key: cord-1009224-ix6igyfn
authors: Scheiner, Nathan S.; Smith, Ashley K.; Wohlleber, Margaret; Malone, Challyn; Schwartz, Ann C.
title: COVID-19 and Catatonia: A Case Series and Systematic Review of Existing Literature
date: 2021-04-20
journal: J Acad Consult Liaison Psychiatry
DOI: 10.1016/j.jaclp.2021.04.003
sha: f2f388a7333bc5a45b67b1eb953e5e0933e1ffcc
doc_id: 1009224
cord_uid: ix6igyfn

BACKGROUND: Current observational literature on the mental health impact of the COVID-19 pandemic has focused on anxiety, depression, and sleep-disturbance among the public, healthcare workers, and COVID-19 patients. Case reports suggest catatonia and psychosis may be presenting symptoms of COVID-19 disease with a mechanism postulated to involve central nervous system changes in response to inflammation. There is a lack of robust evidence examining catatonia in this context. We sought to systematically review available case data and contextualize our findings. CASE PRESENTATIONS: We present three cases of patients with catatonia seen at a large metropolitan tertiary care hospital in which their catatonia was likely attributable to SARS-CoV-2 infection. Ms. A is a female in her 50s with no psychiatric history who presented with self-inflicted stab wounds following her COVID-19 diagnosis. Ms. B is a female in her 50s with a history of schizophrenia, but no history of catatonia, who presented with akinetic catatonia, SARS-CoV-2 infection, and Clostridium difficile infection, without respiratory manifestations of COVID-19. Ms. C is a female in her 20s with a history of bipolar disorder (type 1) without catatonic features who presented with akinetic catatonia without the physical symptoms of SARS-CoV-2 infection. DISCUSSION: We present a brief review of six case reports detailing co-occurring catatonia and SARS-CoV-2 infection and one case report of catatonia attributed to the psychological stress of the COVID-19 pandemic in a patient without SARS-CoV-2 infection. We note one additional case of co-occurring catatonia and SARS-CoV-2 infection for which details are not available. COVID-19-associated catatonia may develop secondary to psychological and physical factors. Cases often report anxiety preceding catatonic symptoms. Developing evidence also suggests SARS-CoV-2 may act directly on the central nervous system or via a systemic inflammatory response. One of our cases featured significant anxiety preceding symptoms, and two had co-occurring elevated serum inflammatory markers. We suggest that clinicians should keep a high index of suspicion for both clinically significant anxiety disorders and catatonia.

Current observational literature on the mental health impact of the COVID-19 pandemic has focused on anxiety, depression, and sleep-disturbance among the public, healthcare workers, and COVID-19 patients. Case reports suggest catatonia and psychosis may be presenting symptoms of COVID-19 disease with a mechanism postulated to involve central nervous system changes in response to inflammation. There is a lack of robust evidence examining catatonia in this context.

We sought to systematically review available case data and contextualize our findings.

We present three cases of patients with catatonia seen at a large metropolitan tertiary care hospital in which their catatonia was likely attributable to SARS-CoV-2 infection. Ms. A is a female in her 50s with no psychiatric history who presented with self-inflicted stab wounds following her COVID-19 diagnosis. Ms. B is a female in her 50s with a history of schizophrenia, but no history of catatonia, who presented with akinetic catatonia, SARS-CoV-2 infection, and Clostridium difficile infection, without respiratory manifestations of COVID-19. Ms. C is a female in her 20s with a history of bipolar disorder (type 1) without catatonic features who presented with akinetic catatonia without the physical symptoms of SARS-CoV-2 infection.

We present a brief review of six case reports detailing co-occurring catatonia and SARS-CoV-2 infection and one case report of catatonia attributed to the psychological stress of the COVID-19 pandemic in a patient without SARS-CoV-2 infection. We note one additional case of cooccurring catatonia and SARS-CoV-2 infection for which details are not available. COVID-19associated catatonia may develop secondary to psychological and physical factors. Cases often J o u r n a l P r e -p r o o f

