BREAKING! COVID-19 News: Italian Researchers Warn That SARS-CoV-2 Infections Can Lead To New-Onset Psychosis! Expect More Loonies Walking Around!
: Italian researchers based on their study findings and also from data collated from two documented clinical cases studies are warning that SARS-CoV-2 infections can also lead to the new onset of psychosis.
Psychosis is a multifactorial condition that typically involves delusions, hallucinations, and disorganized thought, speech or behavior.
Typical as with many other mental disorders, psychosis can be triggered by several different causes, including psychiatric, neurodevelopmental, neurologic, and medical conditions.
It has already been known and covered in various past COVID-19 News
coverages that SARS-CoV-2 infections can affect the function of the central nervous system (CNS) and damage the CNS via both direct invasion and immune activation. The virus can enter the brain through several routes. It can migrate through the axons of many nerves, including the olfactory, trigeminal, and vagus nerves. SARS-CoV-2 can also access the CNS by infecting endothelial cells of cerebral vessels or by invading perivascular spaces of the glymphatic system.
At the CNS level, the ACE2 expressing neural cells include dopaminergic and serotonergic nuclei, glutamatergic neurons, substantia nigra and the lateral ventricles.
All these brain regions are neurochemically and structurally involved in schizophrenia (SCZ) and while damage to these CNS sites may not necessarily reflect causation; their relative vulnerability to SARS-CoV-2 infection may play a role in shaping future psychopathology.
Localization matters in this respect, in as much penetration of the virus in circumventricular organs may confer vulnerability to many neuropsychiatric outcomes.
Furthermore, the SARS-CoV-2 receptor: ACE2 exhibits significant genetic co-expression with dopamine decarboxylase, an enzyme involved in dopamine and serotonin synthetic pathways.
Importantly, it has been suggested that SARS-CoV-2-induced downregulation of ACE2 expression may be paralleled by alterations of both dopamine and serotonin synthesis, possibly leading to psychiatric sequelae.
It has also been noted that COVID-19-related CNS dysfunction may also result from systemic inflammation, often known as systemic inflammatory response syndrome or “cytokine storm”.
The massive increase in circulating pro-inflammatory factors may deeply affect the blood–brain barrier (BBB) integrity, allowing inflammatory cells and molecules to access the CNS.
Neuroinflammation perturbs brain homeostasis, alters neural networks, and eventually induces neuronal deaths. Both the infection itself and hypoxia stimulate cytoki
ne release, which can increase BBB permeability. Cerebral hypoxia may activate key inflammatory transcription factors, resulting in an overproduction of pro-inflammatory messengers as well as in an excessive glial reactivity which further contributes to the loss of synapses and neurons.
Furthermore, circulating pro-inflammatory factors may enhance hypothalamic–pituitary–adrenal (HPA) axis activity, which contributes to sustaining and promoting neuroinflammation due to glucocorticoid increase.
Though SARS-CoV-2 is rarely found in the cerebrospinal fluid, viral-induced immune reactions and autoimmunity (during or after the acute infection) may provide another route by which SARS-CoV-2 can impact CNS function.
Systemic inflammation has long been recognized as a potential immune-related trigger in the pathogenesis of neuropsychiatric manifestations associated with viral infections.
According to a vulnerability–stress–inflammation hypothesis of psychotic illness, stress during both pre- and postnatal neurodevelopment may prime the individual for an abnormal response to future stressors, typically during adolescence or early adulthood.
It has been established that biological stressors, such as viral infections and immune activation, may affect the HPA axis, whose dysregulation contributes to some abnormalities observed in schizophrenia (SCZ), including increased baseline cortisol and reduced hippocampal volume, as well as disturbances in dopamine and glutamate transmission.
Furthermore, microglia may release pro-inflammatory factors in response to stress or infection and, similarly to the HPA axis, can be primed by neurodevelopmental stressors.
Importantly, overactivation of microglial cells may be involved in the pathophysiology of schizophrenia (SCZ), leading to abnormal synaptic pruning and to altered neurotransmitter metabolism secondary to augmented cytokine release.
Interestingly, individuals with COVID-19 and associated psychotic symptoms may show an increased level of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, CRP, ferritin, LDH, and D-Dimer.
Likewise, an upregulation of pro-inflammatory factors seems to characterize drug-naïve patients in their first episode of psychosis.
Furthermore, there is evidence for a longitudinal association between increased C-reactive protein (CRP) serum levels in adolescence and diagnosis of psychotic spectrum disorders in adulthood.
Aside from all of the above, autoimmunity may also be implicated in the pathogenesis of psychotic illness.
Accordingly, there is evidence for both shared genetic risk factors between several immune diseases and schizophrenia (SCZ), and for an increased risk of developing psychotic spectrum disorders in individuals with autoimmune illnesses and severe infections that required admission to hospital.
In the context of SARS-CoV-2 infection, several cases of patients with COVID-19 and associated CNS autoimmune demyelinating disease have been reported.
