Background

Vaccines are the most promising way of combating the Coronavirus disease 2019 (COVID-19) pandemic [1]. Sinopharm vaccine, also known as the BBIBP-CorV vaccine, is one of the several candidates for COVID-19 vaccination [2]. The rapid creation of vaccines has increased the potential vaccine safety hazards. Aside from the vaccines’ mild and common side effects, some rare, serious adverse reactions, such as anaphylaxis, thrombotic thrombocytopenia, myopericarditis, and Guillain-Barré syndrome (GBS), are increasingly reported [1]. Acute transverse myelitis, acute disseminated encephalomyelitis, and acute demyelinating polyneuropathy are other unexpected neurological adverse events [3].

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare, treatable immune-mediated neuropathy, typically manifesting as a symmetric progressive or relapsing sensorimotor polyneuropathy affecting all extremities. CIDP has a challenging diagnosis and treatment since the clinical presentation is diverse and accurate biomarkers are lacking [4]. The process of axonal loss in CIDP worsens with time and adversely affects treatment response. This makes underdiagnoses and diagnostic delays highly undesirable and can cause significant impairment of quality of life [5].

Recent studies have raised the possibility of a connection between COVID-19 vaccination and CIDP. Here, we report a case of CIDP presenting with progressive symptoms of demyelinating neuropathy following the third dose of the Sinopharm vaccine. We believe that our report will contribute to the body of evidence regarding post-vaccination complications, and increase awareness among clinicians to make more informed decisions regarding patients at risk for these adverse events [6,7,8]. This case is reported in adherence to CARE guidelines.

Case presentation

A 67-year-old male presented with a progressive tingling sensation and paresthesia in both lower extremities. Seven days before the onset of symptoms, the patient received a third dose of the Sinopharm vaccine against SARS-CoV-2. He is a known case of knee arthrosis and diabetes mellitus, and his blood sugar was controlled with metformin. He was a former boxing teacher, physically fit, and weighted 85 kg. He also denied any history of recent infection.

At first, the paresthesia was neglected since the patient assumed it was a possible complication of diabetes. However, the ascending progression, followed by increasing weakness of the lower extremities to the extent that he had trouble initiating ambulation, compelled the patient to visit an orthopedic specialist. A lumbosacral magnetic resonance imaging (MRI) was requested, which revealed mild bulging of the L5-S1 intervertebral disc. Initial treatment with gabapentin 300mg twice a day (for paresthesia) and physical therapy was started. However, it did not yield any improvement, and within two months, the paresthesia and weakness extended to the upper extremities. Subsequently, five months following the initiation of symptoms, he was referred to our center for further evaluation.

On neurological examination, all cranial nerves were intact. Strength testing revealed normal strength of cervical muscles (on the Medical Research Council (MRC) scale; grade 5/5) but reduced force in all four extremities, especially in the deltoid muscle (grade 4/5) and lower extremities (proximal grade 3/5, distal grade 2/5). Additionally, wrist and finger extension-flexion power were diminished (grade 4/5), as were ankle dorsiflexion and plantar flexion (grade 2/5). Sensory testing showed an impaired sense of position and vibration and reduced pin-prick sensation in both the upper and distal lower extremities. On examination, the patient had action and postural tremor in his upper extremities, along with gait ataxia and generalized areflexia. The patient showed no sign of autonomic dysfunction, dysphagia, or incontinence.

He underwent electromyography and nerve conduction studies (EMG-NCV) and sensory nerve action potential (SNAP) in all four limbs, which revealed absent compound muscle action potentials (CMAP) amplitudes in lower limbs (tibial and peroneal nerves). Median, ulnar, and radial nerve conduction studies revealed increased distal latency and significant amplitude reduction, with significantly slowed conduction velocity and conduction block. It is worth noting that, due to the demyelination features of NCSs, conduction delay was highly remarkable (Table 1). Electromyography study revealed abnormal spontaneous activity with chronic reinnervation changes, which was more significant in the lower extremities (Table 2). These findings were in favor of chronic inflammatory demyelinating polyneuropathy (CIDP) with secondary axonal degeneration.

