key: cord-1013178-othg9lb2 authors: Ravindran, Navna Panchami; Halder, Ankit; Harshe, Devavrat; Harshe, Sneha; Harshe, Gurudas title: A qualitative analysis of literature reporting and linking psychosis to COVID-19 infection. Findings from a postgraduate journal club. date: 2022-04-06 journal: Asian J Psychiatr DOI: 10.1016/j.ajp.2022.103099 sha: 2d6e30c9968cb58831eb635866e2854770ba5442 doc_id: 1013178 cord_uid: othg9lb2 Acute exacerbations of psychosis have been reported with COVID-19 infection and medications used for its treatment. Terms “psychosis”, “psychotic”, “COVID-19” and “coronavirus” were searched on “PubMed” and “GOOGLE SCHOLAR”, yielding 84 articles. 14 case reports were selected based on pre-defined criteria and analyzed. Among selected articles,10 attributed psychosis to COVID-19 infection. In 3 articles, psychosis was diagnosed despite concurrent delirium. In 8 and 3 articles respectively, a clear temporal demarcation of psychosis and COVID-19 infection and steroid use was not described. Psychosis can occur secondary to GMC, or exposure to medication. Due process should be followed to ascertain the same. INTRODUCTION: Neurotropic coronavirus infection is associated with numerous neurological and neuropsychiatric manifestations. Such presentations before, during and after the infection have been reported. Among these presentations, acute exacerbations of psychosis have been reportedly linked with COVID-19 infection and medications used for its treatment. METHODOLOGY: Search engines “PubMed” AND “GOOGLE SCHOLAR” were searched using specific search terms during June 2021. Out of 84 articles that came up, we selected 14 articles based on pre-determined inclusion and exclusion criteria. Selected articles were analysed and discussed in the departmental journal club. RESULTS: In 10 articles, diagnosis of psychosis was attributed to COVID-19 infection. In 3 of those articles, despite reporting concurrent delirium like presentation, diagnosis was still reported as psychosis. In 8 articles, the temporal correlation between onset of psychosis, onset of COVID-19 was not clearly demarcated. In 3 articles, clear demarcation between psychosis associated with steroid use and with a general medical condition (COVID-19) was not clearly presented. Only 2 articles did mention using a structured diagnostic system. In patients (3/17) with prior history of psychiatric illness, diagnosis was reported as relapse of psychosis (2/17), without specifying the criteria used for diagnosing a relapse. CONCLUSION: Acute exacerbation of psychosis can occur secondary to a general medical condition (GMC), or after exposure to a medication. However, due process should be followed to ascertain that the psychosis is indeed secondary to a GMC, or a medication, and not a de-novo presentation, or delirium. Coronaviruses have been linked to neuropsychiatric manifestations during and after the infection (Lahiri et al. 2020 , Ellul et al. 2020 , Niazkar et al. 2020 , Rehman U et al. 2021 , Rentero et al. 2021 , Hyland P et al. 2020 , Kozloff et al. 2020 , Bodnar et al. 2021 . Immunological mechanisms, COVID-19 treatment, cognitive impairment, poor psychosocial functioning, pre-existing psychiatric or neurological disorder and adverse geopolitical situations due to the pandemic were hypothesized to be causally associated with presentations of psychosis (Bodnar et al. 2021 ). Here we present discussions, deliberations and observations at a departmental journal club, focussing on scientific literature reporting psychosis in patients diagnosed with COVID-19. All the articles relevant to the study, as per inclusion and exclusion criteria, were taken up and analysed. Concerns with regards to reporting psychosis in COVID-19 pandemic were highlighted. We used the guidelines and criteria mentioned in DSM-5 (American Psychiatric Association et al. 2013) for psychotic disorders due to other medical conditions, and judged ( 2. Symptoms that are atypical in nature and course. 