A new pre-print paper at bioRxiv reveals that spike proteins from mRNA jabs are relocating to the brain tissue of vaccinated people.
Researchers found that spike proteins from the shots accumulates in the skull marrow, brain meninges, and brain parenchyma, further explaining that the “injection of the spike proteins alone caused cell death in the brain, highlighting a direct effect on brain tissue.”
threadreaderapp.com/thread/1656098725310103553.html
Link to study:
eurjmedres.biomedcentral.com/articles/10.1186/s40001-023-00992-0
A new pre-print paper at bioRxiv reveals that spike proteins from mRNA jabs are relocating to the brain tissue of vaccinated people.
Researchers found that spike proteins from the shots accumulates in the skull marrow, brain meninges, and brain parenchyma, further explaining that the “injection of the spike proteins alone caused cell death in the brain, highlighting a direct effect on brain tissue.”
Even long after a “positive” COVID test and infection has passed, spike proteins can continue to remain lodged in the human brain. Researchers say these lingering spike proteins could contribute to long-term neurological symptoms such as brain “fog” and brain tissue loss.
It turns out that numerous peer-reviewed studies even back in 2021 revealed that spike proteins from the injections lodge themselves throughout the body and stay there, deactivating a person’s telomerase, causing premature aging and possible death.
Archive of study:
A review of neurological side effects of COVID-19 vaccination
Roya Hosseini & Nayere Askari
European Journal of Medical Research volume 28, Article number: 102 (2023) Cite this article
42k Accesses
1328 Altmetric
Metricsdetails
Abstract
Following the COVID-19 virus epidemic, extensive, coordinated international research has led to the rapid development of effective vaccines. Although vaccines are now considered the best way to achieve collective safety and control mortality, due to the critical situation, these vaccines have been issued the emergency use licenses and some of their potential subsequence side effects have been overlooked. At the same time, there are many reports of side effects after getting a COVID-19 vaccine. According to these reports, vaccination can have an adverse event, especially on nervous system. The most important and common complications are cerebrovascular disorders including cerebral venous sinus thrombosis, transient ischemic attack, intracerebral hemorrhage, ischemic stroke, and demyelinating disorders including transverse myelitis, first manifestation of MS, and neuromyelitis optica. These effects are often acute and transient, but they can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting neurological side effects of COVID-19 vaccines in international databases from 2020 to 2022 and discussed neurological disorders possibly caused by vaccination.
Background
In December 2019, the SARS Covid-2 virus was introduced to the world. A virus that was much more contagious than SARS Covid-1 and spread to different parts of the world in a short time. Following that situation in 2020, the World Health Organization had to declare a global health emergency. This virus is known to cause widespread lung infection and hypoxia [1]. As of November 2022, 630.3 million people have been diagnosed with COVID-19 and 6.58 million deaths worldwide, according to WHO figures [2].
In early 2021, the first vaccines were introduced to stop the pandemic. Also, approximately 68.2% of the world's population has been fully vaccinated against this disease. There are four major strategies for producing COVID-19 vaccines, including nucleic acid-based vaccine (DNA–mRNA), viral vector (replication–non-replication), live inactivated (or attenuated) virus, and protein (spike protein or its subunits). In nucleic acid and adenovirus-based vaccines, fragments of the virus mRNA or genome enter human cells and induce the production of viral proteins [3]. These viral proteins are eventually identified as antigens and stimulate antibody production. In vaccines containing inactive or protein viruses, virus particles and proteins, as antigens, trigger the immune system [4]. As of November 2021, 11 candidate vaccines for COVID-19 have been approved by the World Health Organization for mass vaccination after leaving phase 3 of clinical studies. However, in order to prove the effectiveness of the vaccine in terms of safety and side effects, the implementation of phase 4 of clinical studies is necessary. Because the results of the phase 4 studies are the proper criteria for how the vaccine works in the real world [5].
Vaccines have always been known to be the most effective and safest drugs; however, different side effects have been identified for them, for example, the link between influenza, hepatitis, and HPV vaccines with demyelinating syndromes has been discovered, and the injection of influenza vaccine is a reason for the incidence of narcolepsy in young people [6].
Because COVID-19 vaccines are urgently approved, meaning they do not complete the standard clinical trials, the adverse effects of each vaccine should be closely monitored. It is necessary to pay attention to the fact that in mass vaccination, due to different races, disease history, age, lifestyle, and other effective factors, the incidence of adverse effects of vaccination is higher. According to data from the CDC, VAERS, and EMA databases, the short-term outcome of COVID-19 vaccination is promising, but in the medium and long term, especially with some vaccines, side effects have been reported that are worrisome. VST is the most severe disorder that should be diagnosed and controlled immediately. Therefore, physicians and personnel of medical centers related to these patients should recognize these complications and intervene as soon as possible.
Search method
Research, Review, and Case Report articles related to adverse effects of COVID-19 vaccination from 2020 to February 2022 were searched and reviewed in Google Scholar, PubMed, and NCBI databases. Many Case Report articles were not considered due to the lack of a convincing link between the complication and vaccination. Keywords used for this search included COVID-19, SARS-CoV-2, vaccination, side effects, complications, vascular thrombosis, thrombocytopenia, myelitis, demyelination, and all kind of mRNA vaccines, Adenovirus vaccine, Pfizer, AstraZeneca, Johnson & Johnson, Moderna, Sinovac, Sinopharm, Sputnik, and Covaxin. For ease of understanding the various side effects of COVID-19 vaccination, the main categories are shown in Fig. 1.
Fig. 1
figure 1
Classification of neurological complications observed after COVID-19 vaccination
Full size image
Neurological complications following COVID-19 vaccination
According to reports published in the VAERS database, COVID-19 vaccines have several local and systemic neurological complications that occur in different people, from mild to severe, depending on age, sex, history of the disease, and pre-existing immunity [7]. Complications usually appear within one day to 1 month after injection and are usually acute, transient, and self-limiting, but in severe cases lead to hospitalization and intensive care [8]. On the other hand, women have the highest incidence of neurological complications because they induce a stronger immune response against foreign antigens, which can lead to the targeting of self-antigens and lead to autoimmune disorders [9]. Adverse reactions after the second dose of the vaccine are reported more than in the first dose [5].
Mild neurological effects of the COVID-19 vaccine include weakness, numbness, headache, dizziness, imbalance, fatigue, muscle spasms, joint pain, and restless leg syndrome are more common, while tremors, tinnitus, and herpes zoster are less common. On the other hand, severe neurological complications included Bell's palsy, Guillain–Barre syndrome (GBS), stroke, seizures, anaphylaxis, and demyelinating syndromes such as transverse myelitis and acute encephalomyelitis [10]. Among these, the most dangerous neurological complication caused by COVID-19 vaccines, especially adenovirus-based, is cerebral venous sinus thrombosis in women of childbearing age [8].
According to the WHO, in the case of side effects of inactivated virus-based vaccines, especially Sinopharm, the most common local and systemic adverse reactions are injection site reactions, fatigue, fever, headache, and allergic dermatitis, which are self-limiting, and the person does not need to be hospitalized [11, 12]. It is noteworthy that rare and scattered reports have been published on the side effects of Sinopharm and other inactivated virus-based vaccines (Table 1). Vaccine reactivity has been linked to a temporary increase in inflammatory cytokines that act on blood vessels, muscles, and other tissues. In other words, we will observe the flu-like syndrome for several consecutive days after vaccination [13]. According to a recent report on the Sputnik vaccine, side effects are included headache, joint pain, fever, and flu-like symptoms [14]. According to published information on the side effects of other adenovirus vaccines, it is essential to properly evaluate the efficacy of the Sputnik vaccine and publish relevant data to decide on its side effects. COVID-19 vaccination can sometimes have severe side effects on nervous system, including the brain, spinal cord, cranial nerves, and peripheral nerves, and has been shown to have adverse vascular, metabolic, inflammatory, and functional effects on the brain [1].
Table 1 Reported neurological complications for inactivated virus-based vaccines
Full size table
The two main mechanisms, ectopic immune reactions, and molecular mimicry, have been proposed for the pathogenicity of vaccines and how these complications occur.
Headache
The first and most common systemic side effect of COVID-19 vaccines is headache, which is mild to severe and is felt in the frontal area of the head. Post-vaccination headaches can be caused by stress, vascular spasm, and intracerebral or subarachnoid hemorrhage. Vaccines based on mRNA and adenovirus have been reported to be most likely to cause headaches [26].
Vascular complications in the brain
Due to the activity of the immune system, after the injection of COVID-19 vaccines, especially adenovirus-based type, thrombocytopenia, cerebral venous sinus thrombosis, ischemic stroke and intracerebral hemorrhage, have also been reported [27]. The proposed mechanism for thrombocytopenia is the synthesis of IgG antibodies against platelet factor 4 (PF4), which activates platelets and blood clots in large venous arteries [28]. Adenovirus-based vaccines are at the forefront of causing this complication due to the transfer of the nucleic acids encoding the viral spike (S) protein. Due to the leakage of these genetic materials and their binding to factor 4 platelet, autoimmunity develops [29]. Venous sinus thrombosis is associated with excessive coagulation. Vaccine viral antigens activate platelets or indirectly cause blood to clot by activating complement pathways and increasing thrombin production. Venous sinus thrombosis and cerebral hemorrhage are more common in women between the ages of 30 and 50 than in men (Table 2) [8].
Table 2 Reported neurological complications for adenovirus-based vaccines
Full size table
Acute neurological disorders
These disorders include, transverse myelitis, acute diffuse encephalomyelitis (ADEM), Bell’s palsy, GBS, encephalopathy and seizures. Each type of vaccine can play a different role in increasing the risk of manifestation of these disorders (Tables 2, 3). The COVID-19 vaccine-related convulsions can be attributed to the synthesis and release of spike proteins, which cause severe inflammation and hyperthermia. Hyperthermia, in turn, increases glial cell activity and increases blood–brain barrier permeability. Following these events, as expected, peripheral blood cells and albumin enter the brain and disrupt the osmotic balance [10]. In connection with brain disorders, the possible mechanism is the entry of inflammatory mediators secreted by peripheral blood cells into the brain and the destruction of myelin and axonal degeneration. The presence of SARS-CoV-2 spike domain S1 antibodies in CSF may explain neurological complications after vaccination, such as encephalopathy and seizures [61].
