Viral Infections And Their Neurological Complications

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Overview

It is increasingly recognised that infectious diseases can target the nervous system, leading to serious neurological complications. These neurological symptoms significantly increase the morbidity and mortality associated with infectious diseases. Therefore, understanding the causes of these complications is crucial for developing effective treatments and preventive strategies.

An introduction to infectious diseases 

An infectious disease is an illness caused by a pathogen that is transmitted from an infected person, animal, or object to a susceptible host.1 Infectious diseases pose a substantial global health burden, impacting public health systems and economies on a global level, with vulnerable populations often disproportionately affected.2

This article will focus on three emerging infectious diseases: Zika virus, Coronavirus, and HIV. Emerging infectious diseases are those that are newly identified in a population or have existed but are quickly increasing in incidence or geographic range.3

Zika 

Zika virus (ZIKZ), a mosquito-borne flavivirus, was first established in the 1940s in a monkey in Uganda and later in humans in Nigeria. Originally thought to be a mild disease, only a handful of infections were reported before 2007 and most were located in Africa. However, Zika came to global attention when outbreaks occurred in Micronesia in 2007,  French Polynesia in 2013, Brazil in 2015 and the USA in 2016.4 

Fever, rash, muscle pain and conjunctivitis are the symptoms most commonly associated with this infection.5 Interestingly, until 2015, ZIKV was not thought to cause neurological symptoms in humans.6 However, recent research has shown that acute ZIKV infection during pregnancy may result in infection of fetal brain tissue, causing microcephaly and other debilitating neurological malformations in fetuses and newborns.7

Coronavirus 

In December 2019, a novel coronavirus, SARS-CoV-2, emerged in Wuhan, China, causing a series of acute atypical respiratory illnesses later named COVID-19.8 The virus spread rapidly, reaching pandemic levels in 2020 and resulted in significant economic disruption, personal hardship, and the deaths of an estimated 3 million people worldwide.9,10

While COVID-19 primarily affects the respiratory system, approximately 35% of patients have reported experiencing acute and subacute neurological manifestations.11 Common neurological symptoms include stroke, seizures, neuropathy, and myopathy. Additionally, long COVID can lead to persistent neurological symptoms such as cognitive impairment (brain fog), headaches,11 and verbal fluency deficits.12

HIV 

The retrovirus HIV-1 is transmitted through body fluids and secretions. With more than 75 million people worldwide infected, HIV remains a major cause of morbidity and mortality, particularly in sub-Saharan Africa and Latin America.13 Untreated HIV replication results in progressive CD4+ T cell loss, immunological abnormalities and eventually AIDS-defining opportunistic infections and cancers.14

HIV-1 infection is associated with a spectrum of neurocognitive complications, ranging from mild deficits to dementia, collectively termed HIV-associated neurocognitive disorders (HAND).15 Despite advancements in antiretroviral therapy, HAND continues to be a significant global issue.16

Entering the central nervous system

The central nervous system (CNS) consists of the brain and the spinal cord. Dysfunction of cells in the CNS is a key characteristic of neurological disorders.17 

Interestingly, the CNS is commonly described as having immune privilege.18 This status is largely attributed to the blood-brain barrier (BBB), which supports normal neuronal function by sustaining brain homeostasis and restricting the ingress of pathogens and toxins.19 Despite this protective barrier, the CNS remains a target for multiple neuroinvasive viral agents. Some of these agents, such as the ZIKZ, can cross the intact BBB without compromising it, while others, like COVID-19, can alter the permeability of the BBB or hide within immune defence cells (i.e. HIV-1) to gain entry.20,21,17 

Once access is gained, neurological complications may arise from multiple different pathways.

The connection between neurological complications and infectious aetiology 

The way that viral infections induce neurological complications is often complex and multi-faceted. Damage to cells and neural pathways may be caused directly by infection of the CNS or indirectly, through the host response to the infection.22 

Direct pathway 

Some viral infections can directly infect neurons and other cells in the CNS. 

