COVID-19 and The BRAIN: Central and Peripheral Targets
It is well recognised that pneumonia is the key manifestation of coronavirus disease 2019 (COVID-19), even though evidence of the viral effects on other organs are beginning to emerge. Considerable concerns have been raised regarding the impact and challenges on certain vulnerable groups including those with intellectual and mental disability (1) and physical disabilities (e.g stroke patients).
It is interesting to highlight that the brain and nervous systems can also be damaged directly or indirectly by COVID-19 causing varying degree of physical and mental deficits. While many of the earlier studies that emerged from Wuhan city documented impaired consciousness and encephalopathy in those severe COVID-19 cases requiring intensive care (2), and some succumbing to the overwhelming sepsis, a few neurological complications are beginning to attract attention due to their potential impact on long term care when the patients eventually recover from the infection.
Cerebrovascular diseases (CVD) in COVID patients have been reported in the United Kingdom (UK) (2) and USA (3,4) and in 6 out of 214 patients in a Chinese centre (5). Interestingly, most of these involved male subjects and several were younger than 50 years old. The stroke subtypes were mixed (small and large vessel, ischemic and haemorrhagic) and a number had other comorbidities like hypertension and diabetes, and clinical outcome has been varied, from recovery to severe disability and death. There was a striking finding in the UK series where 5 of 6 patients had a positive lupus anticoagulant, suggesting that coagulation activation and thrombin generation due to proinflammatory cytokines may be a predisposing factor (2) and this certainly warrant further investigations and research.
Another interesting neurological complication is the association of COVID-19 with Guillain-Barre syndrome (GBS). In this disorder, the immune system attacks the peripheral nerves and patients usually present with weakness and tingling in the lower extremities. Several COVID patients have been reported to have GBS (6) with variable clinical outcome, depending on the extent of the pneumonia and other complications. Like in CVD, the extensive peripheral nerve involvement again suggests a likelihood that this results from a possible excessive proinflammatory cytokine response, which can be unpredictable in its course and its response to immunotherapy and hence can be challenging to treat and may lead to chronic disabling symptoms for the affected patients. Brain inflammation/infection (encephalitis) from COVID-19 is still very rare though the presence of olfactory and gustatory symptoms has attracted considerable interest because anosmia may be an early warning sign.
While subjects with existing brain disorders are hugely vulnerable to the physical and mental challenges during the COVID-19 pandemic, it is important to recognise that COVID-19 can create not only acute neurological damage but at the same time lead to long term sequelae of chronic disability that will burden both the carers and society. At this moment, it does appear that proinflammatory central and peripheral nervous damage from COVID-19 poses a significant challenge for patients and optimal management will require development of targeted therapies to specifically address these issues.
Xiao Deng, MBBS
Yew-Long Lo, MBBS, FRCP(UK)
Eng-King Tan, MBBS, FRCP (UK)
1. Ken Courtenay. Covid-19: challenges for people with intellectual disability.BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1609.
2. Beyrouti R, Adams ME, Benjamin L, et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry 2020.
3. Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med 2020.
4. Al Saiegh F, Ghosh R, Leibold A, et al. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. J Neurol Neurosurg Psychiatry 2020.
5. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol 2020.
6. Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barre Syndrome Associated with SARS-CoV-2. N Engl J Med 2020.
Competing interests: No competing interests