Since the pandemic’s onset almost a year ago, an array of COVID-19 related neurological symptoms have emerged. A neurological component to the virus is now widely accepted; however, the exact role that the virus plays in triggering neurological manifestations is yet to be understood. Given the ever-growing scale of the outbreak, COVID-19’s neural-invasivity could be catastrophic. Rose Dodd investigates.
Over recent months, the number of COVID-19 cases in the UK has risen by tens of thousands. After a hopeful summer, the R number quantifying the rate of transmission rocketed to a value well over 1.0 meaning each contagious person was spreading the virus to multiple people. The government have enforced an array of strategies attempting to slow the spread , a premiliminary system that has been tried and failed… and tried again following a second national lockdown that lasted a brief month. Despite efforts to curb rising cases numbers, cases have continued to soar, hitting record-breaking figures daily.
It was initially suspected that the viral pathogen responsible for COVID-19, SARS-CoV-2, would primarily target the respiratory system. This stemmed from diagnosed patient’s symptomatic presentations; typically displaying a dry and continuous cough, breathlessness and feverous temperatures, and more severe cases exhibiting impeding breathing problems and pneumonia.
Assumptions about the virus’s respiratory nature borrowed credibility from sister pathogen – responsible for the SARS outbreak in 2003 – SARS-CoV’s mechanism of action which does target the respiratory system predominantly.
The development of easier, faster and above all, more readily available testing, brought to light that approximately 80% of cases are mild or asymptomatic, with respiratory symptoms occurring in a minority of cases. This meaning that there are likely many more cases than records suggest.
As cases continued to amass, obscure and unexpected symptoms of a wider variety began to accumulate. Reports of neurological manifestations such as a short or long term loss or change in one’s sense of smell or taste became increasingly apparent.
By May, an abnormal sense of smell was reportedly occurring in approximately 90% of cases and in the absence of respiratory symptomatology. It was then classified as a key indicator of infection.
Further neurological symptoms in COVID-positive patients have since been observed in hospitals worldwide, these including changes in the brain network (encephalopathy), brain inflammation (encephalitis), strokes, and Guillain Barré syndrome whereby the body’s immune system attacks itself causing nerve damage and muscle weakness.
Such conditions impair neurological state and function, branded by cognitive, psychiatric and behavioural prodromes, like confusion, delirium, dizziness, altered consciousness, and flu-like symptoms such as headaches and fevers; all symptoms that are similar to our by-now-familiar foe, COVID-19.
Concerning realities were unveiled during a brain-driven investigation conducted by Dr Michael Zandi and colleagues at University College London Hospital and the neighbouring National Hospital for Neurology and Neurosurgery, involving 43 COVID patients of mixed ages. In the cohort of 43, scientists recorded 8 strokes, 8 cases of Guillain Barré syndrome, and 12 cases of brain inflammation.
The frequency and extent of brain damage observed in the COVID-positive group were much greater than anticipated; sparking concern that this might be the case within the general population.
Dr Zandi said, “We identified a higher than expected number of people with neurological conditions such as brain inflammation, not always correlating with the severity of respiratory symptoms.”
Within the group, a disproportionately large 9 of 12 encephalitis patients also suffered acute disseminated encephalomyelitis, or ADEM, a rare autoimmune disease. ADEM can follow viral invasion into the peripheral nervous, central nervous and immune systems. 85% of ADEM victims recover, but those who don’t can be left with lasting neurological impairments.
The relative risk of strokes has shifted from 1% to 6% in COVID patients, and strokes have been observed in mild cases, younger patients and in patients with no typical vascular risk factors. The reasoning behind COVID related cerebrovascular events is yet to be understood. Could the virus be capable of adjusting hypercoagulability, forming clots and causing strokes?
Alterations to smell or taste are common of respiratory dysfunction, often seen with the common cold or flu. But, alongside other neurological conditions, these abnormalities are key indicators of brain dysfunction and damage and are suggestive that the virus could possess the aptitude to invade and attack the brain.