This is exemplified by ZIKZ. ZIKZ has been shown to infect both mature and immature neurons and alter their cellular metabolism, inducing neurological malignancies.23,24 It is well accepted in the literature that the primary targets of ZIKZ are neural progenitor cells (NPCs), which are cells that develop into glial and neuronal CNS cell types. Infected neurons differentiated from NPCs presented an impairment of neurogenesis (neuron development) and synaptogenesis (synapse formation) processes which can impair brain growth.25 ZIKZ has been shown to alter the cell cycle of other CNS cells, namely neuroepithelial cells and neural cortical stem cells, by inducing apoptosis (cell death).6 

COVID-19 has also been linked to direct infection of neuronal and other CNS cells. Conversely, it is thought that HIV is not capable of attacking neurons directly. Instead, it establishes infection in other cell types, such as microglial cells and harms neurons through indirect pathways.26

Indirect pathway 

In addition to the direct infection of CNS cells, infectious diseases can cause neurological complications through multiple indirect pathways.22 These indirect pathways include:

Brain hypoxia 

The CNS relies on a consistent supply of oxygenated blood to function properly. Brain hypoxia occurs when oxygen levels in the brain are insufficient, which can lead to several pathological changes. Oxygen is crucial for cellular function, and its deficiency can result in: 

  • Oedema (Swelling): Hypoxia can cause cerebral oedema, increasing intracranial pressure and further compromising oxygen delivery.
  • Disturbed Cell Metabolism: Without adequate oxygen, cells switch to less efficient anaerobic metabolism, leading to lactic acid buildup and cellular dysfunction.
  • Neurological Manifestations: Hypoxia can cause a range of neurological issues, including confusion, seizures, loss of consciousness, and in severe cases, permanent brain damage or death.

COVID-19 which is associated with severe respiratory issues such as pneumonia, can cause respiratory insufficiency and systemic hypoxia. This reduced oxygen availability is one of the ways in which the virus is thought to cause neurological damage.26 

Neuroinflammation 

Many viral infections trigger an inflammatory response within the CNS. Microglia, the predominant immune cells in the brain, respond to neuroinflammation by secreting key inflammatory mediators. However, sustained viral infection can result in chronic activation of microglial cells, which can lead to the release of pro-inflammatory molecules. Continuous exposure of neurons to inflammatory mediators can cause neuronal dysfunction, destruction of neural circuitry and cell degeneration.27 This is thought to be one of the main pathways through which HIV-1 enacts neuronal damage and causes subsequent neurological manifestations.28 

So why is this becoming such a big problem? 

Viral infections are increasingly becoming a significant global health concern due to a confluence of factors, including ageing populations, climate change, and globalisation.

Largely as a result of socioeconomic development and healthcare innovations, the global population has aged rapidly over the last few decades. This trend poses particular problems as ageing increases the vulnerability of the CNS to viral infections. Changes in the BBB associated with ageing can heighten the neurotrophic potential of viral infections in older adults.22,29

Climate change is another critical factor contributing to the spread of viral infections. Global increases in temperature and altered precipitation patterns are projected to lead to the emergence and expansion of tropical diseases, particularly arboviruses, into temperate regions.30 These changes in climate can alter the habitats and behaviours of disease vectors, increasing the risk of outbreaks in previously unaffected areas.

Furthermore, the world’s increasing globalisation, driven by technological advancements, has enhanced connectivity and interdependence among nations. While this interconnectedness brings numerous benefits, such as economic growth and cultural exchange, it also raises significant concerns regarding the global spread of viral pathogens.31 

 The COVID-19 pandemic highlighted these vulnerabilities, demonstrating how quickly a virus could spread across the globe regardless of geographic or political boundaries. Recent studies have shown that the more globalized a country is, the faster the transmission speed of coronavirus and the higher the fatality rates.32

Summary 

Overall, the increased recognition that the nervous system is a key target for viral pathogens has significantly expanded our understanding of disease pathophysiology. Further research should focus on elucidating the effects of viral infections on neuronal biology. This knowledge will be instrumental in developing therapeutic options, which is critical given the rising prevalence and impact of neuroinvasive viral diseases in an increasingly interconnected and climate-affected world. 

