key: cord-0837286-pdog45w9
authors: Huarcaya-Victoria, Jeff; Meneses-Saco, Alejandra; Luna-Cuadros, María Alejandra
title: Psychotic symptoms in COVID-19 infection: A case series from Lima, Peru
date: 2020-08-09
journal: Psychiatry Res
DOI: 10.1016/j.psychres.2020.113378
sha: ce2a8d866d8f96d53b7b6e8854065f0bf5e9ea67
doc_id: 837286
cord_uid: pdog45w9

nan

 In the reported cases, a direct causal relationship between COVID-19 and the appearance of psychotic symptoms is not established.

 The psychotic outbreak could be explained as a multifactorial process.

Mechanisms such neuroinvasion or systemic inflammatory processes have limited evidence.

 Future longitudinal studies with adequate control of confounding variables are required to determine any causality between SARS-CoV-2 and psychotic symptoms.

Jeff Huarcaya-Victoria a, b, *, Alejandra Meneses-Saco a , María Alejandra Luna-Cuadros This case involves a 23-year-old female patient from Lima, a student, with no psychiatric history. Three days before admission, her father informed her that he had tested positive for COVID-19. This news caused the patient anxiety and fear. Two days before admission, the patient presented with fever (38.4ºC). One day before admission, she slept only 2 hours, showed mystical religious delusions and strange behaviors, spoke incoherently, and stated that she heard voices calling her and telling that her "mother was going to die of COVID-19." The next day, she presented with psychomotor agitation, the reason she was admitted to a health center. There she was given intravenous midazolam with little effect and was then referred to our hospital.

Upon giving her a mental evaluation, we found the patient to be awake, albeit with decreased attention and imperative, pejorative, and auditory hallucinations, along with delusions of damage and reference; formal thought disorder; anxiety; irritability;

catatonic symptoms (stereotyped movements, catalepsy, verbigeration); bizarre behavior; and insomnia. No comorbid symptomatology such as depression, fatigue, or post-traumatic stress disorder symptoms were found. The Duration of Untreated Psychosis (DUP) was one day.

In the blood count we found the following: Leukocytes: 8,060; hemoglobin: 11.9; platelets: 329,000; segmented: 70%; lymphocytes: 25%; and Neutrophil-Lymphocyte Ratio (NLR): 2.8. The qualitative detection of IgM/IgG antibodies against COVID-19 was reactive.

This patient was diagnosed with an acute psychotic disorder, in addition to COVID-19.

She received 40 mg ziprasidone upon admission. After nine days of hospitalization, the patient was discharged with remission of psychotic symptoms. Her medication at discharge was 15 mg/day olanzapine.

This case involved a 38-year-old female patient from Lima, a street vendor, with a history of depressive episodes without diagnosis or psychiatric treatment. Family members reported that 14 days before admission the patient presented with insomnia.

Seven days before admission, the patient began "talking too much," showing no signs of fatigue. Three days before admission, the patient remained awake all night. She said that "she saw a light that was God who entered her room," spending the whole night praying. The next day the patient began to speak incoherently, and her mystical religious delusions became more intense. On the day of admission, more bizarre behaviors occurred (kneeling on the floor to pray, reading the Bible aloud, speaking with a foreign accent). Therefore, she was brought to the emergency department of our hospital.

Upon giving her a mental evaluation, we found the patient awake and easily distracted, with auditory hallucinations, mystical delusions, euphoric mood, bizarre behavior, psychomotor restlessness, and insomnia. No comorbid symptomatology such as depression, fatigue, or post-traumatic stress disorder symptoms were found. The DUP was 3 days.

In the blood count we found the following: Leukocytes: 10,850; hemoglobin: 12.9; platelets: 329,000; segmented: 74%; lymphocytes: 20%; NLR: 3.7; and C Reactive Protein (CRP): 6 mg/L. The qualitative detection of IgM/IgG antibodies against COVID-19 was reactive.

The patient was diagnosed with an acute psychotic disorder, in addition to COVID-19.

She received 20 mg ziprasidone upon admission. After 10 days of hospitalization, the patient was discharged with total remission of psychotic symptoms and partial remission of affective symptoms. Her medication at discharge was 20 mg/day olanzapine, 1,000 mg/day valproic acid; and 1 mg/day clonazepam.