Table 3 Reported neurological complications for mRNA-based vaccines
Full size table
Transverse myelitis is an inflammation of a part of the spinal cord that usually occurs after infection and is associated with impaired sensory, motor, and autonomic function (bladder and intestines) in areas below the area of inflammation in the spinal cord. The mechanism of induction of this disorder is the development of autoimmunity by molecular mimicry. In fact, the viral antigens of the vaccine stimulate an immunological response in the spinal cord [62]. Transverse myelitis has been observed after injection of mRNA and adenovirus-based vaccines, and it is noteworthy that mRNA-based vaccines can cause exacerbation or early manifestation of MS and neuromyelitis optica. More generally, the majority of demyelinating syndromes are related to mRNA-based vaccines, followed by adenovirus-based vaccines. According to reports, these complications are more common in men and women between the ages of 20 and 60 [9].
COVID-19 vaccination also affects the cranial and peripheral nerves and causes side effects such as Bell's palsy (facial nerve palsy—7 cranial nerve), abducens nerve palsy (lateral rectus ocular muscle nerve palsy—6 cranial nerve), impaired vision, olfactory, hearing, Guillain–Barre syndrome (GBS), small fiber neuropathy, Parsonage–Turner syndrome, and also herpes zoster. In this case, too, the known mechanism is the induction of autoimmunity by molecular mimicry. Bell's palsy and small fiber neuropathy are more commonly observed in mRNA-based vaccines [63, 64]. GBS is also a peripheral nerves and nerve roots injury that presents with severe motor weakness and paralysis of the legs or four limbs and is more common in the elderly after vaccination with adenovirus-based vaccines [65]. There have been many reports of the Pfizer vaccine being associated with olfactory [66], visual [67], auditory [68, 69], and sometimes abducens nerve palsy. Olfactory dysfunction ranges from a lack of sense of smell to an olfactory hallucination (phantosmia) that results from a bilateral disturbance or enhancement of the olfactory pathway and the olfactory bulb. Hearing disorders can vary from hearing loss to tinnitus and dizziness. Also, there is ample evidence that the Pfizer and AstraZeneca vaccines are associated with optic nerve inflammation and vision disorders and are more common in middle-aged people [70].
Herpes zoster is a disease that occurs as a result of the reactivation of the varicella-zoster virus (VZV) after receiving the COVID-19 vaccine. The process that causes the disorder is probably explained by the fact that the varicella-zoster virus CD8+ killer cells, after vaccination, are temporarily unable to control VZV due to the extensive change of simple CD8+ cells to the COVID-19 virus CD8+ killer cells. Therefore, vaccination is like a shock to the recurrence of VZV and subsequent herpes zoster [71]. mRNA-based vaccines can increase the risk of herpes zoster [72]. There was a recent report of Ramsey Hunt Syndrome (RHS after the Pfizer vaccination. RHS leads to facial nerve palsy, vestibulocochlear neuropathy, and glossopharyngeal nerve neuropathy, so it causes numbness of the face, tongue, and hearing loss. In addition, skin blisters have been observed in the ear area, leading us to hypothesize that reactivation of VZV could be a cause for RHS as well as Bell's palsy [71].
Conclusion
According to the vaccine study literature, adverse effects have always been part of the mass vaccination strategy, but ultimately the desired effects of the vaccination are more significant. Side effects of COVID-19 vaccination have been reported more frequently in people with a history of immune-related diseases or who are more sensitive to age and physiological conditions. The most important and most common complications are cerebral venous sinus thrombosis (more about AstraZeneca), transverse myelitis (more about Pfizer, Moderna, AstraZeneca, and Johnson & Johnson), Bell's palsy (more about Pfizer, Moderna, AstraZeneca), GBS (more about Pfizer, AstraZeneca, and Johnson & Johnson), and the first manifestation of MS (more about Pfizer). Finally, discovering whether these disorders are accidental or whether the vaccine is the main cause of them requires future studies, ongoing efforts to gather evidence, and long-term monitoring.
Availability of data and materials
Not applicable.
References
Garg RK, Paliwal VK. Spectrum of neurological complications following COVID-19 vaccination. Neurol Sci. 2021. https://doi.org/10.1007/s10072-021-05662-9.
Article
PubMed
PubMed Central
Google Scholar
who.int. https://covid19.who.int/mapFilter=deaths. Accessed 13 Novr 2022
Nagy A, Alhatlani B. An overview of current COVID-19 vaccine platforms. Comput Struct Biotechnol J. 2021;19:2508–17.
Article
CAS
PubMed
PubMed Central
Google Scholar
Abraham G, Bhalala OG, de Bakker PI, Ripatti S, Inouye M. Towards a molecular systems model of coronary artery disease. Curr Cardiol Rep. 2014;16(6):1–10.
Article
Google Scholar
Al Khames Aga QA, Alkhaffaf WH, Hatem TH, Nassir KF, Batineh Y, Dahham AT, Shaban D, Al Khames Aga LA, Agha MY, Traqchi M. Safety of COVID-19 vaccines. J Med Virol. 2021;93(12):6588–94.
Article
CAS
PubMed
PubMed Central
Google Scholar
Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. Autoimmun Rev. 2014;13(3):215–24.
Article
PubMed
Google Scholar
Dutta S, Kaur R, Charan J, Bhardwaj P, Ambwani SR, Babu S, Goyal JP, Haque M. Analysis of neurological adverse events reported in VigiBase from COVID-19 vaccines. Cureus. 2022. https://doi.org/10.7759/cureus.21376.
Article
PubMed
PubMed Central
Google Scholar
Finsterer J. Neurological side effects of SARS-CoV-2 vaccinations. Acta Neurol Scand. 2022;145(1):5–9.
Article
CAS
PubMed
Google Scholar
Ismail II, Salama S. A systematic review of cases of CNS demyelination following COVID-19 vaccination. J Neuroimmunol. 2022;362: 577765.
Article
CAS
PubMed
Google Scholar
Assiri SA, Althaqafi RM, Alswat K, Alghamdi AA, Alomairi NE, Nemenqani DM, Ibrahim ZS, Elkady A. Post COVID-19 vaccination-associated neurological complications. Neuropsychiatr Dis Treat. 2022;18:137.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ghiasi N, Valizadeh R, Arabsorkhi M, Hoseyni TS, Esfandiari K, Sadighpour T, Jahantigh HR. Efficacy and side effects of Sputnik V, Sinopharm and AstraZeneca vaccines to stop COVID-19; a review and discussion. Immunopathologia Persa. 2021;7(2):31.
Article
Google Scholar
Saeed BQ, Al-Shahrabi R, Alhaj SS, Alkokhardi ZM, Adrees AO. Side effects and perceptions following Sinopharm COVID-19 vaccination. Int J Infect Dis. 2021;111:219–26.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, Han W, Chen Z, Tang R, Yin W. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021;21(2):181–92.
Article
CAS
PubMed
Google Scholar
Kadyrova I, Yegorov S, Negmetzhanov B, Kolesnikova Y, Kolesnichenko S, Korshukov I, Baiken Y, Matkarimov B, Miller MS, Hortelano GH. Sputnik-V reactogenicity and immunogenicity in the blood and mucosa: a prospective cohort study. medRxiv. 2022. https://doi.org/10.1038/s41598-022-17514-3.
Article
Google Scholar
Cao L, Ren L. Acute disseminated encephalomyelitis after severe acute respiratory syndrome coronavirus 2 vaccination: a case report. Acta Neurol Belg. 2021;122(3):793–5.
Article
PubMed
PubMed Central
Google Scholar
Erdem NŞ, Demirci S, Özel T, Mamadova K, Karaali K, Çelik HT, Uslu FI, Özkaynak SS. Acute transverse myelitis after inactivated COVID-19 vaccine. Ideggyogyaszati Szemle. 2021;74(7–08):273–6.
Article
PubMed
Google Scholar
Khan E, Shrestha AK, Colantonio MA, Liberio RN, Sriwastava S. Acute transverse myelitis following SARS-CoV-2 vaccination: a case report and review of literature. J Neurol. 2021;269(3):1121–32.
Article
PubMed
PubMed Central
Google Scholar
Malhotra HS, Gupta P, Prabhu V, Garg RK, Dandu H, Agarwal V. COVID-19 vaccination-associated myelitis. QJM: An Int J Med. 2021. https://doi.org/10.1093/qjmed/hcab069.
Article
Google Scholar
Corrêa DG, Cañete LAQ, Dos Santos GAC, de Oliveira RV, Brandão CO, da Cruz Jr LCH. Neurological symptoms and neuroimaging alterations related with COVID-19 vaccine: Cause or coincidence? Clin Imaging. 2021;80:348–52.
Article
PubMed
PubMed Central
Google Scholar
Ozgen Kenangil G, Ari BC, Guler C, Demir MK. Acute disseminated encephalomyelitis-like presentation after an inactivated coronavirus vaccine. Acta Neurol Belg. 2021;121(4):1089–91.
Article
PubMed
PubMed Central
Google Scholar
Chen S, Fan X-R, He S, Zhang J-W, Li S-J. Watch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19. Neurol Sci. 2021;42(9):3537–9.
Article
PubMed
PubMed Central
Google Scholar
Seyed Ahadi M, Ghadiri F, Naser Moghadasi A. Acute attack in a patient with multiple sclerosis 2 days after COVID vaccination: a case report. Acta Neurol Belg. 2021. https://doi.org/10.1007/s13760-021-01775-2.
Article
PubMed
PubMed Central
Google Scholar
Burrows A, Bartholomew T, Rudd J, Walker D. Sequential contralateral facial nerve palsies following COVID-19 vaccination first and second doses. BMJ Case Reports CP. 2021;14(7): e243829.
Article
Google Scholar
Ercoli T, Lutzoni L, Orofino G, Muroni A, Defazio G. Functional neurological disorder after COVID-19 vaccination. Neurol Sci. 2021;42(10):3989–90.
Article
PubMed
PubMed Central
Google Scholar
Ish S, Ish P. Facial nerve palsy after COVID-19 vaccination–A rare association or a coincidence. Indian J Ophthalmol. 2021;69(9):2550.
Article
PubMed
PubMed Central
Google Scholar
Ekizoglu E, Gezegen H, Yalınay Dikmen P, Orhan EK, Ertaş M, Baykan B (2021) The characteristics of COVID-19 vaccine-related headache: Clues gathered from the healthcare personnel in the pandemic. Cephalalgia. 42(4–5):366–75.
PubMed
PubMed Central
Google Scholar
Schulz JB, Berlit P, Diener HC, Gerloff C, Greinacher A, Klein C, Petzold GC, Piccininni M, Poli S, Röhrig R. COVID-19 vaccine-associated cerebral venous thrombosis in Germany. Ann Neurol. 2021;90(4):627–39.
