We aimed to review the available reports of psychiatric adverse reactions to COVID vaccines. Electronic databases such as PubMed and Google scholar were combed to identify relevant reports. We found a total of 11 reports describing 14 cases of psychiatric reactions; these were mostlyaltered mental states, psychosis, mania, depression, and functional neurological disorder. The index case was commonly a young or middle-aged adult. All reports pertained to the use of either mRNA or vector-based vaccines. Symptom onset was within 10 days of vaccination in all cases; as such, this seems to be a high-risk period warranting vigilance.
Two patients had been vaccinated with the BNT162b2 mRNA vaccine. Similarly, Flannery et al. reported acute psychosis due to encephalitis following BNT162b2 mRNA vaccination (Flannery et al. 2021). One of our patients had been vaccinated with Ad26.COV2.S adenoviral vector vaccine. To our knowledge, this is the first report of a psychotic disorder following this specific vaccine, although there are reports of psychotic symptoms after another adenoviral vector vaccine (ChAdOx1 nCoV-19 vaccine) (Grover et al. 2022, Takata et al. 2021).
All our cases of psychotic disorders described in these reports involved individuals with no personal or family history of mental illness. The psychotic symptoms began within 2 weeks after administration of the COVID-19 vaccine. We observed that all the patients had paranoid delusions and one of them also had hallucinations.
All of our patients complained of headaches within five days of vaccination with the COVID-19 vaccine, considering that two of the patients who had received the mRNA vaccine also had paraesthesia and one of them also had syncope. In two cases (mRNA and vector vaccine) the neurological and psychotic symptoms started simultaneously, and in one case (mRNA vaccine) the neurological symptoms preceded the psychotic symptoms.
A 31-year-old, single Hispanic male without past medical or psychiatric history, was brought to the emergency room by police because of erratic and bizarre behavior. He was found to be anxious, guarded, superficial and grandiose. He reported becoming ‘clairvoyant’, being able to talk with dead people, hearing ‘people drumming outside his house’ and the constant voice of a co-worker whom he believed to be a paramour- it was later confirmed that there was no romantic relationship. All these symptoms began one month ago, after receiving the first dose of an mRNA-based COVID-19 vaccine, and markedly worsened three weeks later after receiving the second dose. Previously, he was asymptomatic, working full-time as an office manager. Although functional in adolescence `and adulthood, he described himself as a loner, with an inclination to overly spiritual ideas, and able to communicate directly with God. He had a few close friends and romantic relationships.
The patient was a 20-year-old single woman in her final year of technical college, with no significant medical or psychiatric history and no family psychiatric history. She was brought to the emergency department by her family after having a single seizure-like episode at home preceded by a 4-week history of anxiety, sleep disturbance, and behavioral changes that started a few days after receiving the second dose of COVID-19 vaccine.
The patient reported feeling anxious and restless, having a reduced appetite, and hearing terrifying voices and seeing random people staring at her. She also complained of interrupted sleep with frequent nightmares and sleep terror. At the emergency department, the patient was anxious but settled and cooperative.
While she was in the inpatient unit, she was noted to be aggressive against male hospital staff, which was clearly driven by her paranoid delusional beliefs. The olanzapine dose was gradually titrated to 25 mg/d. She became fully oriented to time, place, and person after a few days, but she continued to complain of auditory and visual hallucinations. Fourteen days later, her paranoia and suspiciousness, aggressiveness, and auditory and visual hallucinations started to improve. She remained in the hospital for a total of 28 days and was discharged home after complete remission of acute psychotic symptoms with some residual symptoms, mainly reduced concentration and motivation.
A female in her 20's presented to the Emergency Department (ED) with a chief complaint of urinary frequency 1 week after receiving her first dose of the Pfizer-BioNTech COVID-19 vaccine (Figure 1). The patient's family stated she had increasingly frequent bouts of anxiety, decreased mentally acuity, insomnia, and a fixation that she suffered from irritable bowels and kidney disease. She displayed waxing and waning hypochondriacal delusions that she had contracted COVID-19 and that “her body was shutting down.