This case involved a 47-year-old female patient from Lima, a housewife, with no history of diagnosis or psychiatric treatment. Four months before admission, her mother died, after which she began to develop feelings of sadness and guilt. Three weeks before admission, the patient presented with an acute psychotic syndrome characterized by auditory hallucinations ("I heard the voice of a woman telling me to kill myself"), delusions of harm, and suicide attempts, for which she was taken to the emergency department of our hospital.

Upon giving her a mental evaluation, we found her to be awake, with auditory hallucinations, delusions of damage, formal thought disorder, suicidal thoughts, depressed and anxious mood, irritability, fatigue, and insomnia. The DUP was 27 days.

The blood count revealed the following: Leukocytes: 5,130; hemoglobin: 13.9; platelets 384,000; segmented: 73.4%, lymphocytes: 15.4%, NLR: 4.76. CRP: 1.5 mg / L. The qualitative detection of IgM / IgG antibodies against COVID-19 was reactive.

This patient was diagnosed with an acute psychotic disorder, in addition to COVID-19.

She received 15 mg haloperidol on admission. After 10 days of hospitalization, the patient was discharged with total remission of her psychotic symptoms and suicidal ideation. Her medication at discharge was 300 mg/day quetiapine, 50 mg/day sertraline, and 500 mg/day valproic acid.

The neuropsychiatric complications of COVID-19 are still not entirely clear. Past pandemics have evidenced an epidemiological association between viral infections and neuropsychiatric symptoms. However, causality and etiopathogenic mechanisms have not been clarified (Kępińska et al., 2020) . Currently, various theories try to explain the mechanism by which psychotic symptoms may appear in COVID-19: direct invasion of the central nervous system (CNS), systemic immune response, or adverse reaction to drugs against COVID-19, among other possible causes.

It has been postulated that SARS-CoV-2 can enter the CNS by hematogenous and/or retrograde neuronal spread. Hematogenous spread could occur via two mechanisms: the passage of infected white blood cells that cross the blood-brain barrier or through a direct infection of the endothelial microvascular cells that express the angiotensin-converting enzyme 2 (ACE2) (Raony et al., 2020) . Neuronal retrograde spread can occur via two pathways, the olfactory nerves or the enteric nerves (Raony et al., 2020) .

When SARS-CoV-2 infects the airways, it can cause an acute respiratory syndrome with the consequent release of pro-inflammatory cytokines, such as interleukins (IL) 1β and IL-6, causing the "cytokine storm." These cytokines have been found to be more abundant in chronic psychotic disorders such as schizophrenia (Raony et al., 2020) .

However, in some contexts it is not possible to study these cytokines, so we can indirectly assess their increase through an elevation of various inflammatory parameters. A quick, easy way to assess the state of systemic inflammation is by the NLR, which can be calculated from a complete blood count. Elevations of the NLR have been associated with an increase in cytokines such as IL-6 and IL-8 (Karageorgiou et al., 2019) . In a study carried out in patients experiencing a first episode of psychosis, a mean NLR of 2.7 ± 1.9 has been documented (Moody & Miller, 2018) . In the three cases reported here, we have found an elevation of the NLR (2.8, 3.7, and 4.76), which may suggest a generalized inflammatory state. However, we must remember that these descriptions are only anecdotal associations, so we cannot state any type of causality.

In the reported cases, a direct causal relationship between SARS-CoV-2 and the appearance of psychotic symptoms is not established. In most of these cases, the psychotic outbreak could be explained as a result of different pathogenic mechanisms, from neuroinvasion, systemic inflammatory processes, and psychosocial response (stress of isolation and change of life during the pandemic), among others. Future longitudinal studies with adequate control of confounding variables are required to determine any causality between SARS-CoV-2 and psychotic symptoms.

Neutrophil-to-lymphocyte ratio in schizophrenia: A systematic review and meta-analysis

Schizophrenia and influenza at the centenary of the 1918-1919 Spanish influenza pandemic: Mechanisms of psychosis risk. Front Psychiatry

Total and differential white blood cell counts and hemodynamic parameters in first-episode psychosis

Psycho-neuroendocrine-immune interactions in COVID-19: Potential impacts on mental health

Reactive psychoses in the context of the COVID-19 pandemic: Clinical perspectives from a case series