The DOI matches its Crossref record; 40 of the 48 references it cites were found in a registry or an index.
Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement
Open accessAbstract
Introduction Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options.Cases We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).Discussion The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium.Conclusions Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.
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“Particularly affected were people with dementia, who presented often with agitation (16, 18–20) and altered consciousness (15, 18).”
From The impact of COVID-19 infection and enforced prolonged social isolation on neuropsychiatric symptoms in older adults with and without dementia: A review (2020) · cites this paper as [16]
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“At hospitalisation, all patients presented with agitation and 7 out of 8 with delirium.”
From The impact of COVID-19 infection and enforced prolonged social isolation on neuropsychiatric symptoms in older adults with and without dementia: A review (2020) · cites this paper as [16]
In the citing paper
“In all cases, the neuropsychiatric manifestations of COVID-19 were clinician-reported.”
From The impact of COVID-19 infection and enforced prolonged social isolation on neuropsychiatric symptoms in older adults with and without dementia: A review (2020) · cites this paper as [16]
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Cites
Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China
Mao, L., Jin, H., Wang, M., Hu, Y., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1127 · Cited by 7,166 · cited 1×
“turbed consciousness, and neuropsychiatric symptoms seem to be associated with more severe disease [1].”
Endothelial cell infection and endotheliitis in COVID-19
Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., Mehra, M. R., Schuepbach, R. A., Ruschitzka, F., & Moch, H. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30937-5 · Cited by 6,358 · cited 1×
“ACE2 receptors are also expressed by endothelial cells, and endotheliitis has also been implicated in the pathology of the virus as a result of both direct and indirect mechanisms [29].”
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., O’Meara, M. J., Rezelj, V. V., Guo, J. Z., Swaney, D. L., et al. (2020) · Nature · doi:10.1038/s41586-020-2286-9 · Cited by 4,405 · cited 1×
“While haloperidol carries theoretical risk of EPS, it is worth noting that the IV form is rarely associated with EPS, add haloperidol is now on the list of medications being studied as a treatment for SARS-CoV-2 because of its effects on sigma receptors [33].”
Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study
Chen, T., Wu, D., Chen, H., Yan, W., Yang, D., Chen, G., Ma, K., Xu, D., Yu, H., Wang, H., et al. (2020) · BMJ · doi:10.1136/bmj.m1091 · Cited by 3,903 · cited 2×
“Prior case series have determined that 20–65% of patients with SARS-CoV-2 display features consistent with delirium, and our cases illustrate that mental status changes can occur as the presenting feature [2,6].”
Neurologic features in severe SARS-CoV-2 infection
Helms, J., Kremer, S., Merdji, H., Clere-Jehl, R., Schenck, M., Kummerlen, C., Collange, O., Boulay, C., Fafi-Kremer, S., Ohana, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2008597 · Cited by 2,674 · cited 6×
“thermore, while a test for detecting virus in the CSF has been described in other countries [2,7], such a test is not yet available in the United States.”
InfluentialLechien, J. R., Chiesa-Estomba, C. M., De Siati, D. R., Horoi, M., Le Bon, S. D., Rodriguez, A., Dequanter, D., Blecic, S., El Afia, F., Distinguin, L., et al. (2020) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-020-05965-1 · Cited by 2,668 · cited 2×
“It is also known that up to 88% of patients develop anosmia or ageusia, thought to be secondary to invasion of the olfactory bulb by the virus, suggesting brain involvement [3].”
Li, Y., Bai, W., & Hashikawa, T. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25728 · Cited by 2,266 · cited 1×
“It is known that some coronaviruses, like SARS-CoV, appear capable of invading the brain via a synapse-connected chain extending from receptors in the lung to the medullary cardiorespiratory center [13].”
Baig, A. M., Khaleeq, A., Ali, U., & Syeda, H. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00122 · Cited by 2,207 · cited 1×
“The brain has been reported to express ACE2 receptors that have been detected in both neurons and glial cells [27], which makes them vulnerable to SARS-CoV-2 invasion [28].”
Nervous system involvement after infection with COVID-19 and other coronaviruses
Wu, Y., Xu, X., Chen, Z., Duan, J., Hashimoto, K., Yang, L., Liu, C., & Yang, C. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.03.031 · Cited by 2,046 · cited 1×
“While some authors suggest these as elements of a workup for all patients [31], this may not be practical due to tenuous clinical status, cost, exposure of staff, and resource availability (i.”
A first case of meningitis/encephalitis associated with SARS-Coronavirus-2
Moriguchi, T., Harii, N., Goto, J., Harada, D., Sugawara, H., Takamino, J., Ueno, M., Sakata, H., Kondo, K., Myose, N., et al. (2020) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2020.03.062 · Cited by 2,024 · cited 4×
“While the preceding accompaniments of the virus may be interpreted as indirect CNS effects, a report from China describes the first case of viral encephalitis with COVID-19, confirmed by cerebrospinal fluid (CSF) analysis [7].”
Influential
Cited by
Sorted by citations
Guillain Barre syndrome associated with COVID-19 infection: A case report
Sedaghat, Z., & Karimi, N. (2020) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2020.04.062 · Cited by 600
Harapan, B. N., & Yoo, H. J. (2021) · Journal of Neurology · doi:10.1007/s00415-021-10406-y · Cited by 360
“Independent of the etiology of delirium, hospitals should consider adding mental status changes to the list of testing criteria since delirium may be the only presenting symptom [48].”
BackgroundDelirium in Older Patients With COVID-19 Presenting to the Emergency Department
Kennedy, M., Helfand, B., Gou, R. Y., Gartaganis, S. L., Webb, M. A., Moccia, J. M., Bruursema, S., Dokic, B., McCulloch, B., Ring, H., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.29540 · Cited by 288
“00) Rehabilitation 111 (14) 41 (18) 70 (12) 1.”
BackgroundInfluentialImpact of COVID-19 in the Mental Health in Elderly: Psychological and Biological Updates
Grolli, R. E., Mingoti, M. E. D., Bertollo, A. G., Luzardo, A. R., Quevedo, J., Réus, G. Z., & Ignácio, Z. M. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02249-x · Cited by 286
Frequency of Neurologic Manifestations in COVID-19
Misra, S., Kolappa, K., Prasad, M., Radhakrishnan, D. M., Thakur, K. T., Solomon, T., Michael, B. D., Winkler, A. S., Beghi, E., Guekht, A. B., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000012930 · Cited by 255
Metadata
- Authors
- Beach, S. R., Praschan, N. C., Hogan, C., Dotson, S., Merideth, F., Kontos, N., Fricchione, G. L., & Smith, F. A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Beach, Scott R.
- ORCID
- Venue
- General Hospital Psychiatry
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 65
- Pages
- 47-53
- ISSN
- 0163-8343 (ISSN-L)
- PMC
- PMC7242189
- OpenAlex
- W3026414252
- Cited by
- 199
- References
- 48
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 14 · 2023: 22 · 2022: 47 · 2021: 70 · 2020: 40
- FWCI
- 19.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- General Hospital Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Social Sciences › Psychology › Clinical Psychology › COVID-19 and Mental Health
- Keywords
- COVID-19 pandemic, SARS-CoV-2, delirium, central nervous system involvement, neuropsychiatric symptoms, cognitive decline, older adults, rigidity, alogia, abulia, inflammatory markers, systemic inflammatory response, encephalopathy, psychiatric consultation
- MeSH terms
- COVID-19, Aged, Aged, 80 and over, Brain Diseases, Delirium, Female, Humans, Male, Pneumonia, Viral, Coronavirus Infections, Pandemics, Cognitive Dysfunction
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