Article
CAS
PubMed
PubMed Central
Google Scholar
Iba T, Levy JH, Warkentin TE. Recognizing vaccine-induced immune thrombotic thrombocytopenia. Crit Care Med. 2022;50(1): e80.
Article
CAS
PubMed
Google Scholar
McGonagle D, De Marco G, Bridgewood C. Mechanisms of immunothrombosis in vaccine-induced thrombotic thrombocytopenia (VITT) compared to natural SARS-CoV-2 infection. J Autoimmun. 2021;121: 102662.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bourguignon A, Arnold DM, Warkentin TE, Smith JW, Pannu T, Shrum JM, Al Maqrashi ZA, Shroff A, Lessard M-C, Blais N. Adjunct immune globulin for vaccine-induced immune thrombotic thrombocytopenia. New Engl J Med. 2021;385(8):720–8.
Article
CAS
PubMed
Google Scholar
Clark RT, Johnson L, Billotti J, Foulds G, Ketels T, Heard K, Hynes EC. Early outcomes of bivalirudin therapy for thrombotic thrombocytopenia and cerebral venous sinus thrombosis after Ad26. COV2.S vaccination. Ann Emergency Med. 2021;78(4):511–4.
Article
Google Scholar
D’agostino V, Caranci F, Negro A, Piscitelli V, Tuccillo B, Fasano F, Sirabella G, Marano I, Granata V, Grassi R. A rare case of cerebral venous thrombosis and disseminated intravascular coagulation temporally associated to the COVID-19 vaccine administration. J Personal Med. 2021;11(4):285.
Article
Google Scholar
Franchini M, Testa S, Pezzo M, Glingani C, Caruso B, Terenziani I, Pognani C, Bellometti SA, Castelli G. Cerebral venous thrombosis and thrombocytopenia post-COVID-19 vaccination. Thromb Res. 2021;202:182–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
García-Azorín D, Do TP, Gantenbein AR, Hansen JM, Souza MNP, Obermann M, Pohl H, Schankin CJ, Schytz HW, Sinclair A. Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis. J Headache Pain. 2021;22(1):1–5.
Article
Google Scholar
George G, Friedman KD, Curtis BR, Lind SE. Successful treatment of thrombotic thrombocytopenia with cerebral sinus venous thrombosis following Ad26. COV2. S vaccination. Am J Hematol. 2021;96(8):E301–3.
Article
CAS
PubMed
Google Scholar
Ramdeny S, Lang A, Al-Izzi S, Hung A, Anwar I, Kumar P. Management of a patient with a rare congenital limb malformation syndrome after SARS-CoV-2 vaccine-induced thrombosis and thrombocytopenia (VITT). Br J Haematol. 2021. https://doi.org/10.1111/bjh.17619.
Article
PubMed
PubMed Central
Google Scholar
Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, Goldblatt D, Kotoucek P, Thomas W, Lester W. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. New Engl J Med. 2021;384(23):2202–11.
Article
CAS
PubMed
Google Scholar
Sharifian-Dorche M, Bahmanyar M, Sharifian-Dorche A, Mohammadi P, Nomovi M, Mowla A. Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review. J Neurol Sci. 2021;428: 117607.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gao J-J, Tseng H-P, Lin C-L, Shiu J-S, Lee M-H, Liu C-H. Acute transverse myelitis following COVID-19 vaccination. Vaccines. 2021;9(9):1008.
Article
CAS
PubMed
PubMed Central
Google Scholar
Notghi AA, Atley J, Silva M. Lessons of the month 1: Longitudinal extensive transverse myelitis following AstraZeneca COVID-19 vaccination. Clin Med (Northfield Il). 2021;21(5): e535.
Article
Google Scholar
Pagenkopf C, Südmeyer M. A case of longitudinally extensive transverse myelitis following vaccination against Covid-19. J Neuroimmunol. 2021;358: 577606.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tahir N, Koorapati G, Prasad S, Jeelani HM, Sherchan R, Shrestha J, Shayuk M. SARS-CoV-2 vaccination-induced transverse myelitis. Cureus. 2021. https://doi.org/10.7759/cureus.16624.
Article
PubMed
PubMed Central
Google Scholar
Vegezzi E, Ravaglia S, Buongarzone G, Bini P, Diamanti L, Gastaldi M, Prunetti P, Rognone E, Marchioni E. Acute myelitis and ChAdOx1 nCoV-19 vaccine: casual or causal association? J Neuroimmunol. 2021;359: 577686.
Article
CAS
PubMed
PubMed Central
Google Scholar
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet. 2021;397(10269):99–111.
Article
CAS
Google Scholar
Allen CM, Ramsamy S, Tarr AW, Tighe PJ, Irving WL, Tanasescu R, Evans JR. Guillain-Barré syndrome variant occurring after SARS-CoV-2 vaccination. Ann Neurol. 2021;90(2):315–8.
Article
CAS
PubMed
Google Scholar
Bonifacio GB, Patel D, Cook S, Purcaru E, Couzins M, Domjan J, Ryan S, Alareed A, Tuohy O, Slaght S. Bilateral facial weakness with paraesthesia variant of Guillain-Barré syndrome following Vaxzevria COVID-19 vaccine. J Neurol Neurosurg Psychiatry. 2021. https://doi.org/10.1136/jnnp-2021-327027.
Article
PubMed
Google Scholar
Hasan T, Khan M, Khan F, Hamza G. Case of Guillain-Barré syndrome following COVID-19 vaccine. BMJ Case Reports CP. 2021;14(6): e243629.
Article
Google Scholar
Kohli S, Varshney M, Mangla S, Jaiswal B, Chhabra PH. Guillain-Barré syndrome after COVID-19 vaccine: should we assume a causal Link? Int J Med Pharm Case Rep: 20-24. 2021. https://doi.org/10.9734/ijmpcr/2021/v14i130124.
Article
Google Scholar
Permezel F, Borojevic B, Lau S, de Boer HH. Acute disseminated encephalomyelitis (ADEM) following recent Oxford/AstraZeneca COVID-19 vaccination. Forensic Sci Med Pathol. 2021. https://doi.org/10.1007/s12024-021-00440-7.
Article
PubMed
PubMed Central
Google Scholar
Bjørnstad-Tuveng TH, Rudjord A, Anker P. Fatal cerebral haemorrhage after COVID-19 vaccine. Tidsskrift for Den norske legeforening. 2021. https://doi.org/10.4045/tidsskr.21.0312.
Article
PubMed
Google Scholar
Baldelli L, Amore G, Montini A, Panzera I, Rossi S, Cortelli P, Guarino M, Rinaldi R, D’Angelo R. Hyperacute reversible encephalopathy related to cytokine storm following COVID-19 vaccine. J Neuroimmunol. 2021;358: 577661.
Article
CAS
PubMed
PubMed Central
Google Scholar
Antonio Crespo Burillo J, Martínez CL, Arguedas CG, Pueyo FJM. Amyotrophic neuralgia secondary to Vaxzevria (AstraZeneca) COVID-19 vaccine. Neurologia (Barc, Ed impr). 2021. https://doi.org/10.1016/j.nrleng.2021.05.002.
Article
Google Scholar
Alpalhão M, Filipe P. Herpes Zoster following SARS-CoV-2 vaccination–a series of four cases. J Eur Acad Dermatol Venereol. 2021. https://doi.org/10.1111/jdv.17555.
Article
PubMed
PubMed Central
Google Scholar
Tseng P-T, Chen T-Y, Sun Y-S, Chen Y-W, Chen J-J. The reversible tinnitus and cochleopathy followed first-dose AstraZeneca COVID-19 vaccination. QJM An Int J Med. 2021. https://doi.org/10.1093/qjmed/hcab210.
Article
Google Scholar
Finsterer J, Scorza FA, Scorza CA. Post SARS-CoV-2 vaccination Guillain-Barre syndrome in 19 patients. Clinics. 2021. https://doi.org/10.6061/clinics/2021/e3286.
Article
PubMed
PubMed Central
Google Scholar
Introna A, Caputo F, Santoro C, Guerra T, Ucci M, Mezzapesa DM, Trojano M. Guillain-Barré syndrome after AstraZeneca COVID-19-vaccination: a causal or casual association? Clin Neurol Neurosurg. 2021;208: 106887.
Article
PubMed
PubMed Central
Google Scholar
Jain E, Pandav K, Regmi P, Michel G, Altshuler I. Facial diplegia: a rare, atypical variant of Guillain-Barré syndrome and Ad26. COV2. S Vaccine. Cureus. 2021. https://doi.org/10.7759/cureus.16612.
Article
PubMed
PubMed Central
Google Scholar
Loza AMM, Holroyd KB, Johnson SA, Pilgrim DM, Amato AA. Guillain-Barré syndrome in the placebo and active arms of a COVID-19 vaccine clinical trial: temporal associations do not imply causality. Neurology. 2021;96(22):1052–4.
Article
Google Scholar
Malik B, Kalantary A, Rikabi K, Kunadi A. Pulmonary embolism, transient ischaemic attack and thrombocytopenia after the Johnson & Johnson COVID-19 vaccine. BMJ Case Reports CP. 2021;14(7): e243975.
Article
Google Scholar
Etemadifar M, Sigari AA, Sedaghat N, Salari M, Nouri H. Acute relapse and poor immunization following COVID-19 vaccination in a rituximab-treated multiple sclerosis patient. Hum Vaccin Immunother. 2021;17(10):3481–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fan H-T, Lin Y-Y, Chiang W-F, Lin C-Y, Chen M-H, Wu K-A, Chan J-S, Kao Y-H, Shyu H-Y, Hsiao P-J. COVID-19 vaccine-induced encephalitis and status epilepticus. QJM: An Int J Med. 2022. https://doi.org/10.1093/qjmed/hcab335.
Article
Google Scholar
Román GC, Gracia F, Torres A, Palacios A, Gracia K, Harris D. Acute transverse myelitis (ATM): clinical review of 43 patients with COVID-19-associated ATM and 3 post-vaccination ATM serious adverse events with the ChAdOx1 nCoV-19 vaccine (AZD1222). Front Immunol. 2021;12:879.
Article
Google Scholar
Ozonoff A, Nanishi E, Levy O. Bell’s palsy and SARS-CoV-2 vaccines. Lancet Infect Dis. 2021;21(4):450–2.