3 . A possible link with a medication/substance of abuse. In most articles the title hinted at a link between psychosis and COVID 19 (Hansen et al.2020 , Parker et al. 2021 , Alba et al. 2021 ,Noone et al. 2020 ,Kozato et al. 2021 ,Smith et al. 2020 ,Lim et al. 2020 ,Lanier et al. 2020 ,Majadas et al. 2020 ,Correea-Placio et al. 2020 . Two articles suggested a possible role of quarantine in onset of psychosis (Sanchez et al. 2020 , Baral et al. 2021 . Psychosis was reported in some articles as the presenting feature of COVID-19, (Parker et al. 2021 , Noone et al. 2020 , Lanier et al. 2020 , Correea et al. 2020 , Ferrando et al. 2020 , Saje et al. 2021 , whereas, some reported psychosis as a neuropsychiatric manifestation following symptoms of COVID-19 (Hansen et al.2020 , Alba et al. 2021 , Noone et al. 2020 , Kozato et al. 2021 , Smith et al. 2020 , Lim et al. 2020 , Majadas et al. 2020 , Baral et al. 2020 . J o u r n a l P r e -p r o o f To diagnose psychosis due to a general medical condition, a temporal association between the two has to be established. We found articles that mentioned psychosis as the presenting feature of COVID-19 (Parker et al. 2021 , Noone et al. 2020 (b), Lanier et al. 2020 , Correa-Placio et al. 2020 , Ferrando et al, Saje et al. 2021 . Eight (Hansen et al. 2020 , Alba et al. 2021 , Noone et al. 2020 , Kozato et al. 2021 , Smith et al. 2020 , Lim et al. 2020 , Majadas et al. 2020 , Baral et al. 2021 ) have reported COVID-19 like illness prior to onset of psychotic symptoms. Eight have not shared the details regarding duration passed between a positive RT PCR swab and onset of psychosis (Sanchez et al. 2020 , Parker et al. 2021 , Kozato et al. 2021 , Lannier et al. 2020 , Majadas et al. 2020 , Correa-et al. 2020 , Ferrando et al. 2020 , Saje et al. 2021 ). The stressors in workplace/life and infections, metabolic imbalances, chronic debilitating diseases act as psychological stressors and hence precipitate psychosis (Phillips et al. 2007 , Corcoran et al. 2003 . Loss of livelihood, separation from loved ones during mandated quarantine can Atypical age at onset, is one of the guidelines for considering psychosis due to another medical condition (American Psychiatric Association et al. 2013) . In this study, mean age at onset of psychotic episodes was above 40 years, which is within the second of the bimodal peaks of schizophrenia onset (Sham et al. 1994) . Psychotic disorders show a marked prevalence between 15-17 years (American Psychiatric Association et al. 2013 , Kessler et al. 2007 , World Health Organization et al. 2004 , higher age at onset can be atypical for onset of psychosis. Hence, while reporting psychosis due to another medical condition, background treatment modalities and their side effect profiles should be considered. Smith et al. 2021 , Lim et al. 2021 ). Among inflammatory markers, CRP was most often raised (Majdas et al. 2020 , Ferando et al. 2020 , Baral et al. 2021 ) followed by BUN (Parker et al. 2021) . Inflammatory markers such as IL-1 beta, IL-6 and growth factors like GF beta can be raised during acute exacerbations in schizophrenia (Kirkpatrick et al. 2013) . Stress due to infections or metabolic instability can also raise inflammatory markers and cytokines (Marsland et al. 2017 ). Further, remission of psychosis is accompanied by reduction in level of inflammatory markers (Haring et al 2015) . Fluvoxamine, an antidepressant gained a brief spotlight during the pandemic and it was hypothesized that fluvoxamine, due to its activation of S1R-IRE1 pathway, reduced the inflammatory markers, thus alleviating symptoms of COVID-19 (Lenze et al. 2020) . It may therefore be prudent to consider that, inflammatory markers, though elevated in acute infections, can also be elevated in psychiatric disorders themselves. used in treatment and their interactions may predispose patients to delirium or more often sub-syndromal delirium, which can be overlooked or missed (Sepulveda et al. 2017) . Thus, there is a possibility of delirium masking or masquerading as psychosis in COVID-19 infection. One article reported case of an adult male with pre-existing schizoaffective disorder, on a maintenance dose of clozapine, who presented with psychosis during mandated quarantine after a febrile illness (Sanchez et al. 2020) . It was reported as a relapse of psychosis. However, schizoaffective disorder require coexistence of either