Due to the clinical course of the disease and considering the results of EMG-NCV, the patient underwent cerebrospinal fluid (CSF) analysis. As demonstrated in Table 3, results of CSF analysis showed elevated protein levels (protein: 210 mg/dL, normal < 45 mg/dL) without pleocytosis (WBC count: 4). Cervical MRI, vasculitis and paraneoplastic panel, and serum and urine protein electrophoresis were unremarkable.

Laboratory data including blood cell counts, basic metabolic panel, renal function test, liver function tests, thyroid function tests, vitamin B12, folate, copper, calcium, vitamin D3, hemoglobin A1C, total protein, albumin, erythrocyte sedimentation rate, C-reactive protein, urine analysis, serum protein electrophoresis, and urine protein electrophoresis were all within normal limits. Antinuclear antibody, serum perinuclear staining antineutrophil cytoplasmic antibody (P-ANCA), cytoplasmic-ANCA, and ganglioside antibody tests were negative. The human immunodeficiency virus, hepatitis B, and hepatitis C tests were also negative.

Table 1 Motor nerve conduction study in a 67-year-old male with preliminary diagnosis of CIDP
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Table 2 EMG Findings in a 67-year-old male with preliminary diagnosis of CIDP
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Table 3 Results of cerebrospinal fluid analysis in a 67-year-old male with paresthesia and weakness
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Based on the clinical presentation and EMG-NCV results, we ruled out other possible differential diagnoses, including diabetic neuropathy, diabetic amyotrophy, and other immune-mediated neuropathies. The patient was admitted with the impression of severe CIDP with secondary axonal degeneration and was treated with an initial dose of intravenous immunoglobulin (IVIg) 170 gr (2 gr/kg, weight: 85kg), along with continuing physiotherapy sessions. Following no significant improvement in the first month of treatment, a second round of treatment was started with prednisolone 50mg daily, IVIg 85 gr (1 gr/kg, 3 doses), and Azathioprine 50 mg daily, which was then advanced to 50 mg twice a day.

Following treatment with IVIg, prednisolone, and Azathioprine, the patient reported gradual, marked improvement and regained normal function of the upper extremities (grade 5/5) and the ability to stand up without assistance. Examination confirmed improved motor strength in the proximal muscles of both lower extremities but no significant improvement in the distal lower extremity muscles (grade 5/5 in the proximal and 2/5 in the distal muscles).

To assess the extent of recovery, a second CSF analysis was performed, which displayed a significant decrease in the protein level (60 mg/dL). Also, NCV findings at the 3-month follow-up showed no significant change except for the absence of spontaneous activity (fibrillation and positive sharp wave). He was discharged with ongoing IVIg treatment and a tapering dose of prednisolone, along with a routine neurology clinic follow-up.

Discussion and conclusions

Neuropathies after vaccination are rare and poorly understood events. About 1.5% of CIDP patients have a history of antecedent vaccination, which is distinctly unusual [9]. CIDP can be a challenging diagnosis due to the heterogeneity of presentations, ranging from distal versus proximal onset, symmetric versus asymmetric, and sensory versus motor variants. A slow disease onset may prevent rapid recognition and delay treatment [10]. In this study, we presented a rare complication of the BBIBP-CorV vaccine in a 67-year-old man who presented with symmetrical polyneuropathy of four limbs involvement. We further performed a literature review for all COVID-19 vaccine-induced CIDP patients, in which our findings are reported in Table 4.

Table 4 Literature review of characteristics of newly-diagnosed CIDP patients as a complication of COVID-19 vaccination
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Due to the vast number of vaccinated people, some of the neurological conditions will manifest within the post-vaccination period. Singh et al. reported a 66-year-old female with progressive lower extremity weakness after receiving the Moderna COVID-19 vaccine three months prior to the onset of symptoms. A close temporal link between the onset of symptoms and vaccination contributed to identifying the causality of this adverse event following immunization. It is critical to remember that, as with any other vaccination, any suggested link between COVID-19 vaccination and demyelinating neuropathies cannot be considered causal based on the limited case reports relative to the number of people immunized. However, the unfounded link between these two should not prevent further vaccination; rather, it should increase awareness regarding post-vaccination assessments [16, 23].