The following morning the patient removed her clothing and had a bowel movement on the floor. The constellation of symptoms (spontaneous defecation, catatonia, sudden encephalopathy without metabolic or infectious findings) coupled with the preliminary CSF results and the history of deterioration after SARS-CoV-2 vaccination led to a strong clinical suspicion of an autoimmune-mediated encephalitis driven by the vaccine
A 37-year-old man received the BNT162b2 (Pfizer/BioNTech) mRNA vaccine twice, and experienced fatigue after the first booster shot approximately 6 months prior to presenting at our institution. After the third COVID-19 vaccination half a dose of the mRNA-1273 (Moderna) vaccine he complained of mild headache, a floating sensation, and difficulty concentrating; he did not have fever. Four days after vaccination, he presented with talkativeness, and grandiose delusions, saying that he had won 2 billion yen in horse racing. He also presented with emotional instability, such as crying when saying “Everyone would be happy.”
This was his first psychiatric admission; he had no previous medical history. He exhibited flight of ideas, hyperactivity, distraction, hyperthymia, and religious delusions, such as saying “my child is God.” He displayed a lack of insight and became enraged when his actions were restricted.
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.
A 38-year-old woman was admitted to the Psychiatry of the Hospital Complex of Sorocaba, showing disorganized behavior and aggression. Six months ago, he received the first dose of the mRNA vaccine for COVID-19 and, about 24 hours later, he had systemic adverse effects followed by aggression and delusional thinking of a persecutory nature. She had no previous clinical or psychiatric reports. Previously, it was perfectly functional. We carried out extensive clinical and laboratory investigation and all tests were negative. Several pharmacological therapies with antipsychotics and mood stabilizers were used, but after more than four months of hospitalization, the improvements observed were only in orientation and behavior, remaining with symptoms of psychosis.
A 45-year-old single Caucasian male without past medical and psychiatric history visited the outpatient psychiatric clinic accompanied by his parents because of bizarre behavior and an attempted suicide by hanging in the early morning of the visit day. An outpatient psychiatrist referred him for inpatient treatment due to psychosis and a high risk of self-harm. There is no family history of mental illness to suggest any genetic predisposition to psychiatric morbidity. There were no perinatal complications or neurodevelopmental delays in his infancy. His early life experiences were good; he lived in a full family, as an honest child, without significant traumatic experiences. The patient graduated from secondary school and began working as a worker.
A month before the hospitalization, he received the second dose of the mRNA-based COVID-19 vaccine and immediately developed total insomnia, unreasonable anxiety, and tremor. As a result, he contacted his family doctor who prescribed metoprolol 50 mg a day, phenibut 250 mg a day, zolpidem tartrate 10 mg a day, but this therapy did not help, insomnia and fear remained.
After 2 weeks, he realized that he has been jinxed as he found some white powder under the carpet in his apartment. From that moment, he became cautious, did not leave the apartment, and reported persecution. On the last day before his visit to the psychiatric clinic, the patient saw a man walking past the windows of his apartment and watching him. The patient described the thoughts in his head as not his own, giving him commands to observe the person on the street. He did not sleep that night and had a strong belief that he should commit suicide. He attached a rope, tried to hang himself, but his father stopped him.
A 26-years old female with a family history of a mother diagnosed with schizophrenia, and no personal medical or psychiatric history, was diagnosed with mild COVID-19 infection by nasopharyngeal and throat swab reverse transcription-polymerase chain reaction (RT-PCR), four days after receiving the second dose of Pfizer-BioNTech COVID-19 vaccine. She was asymptomatic when she received the COVID-19 vaccine. Two weeks later, she presented to the emergency department with chest pain, where physical examination revealed a heart rate of 110/min. A cardiac ultrasound examination showed a pericardial effusion suggestive of pericarditis.
One month after receiving the vaccine, she presented to the psychiatric emergency department with acute psychomotor agitation, incoherent speech and total insomnia evolving for five days. She had no recent history of trauma, and no lifetime history of substance use.
She was admitted to our psychiatric unit, where psychiatric examination revealed severe anxiety, delusions of persecution and reference, auditory hallucinations, disorganized speech and behavior. The patient had no delirium symptoms and a lack of insight.
