COVID-19 And The Brain:

Are There Neurocognitive Effects Of The Pandemic?

Prof. Huw Williams - Professor of Clinical Neuropsychology, University of Exeter

Ms. Hope Kent - Research Assistant, University of Exeter

Dr. Bonnie-Kate Dewar - Clinical Neuropsychologist, Neuropsychology Services Ltd. 

Coronavirus (COVID-19) can be a devastating disease, which is having a profound effect on people and societies worldwide. It is a rapidly changing landscape, yet there are increasing reports of neurological and neuropsychiatric complications of COVID-19.

As lives are saved, there are growing questions about possible neuro-cognitive sequelae and the longer term rehabilitation needs of survivors of the acute phase of the illness.

At this stage in the pandemic, many questions remain and our understanding of the disease is rapidly evolving. Nonetheless, we aim to provide here a brief overview of what neurocognitive changes could be expected in some patients after initial recovery from COVID-19, from direct encephalitic effects, indirect effects from inflammatory responses, elevated risk of stroke, hypoxia, and additional psychiatric factors that can affect cognition.

There have been a few case reports of COVID-19 giving rise to Encephalitis 1. A case is reported in a 41-year-old female in Los Angeles, in which it is speculated that induced immunologic response as a result of COVID-19 may cause inflammatory injury and swelling, leading to alterations in consciousness due to increased cerebrospinal fluid pressure. Inflammation such as this can lead to neurological symptoms including seizures, headache, fever, nausea, confusion, and loss of bodily sensations.

A case report of acute necrotising encephalopathy (ANE) has also been reported in a female in her 50s 2. This is a rare immune-mediated complication of viral infection, and has been related to intracranial cytokine storms, which can result in blood-brain-barrier breakdown. Growing evidence suggests that a small group of patients who have survived severe COVID-19 may have a cytokine storm syndrome 3, and possible secondary encephalitis as a result 4. Cognitive impairment is commonly reported following both viral encephalitis and immune-mediated encephalitis 5, and therefore cognitive sequelae of post COVID-19 encephalitis is to be expected.

Another major complication arising from COVID-19 is ischaemic stroke. An early study from Wuhan reported acute cerebrovascular disease, predominantly ischaemic stroke, in patients with more severe forms of COVID-19 6. A London based study reported six consecutive patients assessed in April 2020 with acute ischaemic stroke arising from COVID-19 7. All six patients had large vessel occlusion – i.e. some form of blockage in the blood supply system. Such blockages may be due to embolisms being generated by altered blood clotting in COVID-19. Cognitive impairment is commonly reported after stroke, including problems with memory, executive functioning, language, spatial ability, perception, and information processing depending upon the area of the brain affected.

Another small but significant proportion of individuals with COVID-19 will have acute respiratory failure necessitating treatment with mechanical ventilation in ICU. Hypoxia occurs when oxygen supply to the brain is interrupted, and can lead to confusion, disorientation, delirium and loss of consciousness 8. If prolonged it can lead to cell death (infarction). The experience of ICU, particularly with limited contact from loved ones, can contribute to acute stress, anxiety, delirium, and other psychiatric factors which can also affect cognitive function.

There are few studies of neurocognitive problems after COVID-19 thus far. One provides a guide to inform our expectations. In 58 patients of a study in ICU in France, there were some neurological features such as Transient Ischaemic attacks (mini-strokes) partial epilepsy and mild cognitive impairment. When they followed up at discharge fifteen of 45 patients (33%) showing some signs of dys-executive problems (inattentive, distractible, poor response to command etc.) 9.

We are at a very early stage in social recovery form COVID-19. Given the suspected high numbers of people who may have had the virus, and the severity of the disease in a substantial minority, we do not know what the true legacy may be in the in the long term. There is a need for ongoing research linked to planning and informing responses from frontline health and social care staff and of longer term planning between government agencies, including for employment and business support. Only by appropriate understanding of factors affecting people’s abilities to function in their family - and at work - can survivors be adequately supported to regain fullest functioning.

Given the array of possible sources of brain injury from COVID-19, there can be no ready set of definitive signs and symptoms. However, survivors and their friends and family need to be aware of possible areas to be mindful of as they recover. Questions to ask may be: ‘Do they struggle to pay attention? Plan ahead? Seem muddled when doing a task? Struggle to remember a story? Names of people?’ Of course, the stresses of having hospital care may also cause cognitive effects, so care is needed to not “over-diagnose” too soon and allow recovery to take its course. But in future weeks and months issues may arise and drive the need for assessment and support from GPs and Medical practitioners. Advice from Clinical Neuropsychologists would be beneficial for understanding neurocognitive disorders and taking into account factors such as acute stress and anxiety, to support everyday functioning.

Additional Resources

British Medical Journal
The Neurology and Neuropsychiatry of Covid-19

The British Psychological Society
Coronavirus Resources

References

1 Duong, L., Xu, P., & Liu, A. (2020). Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in Downtown Los Angeles, early April 2020. Brain, Behaviour, and Immunity. doi: 10.1016/j.bbi.2020.04.024 [Epub ahead of print]
2 Poyiadji et al. (2020). COVID-19–associated Acute Haemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology. https://doi.org/10.1148/radiol.2020201187
3 Mehta et al. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. doi: 10.1016/S0140-6736(20)30628-0
4 Ellul, M., et al. (2020). Neurological associations of COVID19. Available at SSRN: https://ssrn.com/abstract=3589350 or http://dx.doi.org/10.2139/ssrn.3589350
5 Hebert et al. (2018). Long-Term Cognitive Outcomes in Patients With Autoimmune Encephalitis. Can J Neurol Sci. DOI: 10.1017/cjn.2018.33
6 Mao, L., Jin, H., & Wang, M. (2020). Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. Jama Neurol. doi:10.1001/jamaneurol.2020.1127
7 Beyrouti, R., et al. (2020). Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery & Psychiatry. doi: 10.1136/jnnp-2020-323586
8 Row et al. (2007). Intermittent hypoxia and cognitive function: implications from chronic animal models. Adv. Exp. Med. Biol., 618, 51-67.
9 Helms, J. et al. (2020). Neurologic Features in Severe SARS-CoV-2 Infection. The New England Journal of Medicine, DOI: 10.1056/NEJMc2008597