Article
CAS
PubMed
PubMed Central
Google Scholar
Waheed W, Carey ME, Tandan SR, Tandan R. Post COVID-19 vaccine small fiber neuropathy. Muscle Nerve. 2021;64(1):E1.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dyer O. Covid-19: Regulators warn that rare Guillain-Barré cases may link to J&J and AstraZeneca vaccines. Br Med J Publ Gr. 2021. https://doi.org/10.1136/bmj.n1786.
Article
Google Scholar
Keir G, Maria NI, Kirsch CF. Unique imaging findings of neurologic phantosmia following Pfizer-BioNtech COVID-19 vaccination: a case report. Top Magn Reson Imaging. 2021;30(3):133–7.
Article
PubMed
Google Scholar
Santovito LS, Pinna G. Acute reduction of visual acuity and visual field after Pfizer-BioNTech COVID-19 vaccine 2nd dose: a case report. Inflammation Res. 2021;70(9):931–3.
Article
CAS
Google Scholar
Parrino D, Frosolini A, Gallo C, De Siati RD, Spinato G, de Filippis C. Tinnitus following COVID-19 vaccination: report of three cases. Int J Audiol. 2021. https://doi.org/10.1080/14992027.2021.1931969.
Article
PubMed
Google Scholar
Wichova H, Miller ME, Derebery MJ. Otologic manifestations after COVID-19 vaccination: the house ear clinic experience. Otol Neurotol. 2021;42(9): e1213.
Article
PubMed
PubMed Central
Google Scholar
Žorić L, Rajović-Mrkić I, Čolak E, Mirić D, Kisić B. Optic neuritis in a patient with seropositive myelin oligodendrocyte glycoprotein antibody during the post-COVID-19 period. Int Med Case Rep J. 2021;14:349.
Article
PubMed
PubMed Central
Google Scholar
Woo CJ, Chou OHI, Cheung BMY. Ramsay Hunt syndrome following COVID-19 vaccination. Postgrad Med J. 2022. https://doi.org/10.1136/postgradmedj-2021-141022.
Article
PubMed
Google Scholar
McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa D, Tyagi A, Desai SR, French LE, Lim HW, Thiers BH. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases. J Am Acad Dermatol. 2021;85(1):46–55.
Article
CAS
PubMed
PubMed Central
Google Scholar
Göbel CH, Heinze A, Karstedt S, Morscheck M, Tashiro L, Cirkel A, Hamid Q, Halwani R, Temsah M-H, Ziemann M. Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: a multicentre observational cohort study. Brain Commun. 2021;3(3):169.
Article
Google Scholar
Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, Voysey M, Aley PK, Angus B, Babbage G. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. The Lancet. 2020;396(10267):1979–93.
Article
CAS
Google Scholar
Havla J, Schultz Y, Zimmermann H, Hohlfeld R, Danek A, Kümpfel T. First manifestation of multiple sclerosis after immunization with the Pfizer-BioNTech COVID-19 vaccine. J Neurol. 2022;269(1):55–8.
Article
CAS
PubMed
Google Scholar
Khayat-Khoei M, Bhattacharyya S, Katz J, Harrison D, Tauhid S, Bruso P, Houtchens MK, Edwards KR, Bakshi R. COVID-19 mRNA vaccination leading to CNS inflammation: a case series. J Neurol. 2021. https://doi.org/10.1007/s00415-021-10780-7.
Article
PubMed
PubMed Central
Google Scholar
Watad A, De Marco G, Mahajna H, Druyan A, Eltity M, Hijazi N, Haddad A, Elias M, Zisman D, Naffaa ME. Immune-mediated disease flares or new-onset disease in 27 subjects following mRNA/DNA SARS-CoV-2 vaccination. Vaccines. 2021;9(5):435.
Article
CAS
PubMed
PubMed Central
Google Scholar
Alshararni A. Acute transverse myelitis associated with COVID-19 vaccine: a case report. Int J Res Pharma Sci. 2021;12:2083–7.
Article
CAS
Google Scholar
McLean P, Trefts L. Transverse myelitis 48 hours after the administration of an mRNA COVID 19 vaccine. Neuroimmunology Reports. 2021;1: 100019.
Article
CAS
PubMed Central
Google Scholar
Finsterer J. Exacerbating Guillain-Barré Syndrome Eight Days after vector-based COVID-19 vaccination. Case Rep Infect Dis. 2021. https://doi.org/10.1155/2021/3619131.
Article
PubMed
PubMed Central
Google Scholar
Ogbebor O, Seth H, Min Z, Bhanot N. Guillain-Barré syndrome following the first dose of SARS-CoV-2 vaccine: a temporal occurrence, not a causal association. IDCases. 2021;24: e01143.
Article
CAS
PubMed
PubMed Central
Google Scholar
Razok A, Shams A, Almeer A, Zahid M. Post-COVID-19 vaccine Guillain-Barré syndrome; first reported case from Qatar. Ann Med Surg. 2021;67: 102540.
Article
Google Scholar
Waheed S, Bayas A, Hindi F, Rizvi Z, Espinosa PS. Neurological complications of COVID-19: Guillain-Barre syndrome following Pfizer COVID-19 vaccine. Cureus. 2021. https://doi.org/10.7759/cureus.13426.
Article
PubMed
PubMed Central
Google Scholar
de Terreros Caro GG, Díaz SG, Alé MP, Gimeno MM. Bell’s palsy following COVID-19 vaccination: a case report. Neurologia (Barcelona, Spain). 2021. https://doi.org/10.1016/j.nrleng.2021.04.002.
Article
Google Scholar
Obermann M, Krasniqi M, Ewers N, Fayad J, Haeberle U. Bell’s palsy following COVID-19 vaccination with high CSF antibody response. Neurol Sci. 2021;42(11):4397–9.
Article
PubMed
PubMed Central
Google Scholar
Repajic M, Lai XL, Xu P, Liu A. Bell’s Palsy after second dose of Pfizer COVID-19 vaccination in a patient with history of recurrent Bell’s palsy. Brain Behav Immun Health. 2021;13: 100217.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vogrig A, Janes F, Gigli GL, Curcio F, Del Negro I, D’Agostini S, Fabris M, Valente M. Acute disseminated encephalomyelitis after SARS-CoV-2 vaccination. Clin Neurol Neurosurg. 2021;208: 106839.
Article
PubMed
PubMed Central
Google Scholar
Konstantinidis I, Tsakiropoulou E, Hähner A, de With K, Poulas K, Hummel T. Olfactory dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Int Forum Allergy Rhinol. 2021. https://doi.org/10.1002/alr.22809.
Article
PubMed
PubMed Central
Google Scholar
Ahmed SH, Waseem S, Shaikh TG, Qadir NA, Siddiqui SA, Ullah I, Waris A, Yousaf Z. SARS-CoV-2 vaccine-associated-tinnitus: a review. Ann Med Surg. 2022;75:103293.
Article
Google Scholar
Reyes-Capo DP, Stevens SM, Cavuoto KM. Acute abducens nerve palsy following COVID-19 vaccination. J Am Assoc Pediatr Ophthalmol Strabismus. 2021;25(5):302–3.
Article
Google Scholar
Chiu H-H, Wei K-C, Chen A, Wang W-H. Herpes zoster following COVID-19 vaccine: a report of three cases. QJM: An Int J Med. 2021;114(7):531–2.
Article
CAS
Google Scholar
Rodríguez-Jiménez P, Chicharro P, Cabrera L-M, Seguí M, Morales-Caballero Á, Llamas-Velasco M, Sánchez-Pérez J. Varicella-zoster virus reactivation after SARS-CoV-2 BNT162b2 mRNA vaccination: report of 5 cases. JAAD Case Rep. 2021;12:58–9.
Article
PubMed
PubMed Central
Google Scholar
Salinas MR, Dieppa M. Transient akathisia after the SARS-Cov-2 vaccine. Clin Park Relat Disord. 2021;4: 100098.
PubMed
PubMed Central
Google Scholar
Finsterer J, Redzic Z. Symptomatic peduncular, cavernous bleeding following SARS-CoV-2 vaccination induced immune thrombocytopenia. Brain Hemorrhages. 2021;2(4):169–71.
Article
CAS
PubMed
PubMed Central
Google Scholar
Blauenfeldt RA, Kristensen SR, Ernstsen SL, Kristensen CCH, Simonsen CZ, Hvas AM. Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vector-based COVID-19 vaccine. J Thromb Haemost. 2021;19(7):1771–5.
Article
CAS
PubMed
Google Scholar
Fitzsimmons W, Nance CS. Sudden onset of myelitis after COVID-19 vaccination: an under-recognized severe rare adverse event. SSRN. 2021. https://doi.org/10.2139/ssrn.3841558.
Article
Google Scholar
Martin-Villares C, Vazquez-Feito A, Gonzalez-Gimeno M, de la Nogal-Fernandez B. Bell’s palsy following a single dose of mRNA SARS-CoV-2 vaccine: a case report. J Neurol. 2022;269(1):47–8.
Article
CAS
PubMed
Google Scholar
Al-Mashdali AF, Ata YM, Sadik N. Post-COVID-19 vaccine acute hyperactive encephalopathy with dramatic response to methylprednisolone: a case report. Ann Med Surg. 2021;69: 102803.
Article
Google Scholar
Channa L, Torre K, Rothe M. Herpes zoster reactivation after mRNA-1273 (Moderna) SARS-CoV-2 vaccination. JAAD Case Rep. 2021;15:60–1.
Article
PubMed
PubMed Central
Google Scholar
Liu BD, Ugolini C, Jha P. Two cases of post-Moderna COVID-19 vaccine encephalopathy associated with nonconvulsive status epilepticus. Cureus. 2021. https://doi.org/10.7759/cureus.16172.
Article
PubMed
PubMed Central
Google Scholar
Šín R, Štruncová D. Status epilepticus as a complication after COVID-19 mRNA-1273 vaccine: a case report. World J Clin Cases. 2021;9(24):7218.
Article
PubMed
PubMed Central
Google Scholar
Athyros VG, Doumas M. A possible case of hypertensive crisis with intracranial haemorrhage after an mRNA anti-COVID-19 vaccine. Angiology. 2022;73(1):87–87.
Article
CAS
PubMed
Google Scholar
Download references
Acknowledgements
Not applicable.
Funding
Not applicable.
Author information
Authors and Affiliations
Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, P.O.Box 76135-133, Kerman, Islamic Republic of Iran
Roya Hosseini & Nayere Askari
Immunoregulation Research Center, Shahed University, Tehran, Islamic Republic of Iran
Nayere Askari
Contributions
RH: carried out the searched publications, classified the documents, and wrote the manuscript draft. NA: supervised the study and reviewed the manuscript. All authors read and approved the final manuscript.
