key: cord-1021332-0apv0cbh
authors: Vorspan, Florence; Amarsy, Rishma; Etain, Bruno
title: May confusion be a misleading initial clinical presentation of COVID-19 in individuals with mood disorders?
date: 2021-01-04
journal: Psychiatry Res
DOI: 10.1016/j.psychres.2021.113710
sha: 3a119a0bf962df13b869a1bf58bb3e4c72071e89
doc_id: 1021332
cord_uid: 0apv0cbh

nan

Severe Acute Respiratory Syndrome To the Editor, During the first month of the COVID-19 pandemic, as psychiatrists, we have observed some misleading initial clinical presentations of COVID-19 in a small series of cases with already known psychiatric disorders. Between March 10th to April 10th, 2020, for all patients admitted in our university-affiliated hospital in Paris-France for a psychiatric reason for admission, the hygiene department recommended to prescribe PCR and viral RNA test in case of evocative clinical manifestations (cough, dyspnea, fever, headache, anosmia…). However, misleading initial presentations were also likely to occur. Indeed, during this period, two males of 54 and 68 years-old, already being diagnosed with mood disorder (one with unipolar, one with bipolar) were diagnosed with COVID-19 while they were presenting only confusion or isolated catatonic symptoms (obnubilation and echolalia). Those symptoms were considered as a change from their previous clinical psychiatric state but were also different from the clinical presentations of their experienced past mood episodes (no previous episodes with confusion nor catatonic symptoms). Fever and respiratory signs occurred only 24 hours later for one of them and never occurred for the second one.

In order to estimate how frequent such a misleading presentation might be observed, we systematically and retrospectively reviewed the medical files of all the patients who were admitted during the same period and diagnosed as SARS-COV2 PCR positive during their stay in our inpatient facilities. We identified five additional patients with common symptoms of COVID-19. These five patients were diagnosed with mood disorders (3 with bipolar versus 2 with unipolar), with an age range 54-79 years old and exhibited symptoms of COVID-19 such as fever, respiratory symptoms, cough, myalgia, inflammatory symptoms...) in addition to mood disorders, but without confusion or catatonia. Given this clinical experience, we have estimated that 28% of patients with mood disorders and suffering from the COVID-19 infection display confusion or catatonia as an initial clinical sign. This prevalence is exactly the one found by a systematic review published by Rogers et al. 2020 which identified confusion as a common symptom among patients admitted to hospital for COVID-19, SARS or MERS (27,9% of 129 patients) (Rogers, et al., 2020) , a prevalence estimate obtained from two independent studies. This report concerns mostly in patients with severe forms of the disorder, usually in intensive care units, after several weeks of disease evolution. In those cases, a causality attribution of the confusion to the COVID-19 itself is highly difficult, as it could be caused by hypoxia or many other intensive-care related factors. Confusion was rarely isolated there, and often accompanied by either neurological or psychotic symptoms. Among neurological localization signs, authors describe diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes, or persistent executive function impairment after discharge (Helms et al., 2020) . More recently, 10 cases of confusion and persistent delusional psychotic symptoms were described after several weeks of severe COVID-19 respiratory infection in liaison psychiatry patients (Parra et al., 2020) . Interestingly, cerebro-spinal fluid (CSF) PCR when performed revealed no presence of the virus, ruling out a direct neurotropic deleterious effect of the SARS-COV2. Reversely, some patient from those series showed high protein and IgG levels in the CSF, evocative of a secondary deleterious immune response associated with those neurological signs, as previously reported with MERS and SRAS (Helms et al., 2020) . in this context, little is known whether patients with psychiatric disorders would exhibit confusion or misleading clinical presentation more often than patients with no known psychiatric disorders. Furthermore, our case series was characterized by an age range between 54-74 years old. It has been reported that confusion or delirium are frequent in elderly patients, including at early stages of the COVID-19 disease, whether recruited in the emergency department or in specific geriatric series (Kennedy et al. 2020; Vrillon et al., 2020) . In those series, confusion was present in up to 71% of the subjects and was even the only symptom present in up to 16%. In those elderly patients, a confounding effect of hypoxia or cardiac failure observed in severe COVID-19 forms is still possible. Of note, among the patients recruited in geriatric facilities, 48 (63.2%) had already a diagnosed cognitive impairment (Vrillon et al. 2020) , and elderly patients are more vulnerable to confusion or to a worsening of previous cognitive impairment in case of any type of infection (Fard et al., 2020) .

Further case series should investigate whether confusion or other misleading presentations such as catatonia might represent frequently the initial clinical presentation of COVID-19.

Since these patients were not initially presenting with severe respiratory signs, we may retain as plausible the hypothesis of confusion or catatonic symptoms linked with an initial non-specific immune response to the virus, similar to fever or fatigue. This is in line with numerous data showing that patients with psychiatric disorders display low grade inflammation, usually accounted for a shared genetic vulnerability. The link between confusion in the early course of a viral infectious disease and this persistent low-grade inflammation needs to be further investigated. Such a study would require a systematic PCR for all patients admitted in psychiatric ward, along with systematic and structured neurological and psychiatric assessment and CSF or at least plasmatic inflammatory and immune response biomarkers, and possibly PET-scan microglial activation measurements. 

This report follows the French biomedical rules on biomedical research (Loi Jardé) and our hospital policy on the publication of anonymized data collected during routine care. The data repository has a specific authorization from the CNIL (National Commission on Information Technology and Freedom) under the number 2017-013 given on 19 January 2017. Both include the information of the patients and a non-opposition rule.

All authors report that they do not have competing interest with regards to this work.

Funding no specific funding for this work.

FV wrote the first draft of the manuscript. All authors participated in the discussion and approved the final version of the manuscript.

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