On the seventh day of admission, while her discharge has been planned and discussed with the family, she reported the onset of severe asthenia with dysphagia. Physical examination found fever (body temperature of 40 degrees Celsius), tachycardia (heart rate of 123 beats/min), and multiple mouth ulcers. On laboratory tests, she had severe acute kidney failure, proteinuria, high CRP values, and pancytopenia. Chest X-ray showed bilateral pleural effusion. Immune tests identified the presence of antinuclear antibodies. The anti-ENA (extractable nuclear antigen) antibody screen showed strongly positive anti-SSA, anti-Ro52, anti-SSB, as well as weakly positive anti-nucleosome, and anti-histone antibodies. Brain magnetic resonance imaging (MRI) revealed hyperintense signals in the left fronto-parietal lobes and the cerebellum (Fig. 1). Based on these clinical and laboratory evidence, the patient was diagnosed with SLE according to the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria
A 60-year-old African American female patient with previously stable BD1 presented to the office after three weeks of depressed mood, anxiety, and decreased need for sleep. She was observed to have increased energy, impulsivity, labile affect, verbose speech with repetitive phrases, tangential thinking and flight of ideas, paranoia, and ideas of reference, consistent with a mixed episode with psychotic features. She reported that her symptoms began within a week of receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. She denied suicidal and homicidal ideations. Her symptoms were distressing and led her to call off work repeatedly, despite satisfaction with her job.
40-year-old White male patient with previously stable BD1 and attention deficit hyperactivity disorder (ADHD) was voluntarily hospitalized due to a mixed episode with psychotic features. He reported depressed mood, suicidal ideation, and auditory hallucinations encouraging him to kill himself, but denied homicidal ideation. Upon admission, he was observed to have hyperactivity, impulsivity, irritability, flight of ideas, labile affect, pressured and hyperverbal speech, tangential thought processes, limited attention, and poor short- and long-term memory, with limited recall of three objects after five minutes and major historical events. He reported that his symptoms began after receiving the second dose of the Moderna COVID-19 vaccine and subsequently worsened after he discontinued his medications five days prior to admission. He lost his job after a verbal altercation with his boss, prompting him to seek inpatient treatment.
An 18 years old female student, without any past psychiatric (including the substance use disorders) or medical history, with no family history of mental illness, was brought to the emergency by family members for irrelevant talk and bizarre behavior. There was no past history of physical illness or substance use. Exploration of history revealed that the patient was apparently maintaining well before vaccination and there was no apparent psychosocial stressor prior to vaccination, nor did the patient have any vaccine hesitancy. She received her first dose of the vaccine, and within 2–3 h she developed high grade fever with chills, and multiple episodes of loose stools.
As per family members fever subsided the next day, but patient reportedly started to remain anxious. She was not able sleep at night, frequently woke-up, appeared fearful and would appear to be staring in between. She would keep on pacing around and would appear distressed. Over the next 3 to 4 days, she started to remain irritable, talk irrelevantly, try to run away from home, voiced delusions of persecution and reference, and reported visual hallucinations of seeing Gods and demons.
A 15-year-old boy presented to the emergency department of our hospital with the chief complaint of agitation, involuntary limb stretching, and screaming 2 days after receiving his second dose of the BNT162B2 vaccine. He was healthy without any specific medical history before the vaccination.
After admission, he was observed to demonstrate bizarre behaviors, including sitting up and lying down frequently and taking up the mannerism of praying in bed. We also noted auditory hallucinations and delusions.
A 42-year-old male was admitted to the psychiatric emergency department five days after being vaccinated with the first dose of the BNT162b2 mRNA vaccine with complaints of irritability and sleeplessness. Although the patient did not have any symptoms outside of weakness on the day of vaccination, the complaints started one day after receiving the vaccine. The patient had delusions that his family was being followed by the deep state and that they were in danger. The patients affect was anxious and the mood was dysphoric. He exhibited a loosening of associations, described persecutory and reference delusions and displayed a lack of insight.
