Acute Psychosis After Immunization With Whole-Virion Inactivated COVID-19 Vaccine; A Case Report From Central India

To the Editors

The beginning of the coronavirus disease 2019 (COVID-19) pandemic was associated with the beginning of a simultaneous mental health pandemic. Increasing restrictions on travel, limited social interaction, fear of getting infected, and isolation at quarantine centers and hospitals were some of the reasons for the worsening of mental health status.¹ Studies have reported increased rates of neuropsychiatric manifestations in people affected with COVID-19. This includes depression (12.9%), anxiety disorders (19.1%), sleep disorders (27.4%), posttraumatic stress (15.7%), and cognitive impairment (20.2%), among others.² A recent review also reports the occurrence of psychiatric adverse events like altered mental status, psychosis, depression, mania, and functional neurological disorders after immunization with the COVID vaccine.³ Although the data regarding such adverse events are scarce, the existing literature reports these adverse events with messenger RNA (mRNA)–based^4–6 and viral vector COVID vaccines.^7–10 Here we report the case of a 17-year-old adolescent girl who developed psychosis after the second dose of the Covaxin vaccine, a whole-virion inactivated SARS-CoV-2 antigen vaccine. The patient and her parents provided consent for publication of this case report.

CASE REPORT

A 17-year-old adolescent girl presented at the mental health clinic of our referral hospital with an acute onset illness of 1-month duration. The presenting complaints were being restless, fearful, suspicious, talking to herself, poor self-care, disinhibited behavior, decreased food intake, and decreased sleep of 1-month duration. These symptoms appeared within 48 hours of receiving the second dose of the COVID vaccine at a primary health center in February 2022. There was no history of fever postvaccination, and no history of mental illness or substance use was reported. No adverse events were reported after the first dose of the vaccine received in January 2022. There was no history of any mental illness in the family. On examination, she was uncooperative, restless, and fearful, and hallucinatory behavior was observed. She refused to answer questions. No neurological abnormalities were observed. She was rated on Brief Psychiatric Rating Scale with a total score of 55. Investigations including complete blood count, liver function test, renal function tests, serum electrolytes, and thyroid profile were within normal limits for her age. Rapid antigen test screening for COVID-19 was negative. Computed tomography scan of the brain (plain and contrast) did not reveal any abnormality. After discussion with the parents, it was decided to manage the patient on an outpatient basis. The patient was started on olanzapine (5 mg) and clonazepam (0.5 mg) PRN and was followed up after 2 weeks. On follow-up, the patient had shown improvement in self-care, social interaction, hallucinatory behavior, and sleep. She remained fearful and reported auditory hallucinations in the past, which had decreased in severity. Brief Psychiatric Rating Scale score during this visit was 39. Because there was a significant improvement, olanzapine (5 mg) was continued, and a follow-up after 2 weeks was scheduled. On 4-week follow-up, the patient reported that auditory hallucinations had stopped; improvement was noted in other symptoms like fearfulness, self-care, and social interaction; and she was performing routine activities. Brief Psychiatric Rating Scale score had further reduced to 21. She was advised to continue olanzapine and follow up regularly.

DISCUSSION

India started the COVID-19 vaccination program for adolescents aged 15 to 17 years January 3, 2022. Covaxin vaccine, a whole-virion inactivated SARS-CoV-2 antigen vaccine, is the only approved vaccine for this age group. To date, more than 100 million doses of vaccine have been given across the country to children of this age group.¹¹

Psychiatric adverse events following the COVID-19 vaccine appear to be a rare occurrence. Adverse events like psychosis,^4,5,9 mania,⁶ depression,⁷ acute confusional state,⁸ and functional neurological disorders¹⁰ have been previously reported. These adverse events were reported in the adult population with mRNA and viral vector vaccines.³ To the best of our knowledge, this is the first case report of a whole-virion inactivated SARS-CoV-2 vaccine-associated psychiatric adverse effects in an individual younger than 18 years.

Messenger RNA vaccines are associated with fewer systemic adverse events when compared with viral vector vaccines.¹² It is hypothesized that inoculation with the COVID-19 vaccine may result in a proinflammatory response and an autoimmune reaction, which may lead to autoimmune encephalitis.⁹ The immunogenic response due to the vaccine is less than that of SARS-CoV-2 infection itself.³ However, it may be severe enough to trigger a cytokine storm. Elevated levels of interleukin (IL)-1, IL-6, IL-10, and tumor necrosis factor α in turn affect the levels of monoamine neurotransmitters and dysfunction of N-methyl-D-aspartate receptors. This leads to an increased level of dopamine and may trigger psychiatric manifestations in the affected individuals.¹³

Precipitation of symptoms within 48 hours of inoculation, exclusion of other probable causes, and absence of genetic predisposition to mental illness indicate the psychiatric adverse event may be related to the vaccine. This case report presents a rare adverse event associated with the whole-virion inactivated SARS-CoV-2 antigen vaccine. This by itself should not deter individuals from getting vaccinated against a deadly infection that brought the world to a standstill. This should rather generate awareness and accentuate surveillance for the possible adverse events postvaccination.

Avinash Shukla, MBBS, DPM, DNB (Psychiatry)
District Hospital, Raipur
Chhattisgarh, India
dravinashcip@gmail.com
Neethu K. Nandan, MBBS
All India Institute of Medical Sciences, Raipur
Chhattisgarh, India
Lokesh Kumar Singh, MBBS, MD, DPM
All India Institute of Medical Sciences, Raipur
Chhattisgarh, India