or abnormalities. The RT-PCR test result for COVID-19 was negative before vaccination, at admission, and 2 days later.

On physical examination, the patient was conscious and responded poorly to the verbal stimuli. His respiratory rate was 24 breaths/min, blood pressure was 120/80 mmHg, heart rate was 80 beats/min, and SpO2 was 98% (with ambient air). Lung sounds were coarse on auscultation. Muscular strength was 0/5 bilaterally in the lower extremities and 3/5 in the upper extremities according to the Medical Research Council (MRC) scale, and no other neurological deficit was found. The patient was diagnosed with GBS due to Vero Cell vaccination and was followed-up at the Neurology Department with supportive therapy (day 1). Other diagnoses, such as compressive myelopathy, transverse myelitis, or acute myelitis, were excluded by a multidisciplinary specialist staff.

Unfortunately, during hospitalization, the patient contracted COVID-19, confirmed by the COVID-19 antigen test after having symptoms, after being visited by a family member who was positive for COVID-19. The patient was also positive for nasopharyngeal SARS-CoV-2 by RT-PCR on the days after the family visit. Cough, fever, sore throat, and dyspnea developed after 2 days with an SpO2 of 94% (ambient air). He was diagnosed with GBS due to vaccination and contracted COVID-19 pneumonia. His treatment included oxygen (3 l/min through cannula), intravenous corticosteroids, antibiotics for the prevention of superinfection, and subcutaneous heparin (enoxaparin).

Forty-eight hours later (day 3), the patient developed peripheral facial paralysis, failed to chew and swallow effectively, and required tube feeding. From days 4 to 6, his cough worsened, sputum increased, and shortness of breath progressively developed. The SpO2 level dropped to 88% and then to 83% while the patient received oxygen through a non-rebreather mask (15 l/min). Chest radiography showed alveolar infiltration (Fig. 1); laboratory studies demonstrated increased fibrinogen, ferritin, and lactate dehydrogenase (LDH) levels; and his cerebrospinal fluid (CSF) showed cytoalbuminologic dissociation (Table 1). Cardiac ultrasound revealed an ejection fraction (EF) of 66% with no regional wall motion abnormalities; the maximum and minimum inferior vena cava were 10 and 4 mm, respectively.

Fig. 1
figure 1

Chest X-ray showing alveolar infiltration

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Table 1 Results of laboratory tests during hospitalized stay of the reported patient
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The patient was transferred to the intensive ICU of Phu Chanh COVID-19 Hospital of Binh Duong General Hospital and was then intubated for invasive mechanical ventilation (IMV) due to acute respiratory distress syndrome (ARDS): VT = 320 ml, f = 18/min, i/e = 1/1.7, positive end-expiratory pressure (PEEP) = 12 cmH2O, and FiO2 = 90%. Antibiotics were changed to prevent IMV-induced nosocomial pneumonia using cefadroxil and levofloxacin; corticosteroid administration was also initiated (dexamethasone 6.6 mg/day). The patient was also administered five cycles of TPE with 5% albumin replacement on day 11 due to progressive severity.

The patient’s respiratory and neurological symptoms improved by day 28; thus, he was weaned off mechanical ventilation and administered oxygen through the cannula. He was cared for continuously in the hospital and discharged on day 42 (Fig. 1). After discharge from the hospital, the patient was followed up in the outpatient department every 2 months. At 6 months after hospital discharge, his muscular strength was 5/5 bilaterally in the lower and upper extremities according to the MRC scale; no sequelae of peripheral facial paralysis and other neurological deficits were found. Currently, the patient has a good health status and works in a shoe factory in his hometown.

Written informed consent was obtained from the patients’ parents to publish clinical details.