Corresponding author
Correspondence to Nayere Askari.
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Reprints and Permissions
About this article
Verify currency and authenticity via CrossMark
Cite this article
Hosseini, R., Askari, N. A review of neurological side effects of COVID-19 vaccination. Eur J Med Res 28, 102 (2023). https://doi.org/10.1186/s40001-023-00992-0
Download citation
Received
18 June 2022
Accepted
04 January 2023
Published
25 February 2023
DOI
Roya Hosseini & Nayere Askari
European Journal of Medical Research volume 28, Article number: 102 (2023) Cite this article
42k Accesses
1328 Altmetric
Metricsdetails
Abstract
Following the COVID-19 virus epidemic, extensive, coordinated international research has led to the rapid development of effective vaccines. Although vaccines are now considered the best way to achieve collective safety and control mortality, due to the critical situation, these vaccines have been issued the emergency use licenses and some of their potential subsequence side effects have been overlooked. At the same time, there are many reports of side effects after getting a COVID-19 vaccine. According to these reports, vaccination can have an adverse event, especially on nervous system. The most important and common complications are cerebrovascular disorders including cerebral venous sinus thrombosis, transient ischemic attack, intracerebral hemorrhage, ischemic stroke, and demyelinating disorders including transverse myelitis, first manifestation of MS, and neuromyelitis optica. These effects are often acute and transient, but they can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting neurological side effects of COVID-19 vaccines in international databases from 2020 to 2022 and discussed neurological disorders possibly caused by vaccination.
Background
In December 2019, the SARS Covid-2 virus was introduced to the world. A virus that was much more contagious than SARS Covid-1 and spread to different parts of the world in a short time. Following that situation in 2020, the World Health Organization had to declare a global health emergency. This virus is known to cause widespread lung infection and hypoxia [1]. As of November 2022, 630.3 million people have been diagnosed with COVID-19 and 6.58 million deaths worldwide, according to WHO figures [2].
In early 2021, the first vaccines were introduced to stop the pandemic. Also, approximately 68.2% of the world's population has been fully vaccinated against this disease. There are four major strategies for producing COVID-19 vaccines, including nucleic acid-based vaccine (DNA–mRNA), viral vector (replication–non-replication), live inactivated (or attenuated) virus, and protein (spike protein or its subunits). In nucleic acid and adenovirus-based vaccines, fragments of the virus mRNA or genome enter human cells and induce the production of viral proteins [3]. These viral proteins are eventually identified as antigens and stimulate antibody production. In vaccines containing inactive or protein viruses, virus particles and proteins, as antigens, trigger the immune system [4]. As of November 2021, 11 candidate vaccines for COVID-19 have been approved by the World Health Organization for mass vaccination after leaving phase 3 of clinical studies. However, in order to prove the effectiveness of the vaccine in terms of safety and side effects, the implementation of phase 4 of clinical studies is necessary. Because the results of the phase 4 studies are the proper criteria for how the vaccine works in the real world [5].
Vaccines have always been known to be the most effective and safest drugs; however, different side effects have been identified for them, for example, the link between influenza, hepatitis, and HPV vaccines with demyelinating syndromes has been discovered, and the injection of influenza vaccine is a reason for the incidence of narcolepsy in young people [6].
Because COVID-19 vaccines are urgently approved, meaning they do not complete the standard clinical trials, the adverse effects of each vaccine should be closely monitored. It is necessary to pay attention to the fact that in mass vaccination, due to different races, disease history, age, lifestyle, and other effective factors, the incidence of adverse effects of vaccination is higher. According to data from the CDC, VAERS, and EMA databases, the short-term outcome of COVID-19 vaccination is promising, but in the medium and long term, especially with some vaccines, side effects have been reported that are worrisome. VST is the most severe disorder that should be diagnosed and controlled immediately. Therefore, physicians and personnel of medical centers related to these patients should recognize these complications and intervene as soon as possible.
Search method
Research, Review, and Case Report articles related to adverse effects of COVID-19 vaccination from 2020 to February 2022 were searched and reviewed in Google Scholar, PubMed, and NCBI databases. Many Case Report articles were not considered due to the lack of a convincing link between the complication and vaccination. Keywords used for this search included COVID-19, SARS-CoV-2, vaccination, side effects, complications, vascular thrombosis, thrombocytopenia, myelitis, demyelination, and all kind of mRNA vaccines, Adenovirus vaccine, Pfizer, AstraZeneca, Johnson & Johnson, Moderna, Sinovac, Sinopharm, Sputnik, and Covaxin. For ease of understanding the various side effects of COVID-19 vaccination, the main categories are shown in Fig. 1.
Fig. 1
figure 1
Classification of neurological complications observed after COVID-19 vaccination
Full size image
Neurological complications following COVID-19 vaccination
According to reports published in the VAERS database, COVID-19 vaccines have several local and systemic neurological complications that occur in different people, from mild to severe, depending on age, sex, history of the disease, and pre-existing immunity [7]. Complications usually appear within one day to 1 month after injection and are usually acute, transient, and self-limiting, but in severe cases lead to hospitalization and intensive care [8]. On the other hand, women have the highest incidence of neurological complications because they induce a stronger immune response against foreign antigens, which can lead to the targeting of self-antigens and lead to autoimmune disorders [9]. Adverse reactions after the second dose of the vaccine are reported more than in the first dose [5].
Mild neurological effects of the COVID-19 vaccine include weakness, numbness, headache, dizziness, imbalance, fatigue, muscle spasms, joint pain, and restless leg syndrome are more common, while tremors, tinnitus, and herpes zoster are less common. On the other hand, severe neurological complications included Bell's palsy, Guillain–Barre syndrome (GBS), stroke, seizures, anaphylaxis, and demyelinating syndromes such as transverse myelitis and acute encephalomyelitis [10]. Among these, the most dangerous neurological complication caused by COVID-19 vaccines, especially adenovirus-based, is cerebral venous sinus thrombosis in women of childbearing age [8].
According to the WHO, in the case of side effects of inactivated virus-based vaccines, especially Sinopharm, the most common local and systemic adverse reactions are injection site reactions, fatigue, fever, headache, and allergic dermatitis, which are self-limiting, and the person does not need to be hospitalized [11, 12]. It is noteworthy that rare and scattered reports have been published on the side effects of Sinopharm and other inactivated virus-based vaccines (Table 1). Vaccine reactivity has been linked to a temporary increase in inflammatory cytokines that act on blood vessels, muscles, and other tissues. In other words, we will observe the flu-like syndrome for several consecutive days after vaccination [13]. According to a recent report on the Sputnik vaccine, side effects are included headache, joint pain, fever, and flu-like symptoms [14]. According to published information on the side effects of other adenovirus vaccines, it is essential to properly evaluate the efficacy of the Sputnik vaccine and publish relevant data to decide on its side effects. COVID-19 vaccination can sometimes have severe side effects on nervous system, including the brain, spinal cord, cranial nerves, and peripheral nerves, and has been shown to have adverse vascular, metabolic, inflammatory, and functional effects on the brain [1].
Table 1 Reported neurological complications for inactivated virus-based vaccines
Full size table
The two main mechanisms, ectopic immune reactions, and molecular mimicry, have been proposed for the pathogenicity of vaccines and how these complications occur.
Headache
The first and most common systemic side effect of COVID-19 vaccines is headache, which is mild to severe and is felt in the frontal area of the head. Post-vaccination headaches can be caused by stress, vascular spasm, and intracerebral or subarachnoid hemorrhage. Vaccines based on mRNA and adenovirus have been reported to be most likely to cause headaches [26].
Vascular complications in the brain
Due to the activity of the immune system, after the injection of COVID-19 vaccines, especially adenovirus-based type, thrombocytopenia, cerebral venous sinus thrombosis, ischemic stroke and intracerebral hemorrhage, have also been reported [27]. The proposed mechanism for thrombocytopenia is the synthesis of IgG antibodies against platelet factor 4 (PF4), which activates platelets and blood clots in large venous arteries [28]. Adenovirus-based vaccines are at the forefront of causing this complication due to the transfer of the nucleic acids encoding the viral spike (S) protein. Due to the leakage of these genetic materials and their binding to factor 4 platelet, autoimmunity develops [29]. Venous sinus thrombosis is associated with excessive coagulation. Vaccine viral antigens activate platelets or indirectly cause blood to clot by activating complement pathways and increasing thrombin production. Venous sinus thrombosis and cerebral hemorrhage are more common in women between the ages of 30 and 50 than in men (Table 2) [8].
Table 2 Reported neurological complications for adenovirus-based vaccines
Full size table
Acute neurological disorders
These disorders include, transverse myelitis, acute diffuse encephalomyelitis (ADEM), Bell’s palsy, GBS, encephalopathy and seizures. Each type of vaccine can play a different role in increasing the risk of manifestation of these disorders (Tables 2, 3). The COVID-19 vaccine-related convulsions can be attributed to the synthesis and release of spike proteins, which cause severe inflammation and hyperthermia. Hyperthermia, in turn, increases glial cell activity and increases blood–brain barrier permeability. Following these events, as expected, peripheral blood cells and albumin enter the brain and disrupt the osmotic balance [10]. In connection with brain disorders, the possible mechanism is the entry of inflammatory mediators secreted by peripheral blood cells into the brain and the destruction of myelin and axonal degeneration. The presence of SARS-CoV-2 spike domain S1 antibodies in CSF may explain neurological complications after vaccination, such as encephalopathy and seizures [61].
Table 3 Reported neurological complications for mRNA-based vaccines
Full size table
Transverse myelitis is an inflammation of a part of the spinal cord that usually occurs after infection and is associated with impaired sensory, motor, and autonomic function (bladder and intestines) in areas below the area of inflammation in the spinal cord. The mechanism of induction of this disorder is the development of autoimmunity by molecular mimicry. In fact, the viral antigens of the vaccine stimulate an immunological response in the spinal cord [62]. Transverse myelitis has been observed after injection of mRNA and adenovirus-based vaccines, and it is noteworthy that mRNA-based vaccines can cause exacerbation or early manifestation of MS and neuromyelitis optica. More generally, the majority of demyelinating syndromes are related to mRNA-based vaccines, followed by adenovirus-based vaccines. According to reports, these complications are more common in men and women between the ages of 20 and 60 [9].
