Introduction
Psychosis refers to a collection of symptoms affecting the mind resulting in some loss of contact with reality. It is characterised by delusions and disorganised thought, behaviour or speech. It is typically triggered by neurological, psychiatric or medical conditions and exacerbated by anxiety and emotional or psychological distress.
Confirming previous studies on trends seen in respiratory diseases, many disorders have increased in occurrence since COVID-19. Notably there was an increased risk of anxiety and depression but this was often short lived and subsided after two months, similar to other respiratory infections. Yet the risk of many neurological disorders such as psychosis, dementia and cognitive deficits (‘brain fog’), was still heightened even 2 years after COVID-19. The delta variant showed an increased rate in diagnosis of neurological disorders than the alpha variant, and the omnicron variants, whilst presenting with a less severe acute illness, maintained a comparable psychosis diagnosis rate to the delta variant. Overall, this article investigates the significance of the association between COVID-19 and new-onset psychosis.
Historical Viral infection and risk of psychosis
The possible link between psychosis and viral disease can be traced back a century to the aftermath of the Spanish flu. In 1918 Karl Menninger detailed a report on patients presenting symptoms of ‘dementia praecox’ and other psychological symptoms such as disturbance and psychomotor confusion. They were admitted to a psychopathic (psychiatric) hospital at the height of the Spanish Flu and Menninger ensured the separation of patients who presented with the psychotic symptoms from those presenting with generalised delirium. In a follow up study in 1926, Menninger observed 50 patients diagnosed with dementia praecox after the influenza outbreak and was surprised to find the majority of patients had completely recovered. This outcome suggested that the effects of this illness-induced psychosis was temporary, which contrasts the Kraepelinian notion that dementia praecox patients were expected to have a deterioration in long term treatment.
An estimated 0.9-4% of individuals exposed to SARS, MERS and COVID-19 developed psychosis or psychotic symptoms according to a literature review by Brown et al. which is significantly higher than the median incidence of 0.015% in the general population. The trend between increased risk of psychosis through exposure to severe respiratory diseases has been previously linked to SARS and MERS, both having the ability to infect the nervous system, providing a possible etiological pathway. However, in those diseases, psychiatric manifestations of depression and anxiety were often associated with the stress of having a life-threatening illness and isolation, whilst mania and psychosis were associated with
steroid use. Regardless, COVID-19 was a more severe disease and led to greater levels of social anxiety and isolation, which would increase risk of psychosis compared to either of those diseases.
Possible etiological pathway linkage
The SARS-CoV-2 virus primarily targeted the lungs which can induce acute respiratory distress syndrome. This can then reduce oxygen supply to the brain and other organs which can cause multiple organ failure. SARS-CoV and SARS-CoV-2 are both neurotropic and would most likely have entered the CNS through the bloodstream. During a cytokine storm, various inflammatory cytokines are produced at a much higher rate than normal. The resulting cell membrane breach compromises the patient’s immune response, enabling the virus to gain access and infect multiple tissues. Injections of cytokines cause human syndromes such as fever, fatigue and sleep disturbances in animals, showing the significance of proinflammatory cytokines in inducing sickness behaviours which is seen during COVID-19.
Patients who suffered severe lung deficiency also exhibited affects to the brain and neural system leading to early symptoms of headaches, mental confusion and psychiatric disorders, which may be an indication of the nervous system's vulnerability to the virus. Despite SARS-CoV-2 scarcely being found in cerebrospinal fluid, the viral induced immune reactions and autoimmunity may provide a pathway by which the virus could have impacted CNS function.
Elderly patients recovering from pneumonia present with delirium or memory deficits which persist over time and may require demanding treatments. Delirium is often provoked by peripheral infection which is associated with systemic inflammation. Neuroinflammation is often a significant component in neurodegenerative disorders and the risk of depressive episodes increases by 60%. In addition, severe respiratory failure with COVID-19 triggers hypoxia (insufficient oxygen) which can affect the brain, even permanently in extreme cases.
Possible cofounders
In order to investigate the significance of COVID-19 and new-onset psychosis, causality must be determined for the association to be plausible. However, assumptions made in several studies targeting association between COVID-19 and new onset psychosis do not meet the Bradford Hill Criteria for strength, consistency, specificity or temporality necessary to determine causality. In order to accurately determine causality, co-founders such as psychosocial factors must be addressed.
The association between psychosis and a variety of psychosocial factors has been extensively researched and these stressors are significant risk factors in exacerbating psychosis. On one hand, patients suffered many social stressors such as isolation due to quarantine, limited information about the novel virus, treatment and misinformation in the media leading to increased anxieties. On the other hand, social stresses have adverse impacts on brain function particularly in dopaminergic signalling which is significant in psychosis.