FAQs 

What treatment options are available for HIV? 

HIV is treated with antiretroviral medications which inhibit the virus's ability to replicate. This treatment allows the immune system to recover and stop further damage. To counteract the virus's ability to quickly adapt and develop resistance, a combination of HIV drugs is often used. Currently, there is no vaccine available to prevent HIV.

What treatment options are available for zika?

There is no specific treatment or preventive vaccine against ZIKV.

What treatment options are available for COVID-19? 

Extracorporeal membrane oxygenation is an efficient treatment for severe COVID-19. Vaccines were key to controlling the transmission of the virus, decreasing the severity of illness and preventing mortality. 

References

  1. Van Seventer JM, Hochberg NS. Principles of infectious diseases: transmission, diagnosis, prevention, and control. International encyclopedia of public health. 2017:22.
  2. Bloom DE, Cadarette D. Infectious disease threats in the twenty-first century: strengthening the global response. Frontiers in immunology. 2019 Mar 28;10:549.
  3. McArthur DB. Emerging infectious diseases. The Nursing Clinics of North America. 2019 Jun;54(2):297.
  4. Beckham JD, Pastula DM, Massey A, Tyler KL. Zika virus as an emerging global pathogen: neurological complications of Zika virus. JAMA neurology. 2016 Jul 1;73(7):875-9.
  5. de Laval F, d’Aubigny H, Mathéus S, Labrousse T, Ensargueix AL, Lorenzi EM, Le Flem FX, André N, Belleoud D, Leparc-Goffart I, Rousset D. Evolution of symptoms and quality of life during Zika virus infection: A 1-year prospective cohort study. Journal of Clinical Virology. 2018 Dec 1;109:57-62.
  6. Russo FB, Jungmann P, Beltrão‐Braga PC. Zika infection and the development of neurological defects. Cellular microbiology. 2017 Jun;19(6):e12744.
  7. de Melo Marques V, Santos CS, Santiago IG, Marques SM, Brasil MD, Lima TT, Costa PS. Neurological complications of congenital Zika virus infection. Pediatric neurology. 2019 Feb 1;91:3-10.
  8. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clinical immunology. 2020 Jun 1;215:108427.
  9. World Health Organisation. The true death toll of COVID-19 estimating global excess mortality [Internet]. World Health Organization; 2021 [cited 2024 May 23]. Available from: https://www.who.int/data/stories/the-true-death-toll-of-covid-19-estimating-global-excess-mortality 
  10. Naseer S, Khalid S, Parveen S, Abbass K, Song H, Achim MV. COVID-19 outbreak: Impact on global economy. Frontiers in public health. 2023 Jan 30;10:1009393.
  11. Nolen LT, Mukerji SS, Mejia NI. Post-acute neurological consequences of COVID-19: an unequal burden. Nature Medicine. 2022 Jan;28(1):20-3.
  12. Braga LW, Oliveira SB, Moreira AS, Pereira ME, Carneiro VS, Serio AS, Freitas LF, Isidro HB, Souza LM. Neuropsychological manifestations of long COVID in hospitalized and non-hospitalized Brazilian Patients. NeuroRehabilitation. 2022 Jan 1;50(4):391-400.
  13. Deeks SG, Overbaugh J, Phillips A, Buchbinder S. HIV infection. Nature reviews Disease primers. 2015 Oct 1;1(1):1-22.
  14. Lucas S, Nelson AM. HIV and the spectrum of human disease. The Journal of pathology. 2015 Jan;235(2):229-41.
  15. Tedaldi EM, Minniti NL, Fischer T. HIV-associated neurocognitive disorders: the relationship of HIV infection with physical and social comorbidities. BioMed research international. 2015 Oct;2015.
  16. Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, Mankowski JL, Brown A, Volsky DJ, McArthur JC. HIV-associated neurocognitive disorder—pathogenesis and prospects for treatment. Nature Reviews Neurology. 2016 Apr;12(4):234-48.