As demonstrated in Table 4, a total of 32 cases of CIDP following COVID-19 vaccination have been reported till July 2024, among which only three patients had received inactivated vaccine. Meanwhile, ten patients presented with peripheral neuropathy after mRNA vaccines, and seventeen developed such symptoms following adenovirus vector vaccines. A review by Hosseini and Askari reported that Pfizer, Moderna, AstraZeneca, and Johnson & Johnson vaccines were associated with neurological complications more than Sinopharm and other inactivated vaccines [32]. This association hints towards the fact that such adverse events are less likely following inactivated vaccines. It also emphasizes the importance of considering them in the differential diagnosis while choosing the most appropriate vaccine based on the patient’s comorbid disease and history.

Moreover, most of the reviewed patients presented with demyelinating symptoms after the first or second dose of vaccination and within 14–21 days after the administration. In contrast, our presented case developed such symptoms a week after the third dose of an inactivated vaccine, which highlights the rarity and importance of this report.

CIDP is often considered to be the chronic counterpart of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), the most common form of GBS. Around 16% of CIDP patients may present acutely mimicking GBS but are then followed by a chronic course lasting more than eight weeks [10]. Also, Luca et al. presented an uncommon variant of post-vaccination CIDP known as chronic inflammatory axonal polyneuropathy [33]. The challenge of determining whether a patient has CIDP is greatest in patients with diabetes [34]. In our case, the patient had a medical history of diabetes, which led to thinking of his first symptoms as signs of diabetic neuropathy (DPN). Similarly, Wang et al. described a case of CIDP in a young female, simulating DPN [35]. Given the overlap of clinical presentations between CIDP, DPN, and other demyelinating neuropathies, it is essential to distinguish CIDP from the mentioned conditions because misdiagnosis may lead to delayed therapy and a terrible prognosis.

Typical CIDP is characterized by symmetrical weakness in proximal and distal muscles that develops progressively over eight weeks or longer [36]. As appreciated in our case, and according to the cases mentioned in Table 4, 26 patients presented with progressive lower extremity paresthesia, weakness, or both. Also, almost all cases documented diminished or absent tendon reflexes and gait ataxia. Acknowledgment of these presenting signs and symptoms will further help physicians in the timely diagnosis of this condition.

Laboratory tests are crucial in eliminating other causes of peripheral neuropathy. Recent reports have shown that lab tests are usually within normal limits [37]. On CSF analysis, elevated protein concentration is a common finding similar to our case. Around 90% of patients with CIDP have a high CSF protein level without pleocytosis [10, 16]. As evidenced in many studies, spinal MRI, as the main imaging modality, can support the diagnosis of CIDP by showing contrast enhancement of the cauda equina or lumbosacral nerve roots. MRI results of our patient were unremarkable except for a mild herniated intervertebral disc. However, the patient’s spinal MRI did not have findings consistent with any other neurological condition [16, 22, 37]. EMG-NCV findings of our case were aligned with that of many other studies revealing primary demyelination of peripheral nerves, which is compatible with CIDP [20, 22, 35]. CSF analysis, electrophysiological studies, and MRI results are important diagnostics for excluding other possible causes. Of note, the absence of electrophysiological or histological evidence consistent with CIDP does not preclude the diagnosis, and it is essential to look at the diagnostic panel as a whole.

Just like our case, the management of CIDP patients is divided into pharmacological and non-pharmacological interventions. The central axis of non-pharmacological management is rehabilitation [38]. As supported by the recent literature, IVIg, prednisolone, and plasmapheresis are the recognized standard treatments for CIDP, either alone or in combination. Azathioprine, cyclophosphamide, cyclosporin A, and interferon-a are a few of the additional medications that are helpful for patients who did not respond to the above-mentioned treatment options [36, 37, 39]. Proper response to first-line treatment options is warranted by the early diagnosis of this condition.

In conclusion, CIDP should be considered a rare complication following the COVID-19 vaccination. While the benefits of immunization outweigh the risks, healthcare providers should be aware of this potential complication. Our review of the literature adds to the limited evidence, implying the role of vaccination in the pathogenesis of CIDP, and points out the importance and rarity of these conditions following inactivated vaccines. This report also provides one of the first detailed descriptions of chronic inflammatory neuropathies triggered by the Sinopharm vaccine.