A 57-year-old male was admitted to the psychiatric emergency department with complaints of irritability, sleeplessness, talking to himself and suicidal attempt with thoughts of extinction three days after receiving the second dose of the BNT162b2 mRNA vaccine. While firstly the patient only had local myalgia on the arm on the day of vaccination, psychiatric symptoms started at night on the day he was vaccinated. The patient did not have a history of any diseases that required the use of medication, was vaccinated voluntarily and did have any anxiety about vaccination. Clinical evaluation suggested intact cooperation and orientation while speech output, speed as well as psychomotor activity were increased. The patient was anxious, and his mood was dysphoric. Nihilistic delusions with no insight were recorded.
Ms A is a 45-year-old Asian American woman who presented to the outpatient psychiatry department after having psychosis for 3 months. Her new-onset paranoia and auditory hallucinations began 1 month after receiving her second mRNA-1273 (Moderna) COVID-19 vaccine. She abruptly quit her job of 18 years and stopped eating—losing 56 lb in 4 months. The patient would only get dressed in the dark, believing people could see her in her closet or bathroom behind a closed door. She would pace all day and stopped doing the household chores she had done for years. She would wake her husband in the middle of the night trying to convince him that the neighbors were going to hurt her and were breaking into their home. She became angry when he tried to convince her these things were not real. Due to this irrational fear, she would sleep only 2 to 3 hours per night and no longer slept in the bedroom, preferring to lock herself in the bathroom to sleep. She heard whispers of people talking about her and would carry on full conversations with them. She would only do this in a room alone with the door closed. Family would ask her who she was talking to, and she would again become angry. She told the clinician that they had to explain to her family that these people were real and there was nothing wrong with her. Her affect was full, and psychomotor activity was unremarkable, as was her speech rate.
A 40-year female, unmarried, post-graduate, and unemployed, who was premorbidly well adjusted, with no past or family history of mental disorder, with no history of COVID-19 infection, was vaccinated with 1st dose of COVID-19 vaccine (Covishield) in mid-2021. On the evening of the day of the vaccination, she started complaining of headache associated with palpitations and discomfort in the chest. On the same night, she was not able to sleep properly. From the next day, she was observed to be fearful and restless. On the second night, she was also unable to sleep and kept pacing throughout the night. From the next day, she started expressing fearfulness and suspiciousness. On the third day, she was seen by a psychiatrist, and a diagnosis of acute transient psychotic disorder was considered and started on tablet olanzapine 5 mg per day. However, her symptoms kept worsening, and from the fourth day, additionally started voicing delusions of persecution against her sister-in-law (i.e., planning to harm her) and reported commanding auditory hallucinations which were present for most part of the day, and were very distressing to the patient.
The patient was a 52-year-old woman with a history of bipolar disorder for the last 11 years, which was well controlled for the last 7 years on her regimen of medications that included haloperidol 5 mg/d, quetiapine 50 mg/d, and trihexyphenidyl 6 mg/d. She received her first dose of COVID-19 vaccine (ChAdOx1-S/nCoV-19 vaccine) in June 2021, following which she developed mild fever and myalgia that subsided in 2 to 3 days. During this period, she started having reduced sleep at night with no tiredness in the morning. She also became hyperactive, over talkative, demanding, and irritable. Her confidence increased, and she expressed big plans.
This patient experienced a rapid relapse of her bipolar mania within a few days after receiving the first dose of COVID-19 vaccine (ChAdOx1-S/nCoV-19 vaccine). Temporal association in the absence of any other life stressors indicates that manic relapse in our patient is probably related to the vaccination. Side effects of COVID-19 vaccinations in individuals with bipolar disorder have so far not been researched.5 The most probable explanation for manic relapse in the present case could be that the immunologic response following vaccination might have triggered manic symptoms by creating a hyperinflammatory state. Previous research has shown the potential link between elevated levels of inflammatory markers and the onset of mania.
The case was a 26-year-old man with a history of Down syndrome with moderately good autonomy for daily routine tasks. The patient, who presented hypothyroidism at 10 years old and schizophrenia at 15 years old, was doing well before the vaccination and received his first dose of the BNT162b2mRNA vaccine. Twenty-four hours later, he presented depressive symptoms that resolved spontaneously after one week. Then, fifteen days later, the symptoms reappeared, and the episode lasted for 5 weeks.