The World Health Organization declared the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to be a pandemic on March 11, 2020. 1 As of February 25, 2021, there have been approximately 112 million cases and 2.5 million confirmed deaths attributable to COVID-19 disease. 2 The physical, biochemical, and imaging characteristics of SARS-CoV-2

infection are well described. 3, 4 Recent data implicate SARS-CoV-2 involvement in a wide range of central nervous system (CNS) manifestations of the disease. 5 SARS-CoV-2 is postulated to enter the CNS via translocation from the cribriform plate to the orbitofrontal cortex 6 or via hematologic spread. 7 The potential mechanisms for the neurological and neuropsychiatric effects of the virus are many and include direct viral encephalitis, as well as less direct effect of the infection, including inflammation, hypoxia, hypercoagulability, postinfectious auto-immunity, or effects of immunomodulatory treatments. 8 Psychiatric symptoms have also been reported, though data are limited. A recent review and meta-analysis by Krishnamoorthy, et al. 9 found that of 50 studies examining mental health outcomes, only four were focused on outcomes among patients infected with SARS-CoV-2. All studies were cross-sectional, and the majority measured self-reported symptoms, typically using online surveys. Existing data describe depression, anxiety, "psychological distress," posttraumatic symptoms, "poor sleep quality," and insomnia among healthcare workers, the general population, and COVID-19 patients. 9 Catatonia is a potentially fatal psychomotor condition characterized by neurovegetative and motor tone changes, as well as psychological echoing. 10 Duplicate records were excluded automatically and manually using EndNote. Titles were reviewed for relevance and irrelevant titles or non-English articles were excluded. We then assessed full-text articles; they were excluded if they were irrelevant, not a clinical report, a systematic review or meta-analysis not discussing catatonia, or case reports that discussed psychotic or manic illness in the context of COVID-19 but without a relevant finding of catatonic features (see Figure 1 ). Eight records are presented in the discussion as a review of current literature. Ms. A later reported a 10-day history of anxiety, low appetite, and depressed mood about her recent COVID-19 diagnosis. She could not recall her catatonic episode or whether she experienced suicidal ideation, but did believe that her catatonic symptoms preceded her self-J o u r n a l P r e -p r o o f inflicted injury. She was oriented without alterations in consciousness and denied auditory or visual hallucinations, paranoia, or delusions. Her thought process was well-organized, and she did not appear to be responding to internal stimuli.

Ms. A was treated with 1mg lorazepam by mouth (PO) every 8 hours for catatonia and 6mg melatonin PO nightly to restore the sleep/wake cycle. While inpatient, she denied symptoms of coronavirus infection including fever, myalgia, fatigue, respiratory or gastrointestinal symptoms, which remained stable over the course of her admission. Following several days of observation, lorazepam was changed and tapered to clonazepam 0.5mg PO daily, and mirtazapine was initiated for depression and appetite stimulation and titrated to 30mg nightly.

She discharged to home on HD#8 with outpatient psychiatric follow-up where benzodiazepines were discontinued at three weeks, and she had no recurrence of symptoms at five weeks.

Ms. B is a female in her fifties with a history of schizophrenia and chronic kidney disease stage 3 who was brought to the ED from a local jail twice for "refusal to eat." On assessment by psychiatry, she reported her refusal to eat was volitional to secure hospital admission. She did not appear psychotic, suicidal, or homicidal on either visit and discharged back to jail. Ms. B presented a third time for "refusal to leave" jail property after release. She was electively mute and only said "let me lay down" in a whispered voice. Her behavior was felt to be volitional, and

she was again discharged. The following day, bystanders reported she had been lying on the sidewalk since her discharge, raising suspicion for acute medical illness.

Ms. B was returned to the ED by paramedics and received intramuscular haloperidol, Since discharge, she has had multiple presentations to the ED for unrelated medical complaints.

Ms. C is a female in her twenties with a history of bipolar disorder (type 1) who presented to the ED after exhibiting bizarre behavior. She was discharged from a four-day inpatient psychiatric hospitalization one day prior to the current presentation. During that admission, she was stabilized for an acute manic episode without psychotic symptoms with extended-release oral lithium 900mg nightly and returned near her baseline mental status. She tested negative for SARS-CoV-2 at that time and had no prior history of catatonic features. Per patient's mother, following discharge, she showed paranoia towards family and refused to accept food or water for fear that it had been tampered with. Ms. C went to another family member's house at her own request where she ate, but did not sleep, and called her mother early the next morning requesting to return to the hospital. On the car ride to the hospital, she was noted to be staring and mute. Ms. C continued to exhibit verbigeration, mutism, and had poor memory of recent events. She said that she felt "foggy" but was unable to provide further details. She denied fever, chills, malaise, myalgias, sore throat, cough, nausea, vomiting, or diarrhea.

She was started on 1mg oral lorazepam TID. Lithium was titrated to 1500mg PO nightly to target a serum concentration of 1.0 mEq/L. Following transfer to the psychiatric inpatient unit, she displayed paranoia, pseudocyesis, and appeared to be responding to internal stimuli, and aripiprazole 10mg daily was initiated. Ms. C had resolution of catatonic symptoms (BFCRS = 0) on HD#20 and was discharged on HD#26 without psychotic symptoms. She was subsequently lost to follow-up.

