Neurovirulent Potential of COVID-19 in Humans

By Adriana Ramos Calvo 

In December 2019, a novel virus, which was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by the ICTV (International Committee on Taxonomy of Viruses) made its first appearance in Wuhan, China (Bchetnia, Girard, Duchaine and Laprise, 2020). The disease this virus causes (coronavirus disease 2019 or COVID-19) was declared a pandemic by Dr. Tedros Adhanom Ghebreyesus, World Health Organization’s Director-General on March 11th, 2020, since the virus had already affected a rapidly increasing number of countries (WHO announces COVID-19 outbreak a pandemic, 2020). Some of the symptoms associated with this disease are acute respiratory distress syndrome (ARDS) and severe pneumonia, among others. As the number of the individuals affected by COVID-19 is quickly increasing, a great effort is being put towards investigating if this disease has neurological associations as well (Calcagno et al., 2020).  

SARS-CoV-2 is the third known zoonotic β-coronavirus after MERS-CoV and SARS-CoV, which cause the Middle East Respiratory Syndrome (MERS) and SARS, respectively. Discoveries from former studies of these human coronaviruses (CoV) suggest that they can disseminate to other regions, including the central nervous system (CNS), instead of remaining confined to the respiratory system – in other words, they have the potential of being neurotropic and neurovirulent. These studies suggest the mechanisms used by SARS-CoV-2 to enter the CNS may include hematogenous dissemination and the neuronal retrograde route, through trans-synaptic transfer via peripheral nerve terminals (Calcagno et al., 2020).

Considering the similarities between SARS-CoV-2 and SARS-CoV and the neurotropic properties of the latter, it is reasonable to believe that neuroinvasion can be a consequence of COVID-19. A recent study showed that up to one-third of COVID-19 sufferers showed signs of at least one non-specific or specific neurological symptom. The former included fatigue, myalgia and headache, among others, while the latter were seizures, comas and cerebrovascular disease, which were reported in critical cases of the disease (Calcagno et al., 2020). 

A recent study carried out by neurologists at the University College London (UCL) examined 43 British COVID-19 sufferers and diagnosed acute demyelinating encephalomyelitis (ADEM) in nine of them, which causes a brief but widespread inflammation in the brain and spinal cord that damages the myelin sheaths covering the nerve fibers. Twelve patients suffered of inflammation of the central nervous system, ten from a transient encephalopathy with psychosis, eight from strokes, and eight had problems related to the peripheral nervous system; this was mostly the Guillain-Barré syndrome, which attacks the nerves and can cause paralysis. Regardless of the similarities between SARS-CoV-2 and the other two zoonotic β-coronaviruses, according to Dr. Michael Zandi, the lead author of the UCL study, no other known virus attacks the brain in the same way SARS-CoV-2 does, in the sense that severe brain damage can be observed in patients with mild symptoms (www.dw.com, 2020). 

Due to the difficulty of working with individuals who are severely affected by COVID-19 because of their medical instability, other studies have been carried out post-mortem. One of them has been published in The New England Journal of Medicine, in which a team from Brigham and Women’s Hospital, Boston used neuropathological techniques, combined with reverse transcriptase quantitative PCR (RT-qPCR) and immunohistochemistry to examine brain tissue from 18 deceased patients. The two last techniques showed minimal evidence of SARS-CoV-2 infection, while neuropathological analysis showed changes consistent with hypoxic injury (Wood, 2020).

What will happen next? Associating neurological diseases with SARS-CoV-2 can be challenging, especially if the respiratory infection was asymptomatic or mild or the symptoms appeared weeks after the primary COVID-19 illness. Despite the fact that the proportion of patients that will show neurological symptoms remains small, these individuals may suffer severe sequelae. Furthermore, considering the number of cases registered, even if they are a small proportion, the overall number of neurological patients can be high. The proportion of central nervous system complications ranged from 0.04% for SARS to 0.2% for MERS, while peripheral nervous system complications ranged from 0.05% for SARS to 0.16% for MERS. The number of patients that will suffer neurological complications of COVID-19 can then be extrapolated: given 4.8 million total cases, 1805-9671 of them would suffer CNS complications, while 2407-7737 of them would experience PNS complications. As a consequence, policy makers and health-care planners have to prepare for the economic and social costs and health burden associated with these diseases (Ellul et al., 2020). Moreover, physicians around the world need to remain vigilant, since British neurologists fear that some of the sequelae of COVID-19 may imply subtle brain damage that will only become evident in the coming years (www.dw.com, 2020). 

To sum up, more investigation is necessary to confirm if all of these neurological complications were caused by a disproportionate inflammation response or if they were caused by direct viral infection of the brain tissue, since this would determine the type of treatment needed. If an anti-inflammatory treatment was used when an antiviral one was needed or vice versa, this could only worsen the consequences.

References:

(www.dw.com), D., 2020. COVID-19: Severe Brain Damage Possible Even With Mild Symptoms | DW | 09.07.2020. [online] DW.COM. Available at: <https://www.dw.com/en/coronavirus-brain-damage/a-54111054&gt; [Accessed 19 September 2020].

Bchetnia, M., Girard, C., Duchaine, C. and Laprise, C., 2020. The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A review of the current global status. Journal of Infection and Public Health,.

Calcagno, N., Colombo, E., Maranzano, A., Pasquini, J., Keller Sarmiento, I., Trogu, F. and Silani, V., 2020. Rising evidence for neurological involvement in COVID-19 pandemic. Neurological Sciences, 41(6), pp.1339-1341.

Ellul, M., Benjamin, L., Singh, B., Lant, S., Michael, B., Easton, A., Kneen, R., Defres, S., Sejvar, J. and Solomon, T., 2020. Neurological associations of COVID-19. The Lancet Neurology, 19(9), pp.767-783.

Wood, H., 2020. New insights into the neurological effects of COVID-19. Nature Reviews Neurology, 16(8), pp.403-403.

World Health Organization. 2020. WHO Announces COVID-19 Outbreak A Pandemic. [online] Available at: <https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic#:~:text=COVID%2D19%20can%20be,growing%20number%20of%20countries.&gt; [Accessed 19 September 2020].

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