COVID-19 vaccination also affects the cranial and peripheral nerves and causes side effects such as Bell's palsy (facial nerve palsy—7 cranial nerve), abducens nerve palsy (lateral rectus ocular muscle nerve palsy—6 cranial nerve), impaired vision, olfactory, hearing, Guillain–Barre syndrome (GBS), small fiber neuropathy, Parsonage–Turner syndrome, and also herpes zoster. In this case, too, the known mechanism is the induction of autoimmunity by molecular mimicry. Bell's palsy and small fiber neuropathy are more commonly observed in mRNA-based vaccines [63, 64]. GBS is also a peripheral nerves and nerve roots injury that presents with severe motor weakness and paralysis of the legs or four limbs and is more common in the elderly after vaccination with adenovirus-based vaccines [65]. There have been many reports of the Pfizer vaccine being associated with olfactory [66], visual [67], auditory [68, 69], and sometimes abducens nerve palsy. Olfactory dysfunction ranges from a lack of sense of smell to an olfactory hallucination (phantosmia) that results from a bilateral disturbance or enhancement of the olfactory pathway and the olfactory bulb. Hearing disorders can vary from hearing loss to tinnitus and dizziness. Also, there is ample evidence that the Pfizer and AstraZeneca vaccines are associated with optic nerve inflammation and vision disorders and are more common in middle-aged people [70].
Herpes zoster is a disease that occurs as a result of the reactivation of the varicella-zoster virus (VZV) after receiving the COVID-19 vaccine. The process that causes the disorder is probably explained by the fact that the varicella-zoster virus CD8+ killer cells, after vaccination, are temporarily unable to control VZV due to the extensive change of simple CD8+ cells to the COVID-19 virus CD8+ killer cells. Therefore, vaccination is like a shock to the recurrence of VZV and subsequent herpes zoster [71]. mRNA-based vaccines can increase the risk of herpes zoster [72]. There was a recent report of Ramsey Hunt Syndrome (RHS after the Pfizer vaccination. RHS leads to facial nerve palsy, vestibulocochlear neuropathy, and glossopharyngeal nerve neuropathy, so it causes numbness of the face, tongue, and hearing loss. In addition, skin blisters have been observed in the ear area, leading us to hypothesize that reactivation of VZV could be a cause for RHS as well as Bell's palsy [71].
Conclusion
According to the vaccine study literature, adverse effects have always been part of the mass vaccination strategy, but ultimately the desired effects of the vaccination are more significant. Side effects of COVID-19 vaccination have been reported more frequently in people with a history of immune-related diseases or who are more sensitive to age and physiological conditions. The most important and most common complications are cerebral venous sinus thrombosis (more about AstraZeneca), transverse myelitis (more about Pfizer, Moderna, AstraZeneca, and Johnson & Johnson), Bell's palsy (more about Pfizer, Moderna, AstraZeneca), GBS (more about Pfizer, AstraZeneca, and Johnson & Johnson), and the first manifestation of MS (more about Pfizer). Finally, discovering whether these disorders are accidental or whether the vaccine is the main cause of them requires future studies, ongoing efforts to gather evidence, and long-term monitoring.
Availability of data and materials
Not applicable.
References
Garg RK, Paliwal VK. Spectrum of neurological complications following COVID-19 vaccination. Neurol Sci. 2021. https://doi.org/10.1007/s10072-021-05662-9.
Article
PubMed
PubMed Central
Google Scholar
who.int. https://covid19.who.int/mapFilter=deaths. Accessed 13 Novr 2022
Nagy A, Alhatlani B. An overview of current COVID-19 vaccine platforms. Comput Struct Biotechnol J. 2021;19:2508–17.
Article
CAS
PubMed
PubMed Central
Google Scholar
Abraham G, Bhalala OG, de Bakker PI, Ripatti S, Inouye M. Towards a molecular systems model of coronary artery disease. Curr Cardiol Rep. 2014;16(6):1–10.
Article
Google Scholar
Al Khames Aga QA, Alkhaffaf WH, Hatem TH, Nassir KF, Batineh Y, Dahham AT, Shaban D, Al Khames Aga LA, Agha MY, Traqchi M. Safety of COVID-19 vaccines. J Med Virol. 2021;93(12):6588–94.
Article
CAS
PubMed
PubMed Central
Google Scholar
Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. Autoimmun Rev. 2014;13(3):215–24.
Article
PubMed
Google Scholar
Dutta S, Kaur R, Charan J, Bhardwaj P, Ambwani SR, Babu S, Goyal JP, Haque M. Analysis of neurological adverse events reported in VigiBase from COVID-19 vaccines. Cureus. 2022. https://doi.org/10.7759/cureus.21376.
Article
PubMed
PubMed Central
Google Scholar
Finsterer J. Neurological side effects of SARS-CoV-2 vaccinations. Acta Neurol Scand. 2022;145(1):5–9.
Article
CAS
PubMed
Google Scholar
Ismail II, Salama S. A systematic review of cases of CNS demyelination following COVID-19 vaccination. J Neuroimmunol. 2022;362: 577765.
Article
CAS
PubMed
Google Scholar
Assiri SA, Althaqafi RM, Alswat K, Alghamdi AA, Alomairi NE, Nemenqani DM, Ibrahim ZS, Elkady A. Post COVID-19 vaccination-associated neurological complications. Neuropsychiatr Dis Treat. 2022;18:137.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ghiasi N, Valizadeh R, Arabsorkhi M, Hoseyni TS, Esfandiari K, Sadighpour T, Jahantigh HR. Efficacy and side effects of Sputnik V, Sinopharm and AstraZeneca vaccines to stop COVID-19; a review and discussion. Immunopathologia Persa. 2021;7(2):31.
Article
Google Scholar
Saeed BQ, Al-Shahrabi R, Alhaj SS, Alkokhardi ZM, Adrees AO. Side effects and perceptions following Sinopharm COVID-19 vaccination. Int J Infect Dis. 2021;111:219–26.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhang Y, Zeng G, Pan H, Li C, Hu Y, Chu K, Han W, Chen Z, Tang R, Yin W. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021;21(2):181–92.
Article
CAS
PubMed
Google Scholar
Kadyrova I, Yegorov S, Negmetzhanov B, Kolesnikova Y, Kolesnichenko S, Korshukov I, Baiken Y, Matkarimov B, Miller MS, Hortelano GH. Sputnik-V reactogenicity and immunogenicity in the blood and mucosa: a prospective cohort study. medRxiv. 2022. https://doi.org/10.1038/s41598-022-17514-3.
Article
Google Scholar
Cao L, Ren L. Acute disseminated encephalomyelitis after severe acute respiratory syndrome coronavirus 2 vaccination: a case report. Acta Neurol Belg. 2021;122(3):793–5.
Article
PubMed
PubMed Central
Google Scholar
Erdem NŞ, Demirci S, Özel T, Mamadova K, Karaali K, Çelik HT, Uslu FI, Özkaynak SS. Acute transverse myelitis after inactivated COVID-19 vaccine. Ideggyogyaszati Szemle. 2021;74(7–08):273–6.
Article
PubMed
Google Scholar
Khan E, Shrestha AK, Colantonio MA, Liberio RN, Sriwastava S. Acute transverse myelitis following SARS-CoV-2 vaccination: a case report and review of literature. J Neurol. 2021;269(3):1121–32.
Article
PubMed
PubMed Central
Google Scholar
Malhotra HS, Gupta P, Prabhu V, Garg RK, Dandu H, Agarwal V. COVID-19 vaccination-associated myelitis. QJM: An Int J Med. 2021. https://doi.org/10.1093/qjmed/hcab069.
Article
Google Scholar
Corrêa DG, Cañete LAQ, Dos Santos GAC, de Oliveira RV, Brandão CO, da Cruz Jr LCH. Neurological symptoms and neuroimaging alterations related with COVID-19 vaccine: Cause or coincidence? Clin Imaging. 2021;80:348–52.
Article
PubMed
PubMed Central
Google Scholar
Ozgen Kenangil G, Ari BC, Guler C, Demir MK. Acute disseminated encephalomyelitis-like presentation after an inactivated coronavirus vaccine. Acta Neurol Belg. 2021;121(4):1089–91.
Article
PubMed
PubMed Central
Google Scholar
Chen S, Fan X-R, He S, Zhang J-W, Li S-J. Watch out for neuromyelitis optica spectrum disorder after inactivated virus vaccination for COVID-19. Neurol Sci. 2021;42(9):3537–9.
Article
PubMed
PubMed Central
Google Scholar
Seyed Ahadi M, Ghadiri F, Naser Moghadasi A. Acute attack in a patient with multiple sclerosis 2 days after COVID vaccination: a case report. Acta Neurol Belg. 2021. https://doi.org/10.1007/s13760-021-01775-2.
Article
PubMed
PubMed Central
Google Scholar
Burrows A, Bartholomew T, Rudd J, Walker D. Sequential contralateral facial nerve palsies following COVID-19 vaccination first and second doses. BMJ Case Reports CP. 2021;14(7): e243829.
Article
Google Scholar
Ercoli T, Lutzoni L, Orofino G, Muroni A, Defazio G. Functional neurological disorder after COVID-19 vaccination. Neurol Sci. 2021;42(10):3989–90.
Article
PubMed
PubMed Central
Google Scholar
Ish S, Ish P. Facial nerve palsy after COVID-19 vaccination–A rare association or a coincidence. Indian J Ophthalmol. 2021;69(9):2550.
Article
PubMed
PubMed Central
Google Scholar
Ekizoglu E, Gezegen H, Yalınay Dikmen P, Orhan EK, Ertaş M, Baykan B (2021) The characteristics of COVID-19 vaccine-related headache: Clues gathered from the healthcare personnel in the pandemic. Cephalalgia. 42(4–5):366–75.
PubMed
PubMed Central
Google Scholar
Schulz JB, Berlit P, Diener HC, Gerloff C, Greinacher A, Klein C, Petzold GC, Piccininni M, Poli S, Röhrig R. COVID-19 vaccine-associated cerebral venous thrombosis in Germany. Ann Neurol. 2021;90(4):627–39.
Article
CAS
PubMed
PubMed Central
Google Scholar
Iba T, Levy JH, Warkentin TE. Recognizing vaccine-induced immune thrombotic thrombocytopenia. Crit Care Med. 2022;50(1): e80.
Article
CAS
PubMed
Google Scholar
McGonagle D, De Marco G, Bridgewood C. Mechanisms of immunothrombosis in vaccine-induced thrombotic thrombocytopenia (VITT) compared to natural SARS-CoV-2 infection. J Autoimmun. 2021;121: 102662.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bourguignon A, Arnold DM, Warkentin TE, Smith JW, Pannu T, Shrum JM, Al Maqrashi ZA, Shroff A, Lessard M-C, Blais N. Adjunct immune globulin for vaccine-induced immune thrombotic thrombocytopenia. New Engl J Med. 2021;385(8):720–8.