We identified eight records reporting catatonia in the context of the SARS-CoV-2 pandemic (see Table 1 ). Seven were detailed case reports, six of which described patients with SARS-CoV-2 infection and one which described catatonic symptoms attributed to the psychological stress of the pandemic. Caan et al. 12 first reported the case of a 43-year-old male without past psychiatric or medical history who presented to the ED several times following his COVID-19 diagnosis with complaints of anxiety and insomnia that eventually progressed to akinetic catatonia. This was followed by a case report of an 80-year-old male presenting with moderately severe COVID-19 pneumonia who later developed akinetic catatonia. 13 Importantly, the authors demonstrated a rise in pro-inflammatory markers typically seen in COVID-19 disease (lymphocyte count, CRP, D-dimer, Ferritin, lactate dehydrogenase, and procalcitonin) concurrent with the onset of catatonia, that suggested an immune-mediated or inflammatory mechanism.

Catatonia is also reported in patients with other medically complex COVID-19 disease.

Zandifar and Badrfram discuss a 61-year-old male with a history of schizophrenia who was admitted to psychiatry and became symptomatic with COVID-19 disease and hyponatremia on HD#2, that progressed to seizures and akinetic catatonia. 14 Amouri et al. 15 reported a 70-year-old female with critical hypoxic respiratory failure due to COVID-19 pneumonia and delirium who subsequently developed akinetic catatonia, noting the increased risk of catatonia due to delirium as well as SARS-CoV-2. A striking case by Deocleciano de Araujo et al. 16 similarly details a 50-

year-old male with mild intellectual disability who was admitted with akinetic catatonia in the setting of a friend's recent suicide and was initially found to have asymptomatic SARS-CoV-2 infection with elevated pro-inflammatory markers. This case was complicated by aspiration pneumonia and acute hypoxic respiratory failure which required ICU admission and electroconvulsive therapy.

Authors have also reported akinetic catatonia in a non-infected Italian patient with no prior psychiatric history, presumably secondary to the psychological stress of lockdown, 17 and a 23-year-old previously healthy Peruvian female who had otherwise asymptomatic SARS-CoV-2 infection that presented with psychosis and akinetic catatonic features in the setting of elevated serum inflammatory markers. 18 The eighth report comes from compiled data of 157 patients submitted to United

Kingdom researchers via an online data-reporting scheme for providers early in the pandemic. 19 While these authors note that a concurrent case of catatonia and SARS-CoV-2 infection was reported, details are not available.

It is surprising there are few reported cases of catatonia in SARS-CoV-2 infection. Up to 20% of catatonia is caused by medical illness, 20 its non-psychiatric correlates are welldescribed, 21 and catatonia has been associated with other viral pandemics in the 19 th and 20 th centuries. Encephalitis lethargica, characterized by profound lethargy and abnormal movements, was used to describe catatonic symptoms that followed infection with influenza in the pandemic of 1918. 22 Given the lack of robust observational data on COVID-19 associated catatonia, there is significant debate about its pathogenesis. Existing literature, and our cases, suggest both inflammation and anxiety may play a role in the development of catatonia among COVID-19

patients.

While we did not exhaustively review cases of psychosis without catatonic features, This question clearly requires larger observational studies.

Finally, publication bias is likely, such that only remarkable cases have been reported.

We note that several cases did not use a standardized symptom scale, such as the BFCRS.

Standardized reporting among authors may help identify additional subtle cases and add richness to the phenomenology of catatonia in COVID-19 disease.

Our cases and the literature highlight two issues. The first is that SARS-CoV-2 may have a role in causing catatonia via inflammation or CNS action. This is particularly salient for inpatient providers caring for COVID-19 patients who have entered the inflammatory phase of illness. Given the morbidity and mortality associated with catatonia, inpatient and consulting psychiatrists should keep a high index of suspicion for catatonia when consulted for abnormal behavior or altered mental status in COVID-19 patients.

The second key point is the importance of screening for and prompt treatment of anxiety in patients with less severe COVID-19 disease. Ms. A's course demonstrates that prompt recognition and treatment of acute depression and anxiety may have prevented self-harm.

However, limited access to outpatient psychiatric services during the COVID-19 pandemic remains an ongoing issue. 31 We emphasize the importance of the psychological stress of the SARS-CoV-2 pandemic. Pandemics in general, 32 and COVID-19 33 Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Informed consent: Ms. A gave verbal informed consent to publish her case. Ms. B could not be reached to discuss informed consent due to lack of contact information on her chart. Ms. C was unable to participate in an informed consent discussion and verbal consent was given by her surrogate (mother).

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