  17. Koyuncu OO, Hogue IB, Enquist LW. Virus infections in the nervous system. Cell host & microbe. 2013 Apr 17;13(4):379-93.
  18. Forrester JV, McMenamin PG, Dando SJ. CNS infection and immune privilege. Nature Reviews Neuroscience. 2018 Nov;19(11):655-71.
  19. Patabendige A, Janigro D. The role of the blood–brain barrier during neurological disease and infection. Biochemical Society Transactions. 2023 Apr 26;51(2):613-26.
  20. Alimonti JB, Ribecco-Lutkiewicz M, Sodja C, Jezierski A, Stanimirovic DB, Liu Q, Haqqani AS, Conlan W, Bani-Yaghoub M. Zika virus crosses an in vitro human blood brain barrier model. Fluids and Barriers of the CNS. 2018 Dec;15:1-9.
  21. Hernández-Parra H, Reyes-Hernández OD, Figueroa-González G, González-Del Carmen M, González-Torres M, Peña-Corona SI, Florán B, Cortés H, Leyva-Gómez G. Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain. Frontiers in Cellular Neuroscience. 2023 Mar 14;17:1125109.
  22. Wouk J, Rechenchoski DZ, Rodrigues BC, Ribelato EV, Faccin-Galhardi LC. Viral infections and their relationship to neurological disorders. Archives of Virology. 2021 Mar;166:733-53.
  23. Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, Yao B, Shin J, Zhang F, Lee EM, Christian KM. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell stem cell. 2016 May 5;18(5):587-90.
  24. Rothan HA, Fang S, Mahesh M, Byrareddy SN. Zika virus and the metabolism of neuronal cells. Molecular neurobiology. 2019 Apr;56(4):2551-7.
  25. Rosa-Fernandes L, Cugola FR, Russo FB, Kawahara R, de Melo Freire CC, Leite PE, Bassi Stern AC, Angeli CB, De Oliveira DB, Melo SR, Zanotto PM. Zika virus impairs neurogenesis and synaptogenesis pathways in human neural stem cells and neurons. Frontiers in cellular neuroscience. 2019 Mar 15;13:64.
  26. Sahraei M, Sahraei H. Neurological complications of corona virus: a mini-review. International Clinical Neuroscience Journal. 2022 Feb 1;9(1):e8-.
  27. Li L, Mao S, Wang J, Ding X, Zen JY. Viral infection and neurological disorders—potential role of extracellular nucleotides in neuroinflammation. ExRNA. 2019 Dec;1:1-5.
  28. Rojas-Celis V, Valiente-Echeverría F, Soto-Rifo R, Toro-Ascuy D. New challenges of HIV-1 infection: how HIV-1 attacks and resides in the central nervous system. Cells. 2019 Oct 13;8(10):1245.
  29. Hascup ER, Hascup KN. Does SARS-CoV-2 infection cause chronic neurological complications?. Geroscience. 2020 Aug;42(4):1083-7.
  30. Robert, M.A., Stewart-Ibarra, A.M. and Estallo, E.L., 2020. Climate change and viral emergence: evidence from Aedes-borne arboviruses. Current opinion in virology, 40, pp.41-47.
  31. Coe NM, Yeung HW. Global production networks: Theorizing economic development in an interconnected world. Oxford University Press; 2015.
  32. Zimmermann KF, Karabulut G, Bilgin MH, Doker AC. Inter‐country distancing, globalisation and the coronavirus pandemic. The World Economy. 2020 Jun;43(6):1484-98.

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Laura Bassett

Global Health and Development masters at UCL

Laura is an experienced researcher, advocate, and writer with a robust background in the medical writing sector. She has dedicated multiple years to writing about complex diseases, providing insightful and accessible content that bridges the gap between medical professionals and the general public.

Laura has significantly contributed to the development of health information leaflets, ensuring that crucial medical details are communicated clearly and effectively. Her expertise in research and advocacy underpins her commitment to improving patient education and healthcare communication.

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