Article
CAS
PubMed
Google Scholar
Clark RT, Johnson L, Billotti J, Foulds G, Ketels T, Heard K, Hynes EC. Early outcomes of bivalirudin therapy for thrombotic thrombocytopenia and cerebral venous sinus thrombosis after Ad26. COV2.S vaccination. Ann Emergency Med. 2021;78(4):511–4.
Article
Google Scholar
D’agostino V, Caranci F, Negro A, Piscitelli V, Tuccillo B, Fasano F, Sirabella G, Marano I, Granata V, Grassi R. A rare case of cerebral venous thrombosis and disseminated intravascular coagulation temporally associated to the COVID-19 vaccine administration. J Personal Med. 2021;11(4):285.
Article
Google Scholar
Franchini M, Testa S, Pezzo M, Glingani C, Caruso B, Terenziani I, Pognani C, Bellometti SA, Castelli G. Cerebral venous thrombosis and thrombocytopenia post-COVID-19 vaccination. Thromb Res. 2021;202:182–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
García-Azorín D, Do TP, Gantenbein AR, Hansen JM, Souza MNP, Obermann M, Pohl H, Schankin CJ, Schytz HW, Sinclair A. Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis. J Headache Pain. 2021;22(1):1–5.
Article
Google Scholar
George G, Friedman KD, Curtis BR, Lind SE. Successful treatment of thrombotic thrombocytopenia with cerebral sinus venous thrombosis following Ad26. COV2. S vaccination. Am J Hematol. 2021;96(8):E301–3.
Article
CAS
PubMed
Google Scholar
Ramdeny S, Lang A, Al-Izzi S, Hung A, Anwar I, Kumar P. Management of a patient with a rare congenital limb malformation syndrome after SARS-CoV-2 vaccine-induced thrombosis and thrombocytopenia (VITT). Br J Haematol. 2021. https://doi.org/10.1111/bjh.17619.
Article
PubMed
PubMed Central
Google Scholar
Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, Goldblatt D, Kotoucek P, Thomas W, Lester W. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. New Engl J Med. 2021;384(23):2202–11.
Article
CAS
PubMed
Google Scholar
Sharifian-Dorche M, Bahmanyar M, Sharifian-Dorche A, Mohammadi P, Nomovi M, Mowla A. Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review. J Neurol Sci. 2021;428: 117607.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gao J-J, Tseng H-P, Lin C-L, Shiu J-S, Lee M-H, Liu C-H. Acute transverse myelitis following COVID-19 vaccination. Vaccines. 2021;9(9):1008.
Article
CAS
PubMed
PubMed Central
Google Scholar
Notghi AA, Atley J, Silva M. Lessons of the month 1: Longitudinal extensive transverse myelitis following AstraZeneca COVID-19 vaccination. Clin Med (Northfield Il). 2021;21(5): e535.
Article
Google Scholar
Pagenkopf C, Südmeyer M. A case of longitudinally extensive transverse myelitis following vaccination against Covid-19. J Neuroimmunol. 2021;358: 577606.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tahir N, Koorapati G, Prasad S, Jeelani HM, Sherchan R, Shrestha J, Shayuk M. SARS-CoV-2 vaccination-induced transverse myelitis. Cureus. 2021. https://doi.org/10.7759/cureus.16624.
Article
PubMed
PubMed Central
Google Scholar
Vegezzi E, Ravaglia S, Buongarzone G, Bini P, Diamanti L, Gastaldi M, Prunetti P, Rognone E, Marchioni E. Acute myelitis and ChAdOx1 nCoV-19 vaccine: casual or causal association? J Neuroimmunol. 2021;359: 577686.
Article
CAS
PubMed
PubMed Central
Google Scholar
Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet. 2021;397(10269):99–111.
Article
CAS
Google Scholar
Allen CM, Ramsamy S, Tarr AW, Tighe PJ, Irving WL, Tanasescu R, Evans JR. Guillain-Barré syndrome variant occurring after SARS-CoV-2 vaccination. Ann Neurol. 2021;90(2):315–8.
Article
CAS
PubMed
Google Scholar
Bonifacio GB, Patel D, Cook S, Purcaru E, Couzins M, Domjan J, Ryan S, Alareed A, Tuohy O, Slaght S. Bilateral facial weakness with paraesthesia variant of Guillain-Barré syndrome following Vaxzevria COVID-19 vaccine. J Neurol Neurosurg Psychiatry. 2021. https://doi.org/10.1136/jnnp-2021-327027.
Article
PubMed
Google Scholar
Hasan T, Khan M, Khan F, Hamza G. Case of Guillain-Barré syndrome following COVID-19 vaccine. BMJ Case Reports CP. 2021;14(6): e243629.
Article
Google Scholar
Kohli S, Varshney M, Mangla S, Jaiswal B, Chhabra PH. Guillain-Barré syndrome after COVID-19 vaccine: should we assume a causal Link? Int J Med Pharm Case Rep: 20-24. 2021. https://doi.org/10.9734/ijmpcr/2021/v14i130124.
Article
Google Scholar
Permezel F, Borojevic B, Lau S, de Boer HH. Acute disseminated encephalomyelitis (ADEM) following recent Oxford/AstraZeneca COVID-19 vaccination. Forensic Sci Med Pathol. 2021. https://doi.org/10.1007/s12024-021-00440-7.
Article
PubMed
PubMed Central
Google Scholar
Bjørnstad-Tuveng TH, Rudjord A, Anker P. Fatal cerebral haemorrhage after COVID-19 vaccine. Tidsskrift for Den norske legeforening. 2021. https://doi.org/10.4045/tidsskr.21.0312.
Article
PubMed
Google Scholar
Baldelli L, Amore G, Montini A, Panzera I, Rossi S, Cortelli P, Guarino M, Rinaldi R, D’Angelo R. Hyperacute reversible encephalopathy related to cytokine storm following COVID-19 vaccine. J Neuroimmunol. 2021;358: 577661.
Article
CAS
PubMed
PubMed Central
Google Scholar
Antonio Crespo Burillo J, Martínez CL, Arguedas CG, Pueyo FJM. Amyotrophic neuralgia secondary to Vaxzevria (AstraZeneca) COVID-19 vaccine. Neurologia (Barc, Ed impr). 2021. https://doi.org/10.1016/j.nrleng.2021.05.002.
Article
Google Scholar
Alpalhão M, Filipe P. Herpes Zoster following SARS-CoV-2 vaccination–a series of four cases. J Eur Acad Dermatol Venereol. 2021. https://doi.org/10.1111/jdv.17555.
Article
PubMed
PubMed Central
Google Scholar
Tseng P-T, Chen T-Y, Sun Y-S, Chen Y-W, Chen J-J. The reversible tinnitus and cochleopathy followed first-dose AstraZeneca COVID-19 vaccination. QJM An Int J Med. 2021. https://doi.org/10.1093/qjmed/hcab210.
Article
Google Scholar
Finsterer J, Scorza FA, Scorza CA. Post SARS-CoV-2 vaccination Guillain-Barre syndrome in 19 patients. Clinics. 2021. https://doi.org/10.6061/clinics/2021/e3286.
Article
PubMed
PubMed Central
Google Scholar
Introna A, Caputo F, Santoro C, Guerra T, Ucci M, Mezzapesa DM, Trojano M. Guillain-Barré syndrome after AstraZeneca COVID-19-vaccination: a causal or casual association? Clin Neurol Neurosurg. 2021;208: 106887.
Article
PubMed
PubMed Central
Google Scholar
Jain E, Pandav K, Regmi P, Michel G, Altshuler I. Facial diplegia: a rare, atypical variant of Guillain-Barré syndrome and Ad26. COV2. S Vaccine. Cureus. 2021. https://doi.org/10.7759/cureus.16612.
Article
PubMed
PubMed Central
Google Scholar
Loza AMM, Holroyd KB, Johnson SA, Pilgrim DM, Amato AA. Guillain-Barré syndrome in the placebo and active arms of a COVID-19 vaccine clinical trial: temporal associations do not imply causality. Neurology. 2021;96(22):1052–4.
Article
Google Scholar
Malik B, Kalantary A, Rikabi K, Kunadi A. Pulmonary embolism, transient ischaemic attack and thrombocytopenia after the Johnson & Johnson COVID-19 vaccine. BMJ Case Reports CP. 2021;14(7): e243975.
Article
Google Scholar
Etemadifar M, Sigari AA, Sedaghat N, Salari M, Nouri H. Acute relapse and poor immunization following COVID-19 vaccination in a rituximab-treated multiple sclerosis patient. Hum Vaccin Immunother. 2021;17(10):3481–3.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fan H-T, Lin Y-Y, Chiang W-F, Lin C-Y, Chen M-H, Wu K-A, Chan J-S, Kao Y-H, Shyu H-Y, Hsiao P-J. COVID-19 vaccine-induced encephalitis and status epilepticus. QJM: An Int J Med. 2022. https://doi.org/10.1093/qjmed/hcab335.
Article
Google Scholar
Román GC, Gracia F, Torres A, Palacios A, Gracia K, Harris D. Acute transverse myelitis (ATM): clinical review of 43 patients with COVID-19-associated ATM and 3 post-vaccination ATM serious adverse events with the ChAdOx1 nCoV-19 vaccine (AZD1222). Front Immunol. 2021;12:879.
Article
Google Scholar
Ozonoff A, Nanishi E, Levy O. Bell’s palsy and SARS-CoV-2 vaccines. Lancet Infect Dis. 2021;21(4):450–2.
Article
CAS
PubMed
PubMed Central
Google Scholar
Waheed W, Carey ME, Tandan SR, Tandan R. Post COVID-19 vaccine small fiber neuropathy. Muscle Nerve. 2021;64(1):E1.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dyer O. Covid-19: Regulators warn that rare Guillain-Barré cases may link to J&J and AstraZeneca vaccines. Br Med J Publ Gr. 2021. https://doi.org/10.1136/bmj.n1786.
Article
Google Scholar
Keir G, Maria NI, Kirsch CF. Unique imaging findings of neurologic phantosmia following Pfizer-BioNtech COVID-19 vaccination: a case report. Top Magn Reson Imaging. 2021;30(3):133–7.