Discussion

GBS is a neurological disorder that can occur after immunization or viral infection [16,17,18]. In this case report, we presented a patient with progressive paralysis from the lower to upper limbs that occurred after receiving the first dose of COVID-19 inactivated vaccine (Vero Cell, Sinopharm). He was admitted to the hospital in the second week of symptom onset with upper and lower limb weakness and no respiratory symptoms. The patient tested negative for SARS-CoV-2, which was screened during hospitalization. Therefore, GBS diagnosis due to the vaccine was more likely at the time of admission. GBS was confirmed by cytoalbuminologic dissociation in cerebrospinal fluid analysis. In this case report, other different diagnosis such as compressive myelopathy, transverse myelitis, acute myelitis, or GBS due to other causes were excluded by a multidisciplinary specialist staff based on laboratory testing and MRI. In particular, the patient had no neurogenic urinary or fecal incontinence, or any history of spinal trauma. The results of serologic testing for Campylobacter jejuni and Cytomegalovirus were negatives. However, Binh Duong General Hospital Lab could not do ganglioside antibodies at the moment of 4th wave of COVID-19 pandemic for this case report.

CSF was done at day 3 after hospitalization. This delay was due to at that moment all the healthcare resources were mobilized for COVID-19 patient care. Especially, this case report was happened at the highest peak of 4th COVID-19 pandemic in Binh Duong Province, the area of Vietnam with the second-highest prevalence of COVID-19 infection and death. Unfortunately, for this reason, electroneurography could not be done when the patient was hospitalized in ICU of COVID-19 hospital at that moment.

However, the reported patient contracted COVID-19 during his family’s visit to the hospital, confirmed by respiratory symptoms and positive COVID-19 PCR test results. The patient’s respiratory symptoms worsened in the first week after admission. Laboratory tests at that time showed increased levels of inflammatory markers, such as LDH, ferritin, and fibrinogen, associated with bilateral pulmonary infiltration on chest radiography and acute respiratory failure. Hence, his medical history and clinical status were appropriate for the diagnosis of ARDS due to SARS-CoV-2 (COVID-19) associated with upper and lower limb paralysis related to GBS [18,19,20].

The patient was then intubated for IMV due to ARDS and received five cycles of TPE with 5% albumin replacement on alternate days owing to his progressive severity status. Although TPE was performed after 3 weeks of the established disease, the patient had a significant recovery in respiratory status and muscle weakness. Previous studies have stated that TPE might be more effective if administered within 7–14 days of the onset of GBS symptoms [21,22,23]. In this case report, we did not use TPE as the main treatment at the time of admission because we tried to treat the patient in a conventional manner. However, TPE was performed when the patient’s respiratory symptoms worsened, manifested by ARDS requiring intubation for IMV; and corticosteroids were used for the treatment of ARDS as recommended by standard guidelines. Similar to our previous case report concerning GBS due to severe COVID-19, the current patient had total recovery 6 months after disease onset (Fig. 2).

Fig. 2
figure 2

Symptoms, diagnosis, and treatment of a reported patient. GBS Guillain–Barré syndrome, TPE therapy plasma exchange

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Previous studies have demonstrated that TPE can improve the outcomes of patients with COVID-19 with a high risk of thrombosis or ARDS [24,25,26,27,28]. In this case report, the patient’s respiratory and neurological symptoms improved after five cycles of TPE. Thus, this treatment is appropriate for patients with GBS associated with ARDS in severe COVID-19. This suggests that TPE could be effective for the treatment of GBS due to administration of vaccination 2 weeks after disease onset in combination with conventional therapy. Although GBS related to vaccination is not a rare complication, this case report might be the first to reveal GBS due to Vero Cell after more than a million doses of this kind of vaccine were administered to the Vietnamese population during the outbreak of the COVID-19 pandemic.

However, in this case report, the main limitation is that the causal relationship between both SARS-CoV-2 vaccination or COVID-19 infection and GBS has not been clearly proven. The diagnosis of GBS due to COVID-19 vaccination (Vero Cell) was based mainly on the chronological evolution of symptoms and the diagnosis of exclusion.

Conclusions

GBS is a neurological disorder that can occur after immunization with the COVID-19 vaccine. Similar to other vaccines, Vero Cell can induce GBS in people receiving vaccine immunization. Therapeutic plasma exchange used in combination with standard treatment for patients with severe COVID-19 associated with GBS might provide a good prognosis. In the future, systematic reviews should be performed to evaluate the prevalence of GBS due to different vaccines for advising the healthcare system.