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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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“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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“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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Citations
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Items 101–199 of 199
Delirium in Critically Ill Cancer Patients With COVID-19
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“Further investigation is warranted to discern whether delirium in COVID-19 signifies a primary encephalopathy heralding viral invasion of the CNS or a secondary complication stemming from systemic inflammation [33].”
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“In a case series fromMassachusetts General Hospital, the authors reported that in addition to the typical features of delirium, patients displayed significant agitation, increased tone or rigidity, abulia, alogia, and evidence of significant systemic inflammatory response [5].”
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Garcia-Rada, M. F., & Litman, R. E. (2022) · PubMed Central · Cited by 3
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“…scientific works report the development of metabolic dysregulation ( Aguila-Gordo et al., 2021; Portincasa et al., 2020), and excessive immune system response (Huang et al., 2020), leading in some cases to a cytokine-mediated secondary encephalopathy (Beach et al., 2020; Stracciari et al., 2021).”
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“Furthermore, a series of cases from Wuhan showed that at least 20% of patients who eventually died from COVID-19 had had signs of encephalopathy [3,7].”
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“Contributing factors include severe respiratory failure, prolonged Invasive Mechanical Ventilation (IMV) with deep sedation, isolation, and the systemic inflammatory response associated with COVID-19 [3, 10–12].”
Psychotic Symptoms After SARS-CoV-2 Infection
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“Despite this, another case included in the review showed how its use in combination with Trazodone in a patient with severe systemic diseases could have an insufficient effect on symptom resolution [41].”
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COVID-19 and Hospital-Acquired Delirium
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“If parkinsonism or akinetic mutism is suspected, dopaminergic therapies may be of benefit; if catatonia, benzodiazepines; and in all three instances, amantadine, a glutamate N-methyl-D-aspartate receptor antagonist that secondarily modulates dopamine, may be effective, as was the case here.(22)”
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“Unfortunately, data on CRP level was not available in our study population.”
BackgroundInfluentialICU Delirium in the Era of the COVID-19 Pandemic
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Neurological Presentations of COVID-19
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Análise dos mecanismos fisiopatológicos no surgimento da encefalite aguda em pacientes com COVID-19
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Delirium in Patients with Covid-19
Madhusudhan, S., Shreekara, Chandrashekar, H., Sharma, P., Amit, A., Jeevan, & Anjana, R. M. (2022) · Acta Scientific Neurology · doi:10.31080/asne.2022.05.0476
Lima, B. S., Cardoso, B. E. M., Teixeira, L. R., de Bastos, A. P. S., da Paz, F. L. L., Ferreira, J. G. D. O. R., Mendonça, G. D. S., Pacheco, R. C., de Araújo, L. S. F., Magalhães, H. G. D. A., et al. (2022) · Research Society and Development · doi:10.33448/rsd-v11i5.27745
Post-acute Delirium of COVID-19 Infection
Chi, D.-C., Chu, C.-P., Yang, T. W., & Chang, H. (2022) · Taiwanese Journal of Psychiatry · doi:10.4103/tpsy.tpsy_6_22
Delirium in COVID-19: An Atypical Case Managed With Quetiapine
Silva, M. L., Gul, O., Aravally, V. P., Khalid, M., & Williams, T. (2022) · Cureus · doi:10.7759/cureus.25776
“Emerging evidence has revealed delirium as an atypical clinical presentation of COVID-19 infection in the absence of upper respiratory symptoms [2-4].”
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Covid 19 Pandemisi ve Deliryum
Biricik, E., & Güneş, Y. (2022) · Arşiv Kaynak Tarama Dergisi · doi:10.17827/aktd.1055896
Psychological Impacts of the COVID-19 Pandemic
Powell, S. K., Saali, A., Serafini, R. A., O’Shea, C. P., Frere, J. J., & Katz, C. L. (2022) · Springer eBooks · doi:10.1007/978-3-031-08045-6_10 · Cited by 2
Ferrer, L., Díaz, J. C., Cardenas, Y., Vergara, P., Portilla, M. R., Fernández, M. G., VALENCIA, B. A. G., Vargas, M., Flórez, H. J. M., & Castell, C. R. D. (2022) · Medicina Crítica · doi:10.35366/106512 · Cited by 1
Emotional and Behavioral Symptoms
Byrne, R., Elsner, G., & Beattie, A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-76174-1.00031-6
Neuropsychiatric side of the COVID-19
Mayorova, M. A., Churilov, L. P., Петрова, Н. Н., & Shoenfeld, Y. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18566-3.00007-4
Sizemore, G., Lucke-Wold, B. P., & Small, C. N. (2022) · PubMed
Delirium in a Relatively Young Person due to COVID-19 Infection
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“In our case, the possible mechanism behind delirium could be a direct central nervous system (CNS) invasion of COVID-19 or an inflammatory reaction due to systemic infection, as other environmental-related conditions are minimal due to the shorter hospital stay [20].”