Article
PubMed
Google Scholar
Santovito LS, Pinna G. Acute reduction of visual acuity and visual field after Pfizer-BioNTech COVID-19 vaccine 2nd dose: a case report. Inflammation Res. 2021;70(9):931–3.
Article
CAS
Google Scholar
Parrino D, Frosolini A, Gallo C, De Siati RD, Spinato G, de Filippis C. Tinnitus following COVID-19 vaccination: report of three cases. Int J Audiol. 2021. https://doi.org/10.1080/14992027.2021.1931969.
Article
PubMed
Google Scholar
Wichova H, Miller ME, Derebery MJ. Otologic manifestations after COVID-19 vaccination: the house ear clinic experience. Otol Neurotol. 2021;42(9): e1213.
Article
PubMed
PubMed Central
Google Scholar
Žorić L, Rajović-Mrkić I, Čolak E, Mirić D, Kisić B. Optic neuritis in a patient with seropositive myelin oligodendrocyte glycoprotein antibody during the post-COVID-19 period. Int Med Case Rep J. 2021;14:349.
Article
PubMed
PubMed Central
Google Scholar
Woo CJ, Chou OHI, Cheung BMY. Ramsay Hunt syndrome following COVID-19 vaccination. Postgrad Med J. 2022. https://doi.org/10.1136/postgradmedj-2021-141022.
Article
PubMed
Google Scholar
McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa D, Tyagi A, Desai SR, French LE, Lim HW, Thiers BH. Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases. J Am Acad Dermatol. 2021;85(1):46–55.
Article
CAS
PubMed
PubMed Central
Google Scholar
Göbel CH, Heinze A, Karstedt S, Morscheck M, Tashiro L, Cirkel A, Hamid Q, Halwani R, Temsah M-H, Ziemann M. Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: a multicentre observational cohort study. Brain Commun. 2021;3(3):169.
Article
Google Scholar
Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, Voysey M, Aley PK, Angus B, Babbage G. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. The Lancet. 2020;396(10267):1979–93.
Article
CAS
Google Scholar
Havla J, Schultz Y, Zimmermann H, Hohlfeld R, Danek A, Kümpfel T. First manifestation of multiple sclerosis after immunization with the Pfizer-BioNTech COVID-19 vaccine. J Neurol. 2022;269(1):55–8.
Article
CAS
PubMed
Google Scholar
Khayat-Khoei M, Bhattacharyya S, Katz J, Harrison D, Tauhid S, Bruso P, Houtchens MK, Edwards KR, Bakshi R. COVID-19 mRNA vaccination leading to CNS inflammation: a case series. J Neurol. 2021. https://doi.org/10.1007/s00415-021-10780-7.
Article
PubMed
PubMed Central
Google Scholar
Watad A, De Marco G, Mahajna H, Druyan A, Eltity M, Hijazi N, Haddad A, Elias M, Zisman D, Naffaa ME. Immune-mediated disease flares or new-onset disease in 27 subjects following mRNA/DNA SARS-CoV-2 vaccination. Vaccines. 2021;9(5):435.
Article
CAS
PubMed
PubMed Central
Google Scholar
Alshararni A. Acute transverse myelitis associated with COVID-19 vaccine: a case report. Int J Res Pharma Sci. 2021;12:2083–7.
Article
CAS
Google Scholar
McLean P, Trefts L. Transverse myelitis 48 hours after the administration of an mRNA COVID 19 vaccine. Neuroimmunology Reports. 2021;1: 100019.
Article
CAS
PubMed Central
Google Scholar
Finsterer J. Exacerbating Guillain-Barré Syndrome Eight Days after vector-based COVID-19 vaccination. Case Rep Infect Dis. 2021. https://doi.org/10.1155/2021/3619131.
Article
PubMed
PubMed Central
Google Scholar
Ogbebor O, Seth H, Min Z, Bhanot N. Guillain-Barré syndrome following the first dose of SARS-CoV-2 vaccine: a temporal occurrence, not a causal association. IDCases. 2021;24: e01143.
Article
CAS
PubMed
PubMed Central
Google Scholar
Razok A, Shams A, Almeer A, Zahid M. Post-COVID-19 vaccine Guillain-Barré syndrome; first reported case from Qatar. Ann Med Surg. 2021;67: 102540.
Article
Google Scholar
Waheed S, Bayas A, Hindi F, Rizvi Z, Espinosa PS. Neurological complications of COVID-19: Guillain-Barre syndrome following Pfizer COVID-19 vaccine. Cureus. 2021. https://doi.org/10.7759/cureus.13426.
Article
PubMed
PubMed Central
Google Scholar
de Terreros Caro GG, Díaz SG, Alé MP, Gimeno MM. Bell’s palsy following COVID-19 vaccination: a case report. Neurologia (Barcelona, Spain). 2021. https://doi.org/10.1016/j.nrleng.2021.04.002.
Article
Google Scholar
Obermann M, Krasniqi M, Ewers N, Fayad J, Haeberle U. Bell’s palsy following COVID-19 vaccination with high CSF antibody response. Neurol Sci. 2021;42(11):4397–9.
Article
PubMed
PubMed Central
Google Scholar
Repajic M, Lai XL, Xu P, Liu A. Bell’s Palsy after second dose of Pfizer COVID-19 vaccination in a patient with history of recurrent Bell’s palsy. Brain Behav Immun Health. 2021;13: 100217.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vogrig A, Janes F, Gigli GL, Curcio F, Del Negro I, D’Agostini S, Fabris M, Valente M. Acute disseminated encephalomyelitis after SARS-CoV-2 vaccination. Clin Neurol Neurosurg. 2021;208: 106839.
Article
PubMed
PubMed Central
Google Scholar
Konstantinidis I, Tsakiropoulou E, Hähner A, de With K, Poulas K, Hummel T. Olfactory dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Int Forum Allergy Rhinol. 2021. https://doi.org/10.1002/alr.22809.
Article
PubMed
PubMed Central
Google Scholar
Ahmed SH, Waseem S, Shaikh TG, Qadir NA, Siddiqui SA, Ullah I, Waris A, Yousaf Z. SARS-CoV-2 vaccine-associated-tinnitus: a review. Ann Med Surg. 2022;75:103293.
Article
Google Scholar
Reyes-Capo DP, Stevens SM, Cavuoto KM. Acute abducens nerve palsy following COVID-19 vaccination. J Am Assoc Pediatr Ophthalmol Strabismus. 2021;25(5):302–3.
Article
Google Scholar
Chiu H-H, Wei K-C, Chen A, Wang W-H. Herpes zoster following COVID-19 vaccine: a report of three cases. QJM: An Int J Med. 2021;114(7):531–2.
Article
CAS
Google Scholar
Rodríguez-Jiménez P, Chicharro P, Cabrera L-M, Seguí M, Morales-Caballero Á, Llamas-Velasco M, Sánchez-Pérez J. Varicella-zoster virus reactivation after SARS-CoV-2 BNT162b2 mRNA vaccination: report of 5 cases. JAAD Case Rep. 2021;12:58–9.
Article
PubMed
PubMed Central
Google Scholar
Salinas MR, Dieppa M. Transient akathisia after the SARS-Cov-2 vaccine. Clin Park Relat Disord. 2021;4: 100098.
PubMed
PubMed Central
Google Scholar
Finsterer J, Redzic Z. Symptomatic peduncular, cavernous bleeding following SARS-CoV-2 vaccination induced immune thrombocytopenia. Brain Hemorrhages. 2021;2(4):169–71.
Article
CAS
PubMed
PubMed Central
Google Scholar
Blauenfeldt RA, Kristensen SR, Ernstsen SL, Kristensen CCH, Simonsen CZ, Hvas AM. Thrombocytopenia with acute ischemic stroke and bleeding in a patient newly vaccinated with an adenoviral vector-based COVID-19 vaccine. J Thromb Haemost. 2021;19(7):1771–5.
Article
CAS
PubMed
Google Scholar
Fitzsimmons W, Nance CS. Sudden onset of myelitis after COVID-19 vaccination: an under-recognized severe rare adverse event. SSRN. 2021. https://doi.org/10.2139/ssrn.3841558.
Article
Google Scholar
Martin-Villares C, Vazquez-Feito A, Gonzalez-Gimeno M, de la Nogal-Fernandez B. Bell’s palsy following a single dose of mRNA SARS-CoV-2 vaccine: a case report. J Neurol. 2022;269(1):47–8.
Article
CAS
PubMed
Google Scholar
Al-Mashdali AF, Ata YM, Sadik N. Post-COVID-19 vaccine acute hyperactive encephalopathy with dramatic response to methylprednisolone: a case report. Ann Med Surg. 2021;69: 102803.
Article
Google Scholar
Channa L, Torre K, Rothe M. Herpes zoster reactivation after mRNA-1273 (Moderna) SARS-CoV-2 vaccination. JAAD Case Rep. 2021;15:60–1.
Article
PubMed
PubMed Central
Google Scholar
Liu BD, Ugolini C, Jha P. Two cases of post-Moderna COVID-19 vaccine encephalopathy associated with nonconvulsive status epilepticus. Cureus. 2021. https://doi.org/10.7759/cureus.16172.
Article
PubMed
PubMed Central
Google Scholar
Šín R, Štruncová D. Status epilepticus as a complication after COVID-19 mRNA-1273 vaccine: a case report. World J Clin Cases. 2021;9(24):7218.
Article
PubMed
PubMed Central
Google Scholar
Athyros VG, Doumas M. A possible case of hypertensive crisis with intracranial haemorrhage after an mRNA anti-COVID-19 vaccine. Angiology. 2022;73(1):87–87.
Article
CAS
PubMed
Google Scholar
Download references
Acknowledgements
Not applicable.
Funding
Not applicable.
Author information
Authors and Affiliations
Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, P.O.Box 76135-133, Kerman, Islamic Republic of Iran
Roya Hosseini & Nayere Askari
Immunoregulation Research Center, Shahed University, Tehran, Islamic Republic of Iran
Nayere Askari
Contributions
RH: carried out the searched publications, classified the documents, and wrote the manuscript draft. NA: supervised the study and reviewed the manuscript. All authors read and approved the final manuscript.
Corresponding author
Correspondence to Nayere Askari.
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Reprints and Permissions
About this article
Verify currency and authenticity via CrossMark
Cite this article
Hosseini, R., Askari, N. A review of neurological side effects of COVID-19 vaccination. Eur J Med Res 28, 102 (2023). https://doi.org/10.1186/s40001-023-00992-0
Download citation
Received
18 June 2022
Accepted
04 January 2023
Published
25 February 2023
DOI
