Indian COVID-19 Vaccine Recipients may have Serious Neurological and Psychiatric Adverse Events

In India, the vaccination drive against coronavirus disease 2019 (COVID-19) was rolled out on January 18, 2021. As per COWIN (Covid Vaccine Intelligence Network) platform (owned by the Government of India), 1,97, 34, 08,500 vaccine doses had been administered till June 28, 2022 with the majority receiving the COVISHIELD™ vaccine.

COVID-19 vaccination may be associated with several types of adverse events. Commonly reported post-vaccination adverse events are pain and/or tenderness at the injection site, headache, dizziness, nausea and vomiting, fever, chills, itching and rashes at the injection site, myalgia, and/or arthralgia. These adverse events are mild and self-limiting.

India lacks a robust Adverse Events Following Immunization (AEFI) reporting system. Consequentially, comprehensive data on neurological and psychiatric serious adverse events following COVID-19 vaccination are sparse. Garg et al systematically reviewed all published case reports and case series describing neurological and psychiatric serious adverse events among COVID-19 vaccine recipients from India.

Their systematic review noted that till June 27, 2022, 136 instances of neurological and psychiatric serious adverse events occurred among 2000 million COVID-19 vaccine recipients in India. These neurological or psychiatric events had been described in 64 isolated case reports or case series.

In six isolated instances, psychiatric adverse events had also been reported. Considering the enormity of the Indian COVID-19 vaccination drive, the reported neurological and psychiatric events appear minuscule.

They found ten published Indian cases of potentially life-threatening VITT, all of whom presented with cerebral venous sinus thrombosis. Earlier, a report from the Ministry of Health and Family Welfare (Government of India) had verified 26 cases of cerebral thromboembolism after an in-depth review of 498 serious adverse events. In all, thromboembolic events had occurred following administration of the COVISHIELD vaccine. The Indian AEFI Committee had then estimated the risk of thromboembolic events following COVISHIELD vaccination at 0.61 cases/million doses. VITT generally responds well to early treatment with intravenous immunoglobulins. For anti-coagulation, non-heparin anti-coagulants are preferred. Platelet transfusions are avoided.

MOG antibody-associated demyelinating diseases emerged as the most frequent neurological adverse event after COVID-19 vaccination. The majority of these cases had involvement of multiple CNS regions including spinal cord, brainstem, and supratentorial brain and optic nerves. Good improvement was observed with immunotherapy.

Among Indian vaccine recipients, Guillain-Barré syndrome was the most frequent immune-mediated peripheral neuropathy (n = 19). Keh and colleagues analyzed a possible relationship between COVID-19 vaccination and Guillain-Barré syndrome and noted an increased incidence of Guillain-Barré syndrome in the post-COVID-19 vaccination period.

The exact mechanisms, responsible for immune-mediated neurological complications following COVID-19 vaccination, are largely speculative. The phenomenon of molecular mimicry is currently the most accepted mechanism to possibly trigger both post-vaccinal immune-mediated complications. Components of the adenovector-based COVID-19 vaccine can trigger an immune reaction that leads to an unregulated inflammatory cascade damaging the brain and peripheral neurons. In adenovector COVID-19 vaccines, the SARS-CoV-2 spike protein gene, included in replication-deficient chimpanzee adenovirus ChAdOx1, may act as an autoantigen. Adjuvants, added to enhance immune responses, may increase the immune reactivity further.

They also recorded 31 Indian cases of herpes zoster following adenovector-based COVID-19 vaccination. There are conflicting views on whether COVID-19 vaccination triggers herpes zoster or not. In a case-control study, among a cohort of 1,095,086 COVID-19-vaccinated persons, 2204 (0.20%) subjects developed herpes zoster within 60 days of COVID-19 vaccination. In the control group of 1,095,086 unvaccinated persons, 1223 (0.11%) patients had herpes zoster; the difference was statistically significant. Herpes zoster has been more frequently documented following the administration of mRNA vaccines. It is possible that an altered cell-mediated immunity following COVID-19 vaccination leads to the re-activation of latent Varicella-zoster infection within neuronal cells, leading to a clinically manifest herpes zoster.

They reviewed six instances of psychiatric adverse events. In two cases, functional neurological disorders following vaccination were observed. Functional neurological disorders generally resemble a true neurological disorder, such as movement disorder, hemiparesis, paraparesis, sensory manifestations, dizziness, speech disorders, and psychogenic nonepileptic seizures. Wrong information about vaccines on social media, pandemic-associated stress, and enhanced psychological stress was considered reasons responsible for the occurrence of functional neurological disorders in some COVID-19 vaccine recipients.

To conclude, a variety of serious neurological complications have been reported in Indian recipients of COVID-19 vaccine; the overall risk, however, appears minuscule. Immune-mediated central and peripheral neuronal demyelination events were particularly frequent. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders seem to respond well to immunotherapy.

Reference:

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series, Neurology India, Ravindra Kumar Garg, Vimal Paliwal, Hardeep Singh Malhotra, Balendra Pratap Singh, Imran Rizvi, Neeraj Kumar DOI: 10.4103/0028-3886.375420