The side effects of the treatment itself must be considered. During the first phase of the pandemic, many drugs were tested in order to provide a possible treatment to the virus which included antibiotics, antimalarials and corticosteroids. Though antibiotics would be ineffective against a virus the four most frequently prescribed therapeutic solutions during the first wave of the pandemic were azithromycin (50.7%), doxycycline (13.0%), amoxicillin (9.4%), and levofloxacin (6.7%). This is notable as there has been an investigated direct link between antibiotic exposure and psychosis. Antimalarial hydroxychloroquine has a documented link to neuropsychiatric adverse effects as the hydroxychloroquine crosses the blood-brain barrier and can concentrate within the CNS. Despite this it was a promising treatment in the first wave of the pandemic. In addition, previous studies to do with SARS concluded higher doses of corticosteroids were associated with an increased risk of psychosis.
COVID 19 and psychosis - case study
A 42-year old woman was brought to a psychiatric consulting room in July 2020. At the time she was divorced and lived with her 18-year old daughter, who was affected by multiple sclerosis. The patient had no psychiatric conditions and was not on any medication (prescribed or substance abuse) nor a family history with psychiatric disorders. In May 2020, she tested positive for a SARS-Cov-2 oropharyngeal swab and reported a sore throat, fatigue and dry cough. She moved to another house in Rome in order to protect her daughter and stayed isolated for 13 days, after which she gradually recovered without requiring treatment but carried on experiencing anosmia and ageusia. At the psychiatric examination she reported tactile and visual hallucinations in the form of bugs crawling or underneath her skin two weeks after the beginning of the infection. Worried they may infect her daughter she remained isolated and washed her hands several times a day with detergent. She contacted a dermatologist who diagnosed her contact dermatitis and suggested psychiatric intervention. After her psychiatric consultation, she was prescribed 2 mg of risperidone, increasing to 3mg a week later but then gradually reduced to 1mg and once she showed no sign of relapsing she was able to discontinue the medication.
Discussion
This psychosis is an example of the rare Ekbom syndrome and may be an organic delusional parasitosis as it occurred secondary to organic illness despite being younger than the mean age of onset. Like most patients she seeked non-psychiatric help from a dermatologist who was able to identify the psychiatric nature of the condition. Being divorced may have added to mental strains as well as having responsibility for a daughter who was affected by a chronic disease and especially vulnerable to the effects of COVID-19. However, specifics about these factors are uncertain, and so they could have been insignificant. The constant washing may be an effect of the Ekbom disease but can also be a sign of fear of contamination which further suggests the psychosis had stemmed from the anxiety the patient had. It is noteworthy that the patient gradually recovered from COVID-19 with no medical intervention, suggesting that her onset of psychosis was triggered less significantly by physical factors as suggested above but rather by psychosocial factors.
Social and mental contributions
Despite the suggested aetiological pathways it can be argued that mental and social contributions play a more significant role in the development of psychosis and other neurological disorders. An increase in psychosis has been observed after severe viral epidemics not caused by viruses associated with severe acute respiratory syndrome e.g. Ebola and Zika viruses. The causal relationship between intense stress and psychosis suggests that the anxiety experienced during COVID-19 may have caused psychotic symptoms. This stress is applicable to most intense diseases with long-term or wide reaching impacts. Stress induced psychosis lasts for around one month and this longevity is similar to post COVID-19 psychosis as it can be resolved with psychiatric help.
Researchers at Bangor University suggest that the more strictly COVID-19 policies were complied with, the worse their mental health is presently. Generally, social distancing has been linked with depression, anxiety, acute stress, and intrusive thoughts. Confinement has shown to have psychological impacts on people and the lack of sunlight decreases serotonin levels which is associated with emotional disorders. Long term isolation as seen in long lockdowns can then lead to psychological disturbance. The increased usage of screens for at home work or schools can lead to lack of movement and sleep disturbances all of which will impact emotional states. In one study, 53.3% of people reported their level of anxiety to be higher than before the pandemic. All of these can contribute to the development and exacerbation of psychosis.
Concluding Remarks and Future Perspectives
The profound imprint of COVID-19 on mental health is undeniable. Historical evidence of infectious diseases, particularly respiratory viruses, suggest a risk of psychosis. However, this does not necessarily imply a causative link between the viral pathogen and psychotic disorders. Whilst available evidence supports a biological plausibility for its association, the nature of the psychosis do not align with usual diagnoses. Patients have responded well to low-to-moderate doses of medication, with quicker recovery and a more favourable prognosis. Multiple co-founders must be addressed as they also play a role in the long term impact of a patient’s health.
But the side-effects of treatment suggest that clinicians must consider these and closely monitor patients when treating a novel pathogen. In addition, governments and health providers should provide support for the mental impacts of treatments and procedures in addition to physical effects of a disease in order to provide holistic care. This is in line with NHS principles of patient-focussed care and the WHO’s definition of health which regards mental and social well being as important as the absence of disease.