Viral invasion into the brain can be confirmed by detecting whether the virus is present in the cerebrospinal fluid, a protective and nutrient-filled fluid surrounding the brain and spine.
Reassuringly, the UCL-based study found no traces of SARS-CoV-2 in the cerebrospinal fluid, suggesting neurological manifestations could be secondary to another activated process such as the inflammatory response.
Contrariwise, at Bejing Ditan Hospital, genome sequencing revealed SARS-CoV-2 in the cerebrospinal fluid of a COVID-linked brain inflammation patient. Such results have since been repeated.
Evidence remains too limited to conclusively determine the exact cause of the neurological symptoms witnessed in COVID-19 patients. Whilst investigations are underway, it is not yet possible to rule out neural-invasivity.
SARS-CoV and SARS-CoV-2 belong to the same viral family, the coronaviruses, meaning they likely share certain behaviours. Whilst SARS-CoV is a respiratory virus, it possesses machinery that permits it entry into the nervous system, infecting the brain and affecting its function. Perhaps then, SARS-CoV-2 also does, meaning the neurological symptoms exhibited by COVID patients are the result of the virus invading the brain, as opposed to being secondary to respiratory impediments or the body’s immune response.
The severity of COVID-19’s neurological component has largely flown under the radar. This is in part because neurological symptoms are harder to observe, but also because the necessity for rapid action meant that obscure symptoms were underestimated, and functional damage that neurological malfunctions inflict can take years to fully manifest.
Scientists from multiple study groups have suggested that neurological manifestations occur in just a small fraction of cases, both symptomatic and asymptomatic (a precise fraction is yet to be elucidated). But, with well over 80 million cases confirmed worldwide, hundreds of thousands of people face neurological treachery.
Neurological damage is generally semi-permanent, however, occasionally it can be permanent, irreversible or progressively worsening. Thus, making it quite possible that damage to the nervous system and brain could be even more devastating than that to the lungs.
Whilst people have made full recoveries, returning to normal in a matter of weeks post-infection, this has not been the case for all. The term ‘long COVID’ was recently coined for the permanent repercussions associated with the virus; lasting changes to smell and taste, fatigue, headaches, lung damage and breathing difficulties and more. It’s now thought that 1 in 20 infected will suffer from long COVID. Some of the implications seen in long COVID are likely the result of permanent neurological damage.
People who’ve not yet regained their smell or taste could necessitate rehabilitation programmes to retrain, repair and regenerate damaged nerves, cells, receptors and neural circuits.
The value of sensations like smell and taste are often underestimated. Whilst in possession of such luxuries, it’s easy to take them for granted. Senses like touch, sight, smell and taste are bridges, connecting us to the world around us. A life with no flavour, no fragrance… just imagine it. People will be left unable to taste the jam on their toast nor smell their favourite perfume, facing an indefinite diminuendo to their sensory environment and consequently, their mental health and quality of life.
This isn’t the only example of COVID-related impairments to psychiatric wellbeing. It’s no surprise that we’re seeing a blanket depression across the nation… across the world, when the only certainty we have is uncertainty. Time has so far revealed that 1 in 5 confirmed COVID patients are later diagnosed with mental illness. Maybe melancholy and psychiatric unrest are more subtle symptoms of long COVID, triggered by a virally-altered brain, and disguised and exacerbated by the unpredictable socioeconomic circumstances under which so many are living.
Might the neurological effects of COVID-19 have amplified Boris Johnson’s lack of form and dithering? Will Prince Charles be able to taste his quail eggs again? What does a society do if there are widespread cognitive, psychiatric and behavioural impairments?
Whilst overwhelmed amidst the epicentre of the pandemic, we are yet to discover the full extent of the virus’s enduring aftermath. It seems COVID-19 could be more pernicious than we are already struggling to accept