Interestingly, several demyelinating disorders are related to the presence of psychotic symptoms and, according to evidence, reduced CNS white matter integrity secondary to demyelination may play a role in the pathophysiology of schizophrenia (SCZ).
The Italian study team comprised of researchers form the following institutions:
-Department of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, L.go Agostino Gemelli-Italy
-Department of Neuroscience, Section of Psychiatry, Università Cattolica del Sacro Cuore-Italy
-Department of Neurosciences, Mental Health, and Sensory Organs (NESMOS), Sapienza University of Rome, Sant’Andrea Hospital, Via di Grottarossa-Italy
-Department of Mental Health, Local Health Authority ROMA 2-Italy
The study team also presented two cases studies involving two patients admitted to the outpatient psychiatric service of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy) between 1 July 2020 and 1 July 2021 with new-onset psychosis and delusions, and who had reported a history of recent SARS-CoV-2 infection.
A female aged 48 years was diagnosed with bilateral pneumonia and mild respiratory insufficiency related to SARS-CoV-2 infection. She had been admitted to the hospital in mid-April 2020.
Detailed blood works showed an inflammatory state, including elevated serum C-reactive protein and leukocytosis.
The female patient was treated with high-flow oxygen as well as with oral lopinavir–ritonavir, hydroxychloroquine, and ibuprofen. After three weeks of hospitalization, once the patient’s medical conditions had improved considerably and the SARS-CoV-2 nasal/oropharyngeal swab was negative, she was discharged.
However, in June 2020, she presented to the emergency department (ED) accompanied by two family members, complaining somatic delusions concerning widespread pains and internal organ failure, initial insomnia, and psychomotor retardation. She tested negative on nasal/oropharyngeal swab.
It was noted that st the time the patient came to ED, she presented with no psychiatric or family history and did not take any medication. Laboratory tests were normal, and no psychotropic substances were present in her urine drug screen. She was admitted to an internal medicine ward for further investigation.
After admission, the patient became mute, unresponsive to external stimuli, and showed postural rigidity. Clinical electroencephalography was normal. Similarly, magnetic resonance imaging revealed no morphological or structural alterations within brain tissues and the whole ventricular system. The liaison psychiatrist suspected patient’s withdrawal was a catatonic symptom and administered a lorazepam challenge of 2 mg IV with good response. Lorazepam was administered at the dose of 2 mg PO every 8 h leading to a complete recovery from catatonic symptoms within seven days.
At a subsequent psychiatric interview, the patient appeared alert and oriented as to place and time. Her mood was neutral. She reported a history of restlessness, low appetite, and olfactory hallucinations as well as delusional beliefs of being “rotten inside” shortly after her first discharge from the hospital for COVID-19. She was prescribed aripiprazole 15 mg PO daily in addition to lorazepam. Three weeks after admission, she was calm with no evidence of psychotic symptoms.
She was discharged home with a diagnosis of acute and transient psychotic disorder according to the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 and admitted to the outpatient psychiatric clinic for regular follow-up appointments. Lorazepam was gradually discontinued, whereas aripiprazole was reduced to 10 mg PO daily and eventually discontinued after 6 months without a return of delusional symptoms. She is currently well.
This time a female aged 42 years was brought to the outpatient psychiatric consulting room by her sister in July 2020. Divorced, she lived with her 18-year-old daughter, who was affected by multiple sclerosis. The patient had neither known chronic psychiatric conditions, including substance use disorders, nor was taking any long-term medications. Similarly, her family history was free from psychiatric disorders.
It was noted that in May 2020, she tested positive on the SARS-CoV-2 nasal/oropharyngeal swab, reporting high fever, fatigue, sore throat, and dry cough. Wishing to protect her daughter from the infection, the patient decided to move to another house in Rome. She stayed isolated for 13 days, after which she gradually recovered, though she continued suffering from anosmia and ageusia. She did not require any specific treatment for her COVID-19.
At the time of the psychiatric examination, the patient reported the onset of tactile and visual hallucinations, in the form of bugs crawling on or underneath her skin, two weeks after the beginning of the infection. She washed her hands several times a day with chemical detergents and was extremely worried that the bugs may infest her daughter too, so she decided not to come back home after she recovered from COVID-19.
The patient also visited a dermatologist who diagnosed a severe form of contact dermatitis and referred her to a psychiatric consultation. The patient was administered risperidone 2 mg PO daily, which was increased to 3 mg a week later. The patient showed a significant improvement in her delusional beliefs as well as an increase in her insight and judgement/reasoning abilities within one week after the onset of the treatment. Risperidone was gradually reduced to 1 mg PO during the follow-up and the patient did not show any relapse. She is about to discontinue her risperidone completely.
The study findings and the two case studies were published a review in the peer reviewed Journal of Personalized Medicine.
With billions of people now already exposed to the SARS-Cov-2 virus and many more getting constantly reinfected, neuropsychiatric issues including psychosis and various other mental disorders are going to become another common occurrence that society and the healthcare infrastructure will have to deal.
In summary, we can expect to have more ‘fruitcakes’ walking around in society!
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