depressive or manic episode with core symptoms of schizophrenia for at least a month (American Psychiatric Association et al. 2013), which was not fulfilled in the clinical presentation described. In the same report, details about whether clozapine was discontinued, or down-titrated during the febrile illness were not mentioned. This history is relevant, since high grade fever (101F) in a patient taking clozapine warrants investigations to rule out agranulocytosis, or Neuroleptic Malignant Syndrome (NMS) (Karagianis et al. 1999) . These can mimic symptoms of COVID-19 and the following psychotic episode could have been due to, reduction/discontinuation of clozapine, or physical/psychological burden of febrile illness. In some articles, chronic and severe metabolic, infectious and degenerative disorders were reported during the clinical work-up, such as hepatic encephalopathy, Lewy Body Dementia and Toxoplasmosis (Parker et al. 2021) . All these can present with behavioral disturbances or delirium caused by the disease process, yet, the diagnosis was reported as psychosis due to COVID-19. There is handful literature that explained these issues previously (Dinakaran et al. 2020 , Megahed et al. 2020 , Ashrafi et al. 2020 , Banerjee et al. 2020 .This article highlights important concerns about reporting a clinical phenomenon occurring concurrently with another comorbid illness. This is perhaps the first such effort in this domain. It is vital for scientific writers not to engage in the age old fallacy; Event X happened after This manuscript also has some limitations. Due to heterogeneity in design, we limited our research only to case reports and series and excluded randomized trials and observational studies. Since our search was conducted in the month of June 2021, articles published on later dates might have employed a more exploratory and indirect approach in reporting this clinical phenomenon. Patients with COVID-19 can present with psychosis or other psychiatric symptoms at any stage of the infection. However, it is important to differentiate the presentations as, 1) de novo presentation of psychosis, 2) psychosis due to psychological or physiological burden of COVID-19, 3) psychosis due to various geopolitical changes associated with the pandemic, 4) psychosis as a consequence of various medications used in treatment of COVID-19 and 5) delirium. All ethical guidelines were followed thoroughly during this research and respective authors for each article were cited appropriately. Neurotropic coronavirus infection is associated with numerous neurological and neuropsychiatric manifestations. Such presentations before, during and after the infection have been reported. Among these presentations, acute exacerbations of psychosis have been reportedly linked with COVID-19 infection and medications used for its treatment. Search engines "PubMed" AND "GOOGLE SCHOLAR" were searched using specific search terms during June 2021. Out of 84 articles that came up, we selected 14 articles based on pre-determined inclusion and exclusion criteria. Selected articles were analysed and discussed in the departmental journal club. In 10 articles, diagnosis of psychosis was attributed to COVID-19 infection. In 3 of those articles, despite reporting concurrent delirium like presentation, diagnosis was still reported as psychosis. In 8 articles, the temporal correlation between onset of psychosis, onset of COVID-19 was not clearly demarcated. In 3 articles, clear demarcation between psychosis associated with steroid use and with a general medical condition (COVID-19) was not clearly presented. Only 2 articles did mention using a structured diagnostic system. In patients (3/17) with prior history of psychiatric illness, diagnosis was reported as relapse of psychosis (2/17), without specifying the criteria used for diagnosing a relapse. Acute exacerbation of psychosis can occur secondary to a general medical condition (GMC), or after exposure to a medication. However, due process should be followed to ascertain that the psychosis is indeed secondary to a GMC, or a medication, and not a de-novo presentation, or delirium. 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