BackgroundThe psychiatric effects of COVID-19 in the elderly
Sarangi, A., & Kumar, S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-15256-6.00015-5
Navigating the Neurological Aftermath of COVID-19: An In-Depth ExplorationPreprint
Butt, M. M., Nagpal, S., Phillips, E., Shah, S. Q., Dogar, Z. G., Loh, H., Mishra, S., Vijayan, R., Jeyakumar, R., Makkar, S. S., et al. (2023) · medRxiv · doi:10.1101/2023.09.10.23295343
COVID-19 Current Management and Strategies for Future Outlook
Shaik, N. K., Poojitha, N., Chandana, K. B. S., Vidyavathi, M., & Venkata, S. D. R. (2023) · International Journal of Pharmaceutical Investigation · doi:10.5530/ijpi.13.4.091
Gangguan Serebellar pada Pasien Berusia 55 Tahun dengan Multiple System Atrophy
Maulidia, A. A. (2023) · Majalah Kedokteran Neurosains Perhimpunan Dokter Spesialis Saraf Indonesia · doi:10.52386/neurona.v39i4.388
ALTERAÇÕES NEUROLÓGICAS CONSEQUENTES DA COVID-19
Pereira, S. S., & Almeida, A. N. D. (2023) · Revista Foco · doi:10.54751/revistafoco.v16n10-206
Neurological Implications in Elderly COVID-19 Patients Hospitalized in Mexico
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Psychiatric Drugs. Toxicology: Respiratory Failure—Noninvasive Mechanical Ventilation
Soubani, O., Bains, A., & Soubani, A. O. (2023) · Noninvasive ventilation. The essentials · doi:10.1007/978-3-031-44626-9_20
Psychiatric Pharmacology and Acute Respiratory Failure
Soubani, O., Bains, A., & Soubani, A. O. (2023) · Noninvasive ventilation. The essentials · doi:10.1007/978-3-031-44626-9_18
Nörolojik Acillerde Tanı ve Tedavi Prensipleri
Eren, F., DEMİR, A., Güneri, Ş. Ç., Aktürk, T., Aktürk, U. D., Küçük, A., Şahin, O., Tekinalp, N., Saçmacı, H., Sönmez, M. T., et al. (2022) · Akademisyen Kitabevi eBooks · doi:10.37609/akya.996
Investigation of Neuropsychological Dysfunction Among Recovered Nurses: The COVID-19
Salemi, M. H., & Alipour, A. (2024) · Cureus · doi:10.7759/cureus.58929
“Researchers acknowledge COVID-19 as a disease that affects multiple organs and presents with a diverse range of symptoms [4].”
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Viral Targeting of Mitochondria May Alter Cognition and Enhance Viral Transmission
Stefano, G. B. (2024) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202406043
Mind-Body Medicine – A journey beyond the helplessness barrier
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Mind-Body Medicine: A Funder´s Perspective
Lüdtke, R. (2024) · THE MIND - Bulletin on Mind-Body Medicine Research · doi:10.61936/themind/202406044
Acute neurocognitive disorder as a presenting manifestation of COVID-19
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Postmortem neuropathology in COVID-19
Duarte‐Neto, A. N., Junior, J. C. G., Paes, V. R., Saldiva, P. H. N., & Dolhnikoff, M. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19170-1.00006-1
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“While neurological manifestations of SARS-CoV-2 are predominantly associated with severe infections [18], a subset of patients can exhibit them following mild or asymptomatic cases [13–15].”
Pu, J., Chen, W., 蒋航成, & Yang, H. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1844317
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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