COVID-19 and the Brain – Pathogenesis and Neuropsychiatric Manifestations of COVID-19

Posted on:May 17, 2020
Last Updated: December 7, 2023
Time to read: 33–40 minutes

The COVID-19 pandemic is caused by the novel coronavirus (CoV), SARS-CoV-2, that predominantly affects the respiratory system. However, there is increasing evidence that SARS-CoV-2 can be neuroinvasive, resulting in neuropsychiatric complications. [Troyer et al. 2020]

This article is one of the articles on SARS-CoV-2 Pandemic and mental health.

  1. Psychological impact of quarantine
  2. Mental health challenges for healthcare workers during the COVID-19 pandemic – Impact and management strategies

Pandemics are large scale outbreaks of infectious disease that can overwhelm the psychological and emotional tolerance of both healthcare workers and the public.

Psychological stress associated with the fear of illness and the uncertainty of the future can result in direct and vicarious traumatisation. [Li et al. 2020]

Biologically,  the host immune response to the virus itself may also impact the central nervous system (CNS) by precipitating virus-induced neuropsychiatric sequelae.

Historically, past influenza pandemics have been associated with a post-infection increase in anxiety, insomnia, fatigue, depression, suicidality, and delirium [Honigsbaum 2013]. Also, there is some debate as to whether the Spanish flu pandemic of 1918 was causally associated with encephalitis lethargica as a neurological consequence. [Hoffman L & Vilensky J., 2017]

There are several viruses with neurotropic potential; influenza virus, human metapneumovirus, members of the Enterovirus/rhinovirus genus, echoviruses, coxsackieviruses, respiratory syncytial virus, Hendra and Nipah viruses.

Taxonomically similar coronaviruses such as SARS-COV and MERS-COV have previously been associated with neuropsychiatric sequelae.

For example, in the case of SARS-COV, autopsy studies showed cerebral oedema and meningeal vasodilation. Microscopically, infiltration of monocytes and lymphocytes in the vessel wall, ischaemic neuron changes, demyelination and detection of SARS COV viral particles and genome sequences in the brain were detected. [Wu Y et al., 2020]

The MERS-CoV outbreak in 2012, also precipitated neuropsychiatric symptoms as a result of an immunological reaction. [Tsai et al. 2004], [Kim et al. 2017]

A systematic review and meta-analysis [Rogers J et al., 2020] of the neuropsychiatric manifestations of SARS and MERS CoV revealed that during the acute illness, common symptoms included confusion (27.9%), depressed mood (32.6%), anxiety (35.7%), impaired memory (34.1%) and insomnia 41.9%.

In the post-illness stage, depressed mood (10.5%), insomnia (12.1%), anxiety (12.3%), irritability (12.8%), memory impairment 18.9%, fatigue 19.3%, traumatic memories (30.4%) and sleep disorder (100%) were frequently reported.

The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2%, depression 14·9% and anxiety disorders was 14·8%.

Using our knowledge of what manifested beyond the acute stage of infection can thereby inform our understanding of the current pandemic.

In this article, we cover the current evidence for the pathophysiology of SARS-CoV-2 CNS involvement with clinical manifestations and treatment options. We focus on the role of the psychiatrist in the neuropsychiatric landscape of COVID-19.


First case of 2019 novel coronavirus disease with Encephalitis.
Xiang, P., Xu, X. M., Gao, L. L., Wang, H. Z., Xiong, H. F., & Li, R. H. (2020). First case of 2019 novel coronavirus disease with Encephalitis. ChinaXiv, 202003, 00015.
Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study.

Li, Y., Wang, M., Zhou, Y., Chang, J., Xian, Y., Mao, L., … & Li, M. (2020). Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study.