Neurological Complications and Conditions Resulting from SARS-CoV-2 Infection (COVID-19)

There have been many articles published about neurological sequelae following SARS-CoV-2 infection. In this blog post, we will review two recent papers (“Neurological Complications caused by SARS-CoV-2”, Neurological complications caused by SARS-CoV-2 (asm.org), appearing in Clinical Microbiology Reviews and “Cognitive and Psychiatric Symptom Trajectories 2 – 3 years after Hospital Admission for COVID-19: A Longitudinal, Prospective Cohort Study in the UK”, Cognitive and psychiatric symptom trajectories 2–3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK – The Lancet Psychiatry, appearing in The Lancet Psychiatry) that summarize much of what we have learned thus far (I have no doubt that we will learn much more in the next ten years) about the neurological sequelae that some people suffer following SARS-CoV-2 infection.

It is notable that as many as 30 percent of patients with COVID-19 present with neurological symptoms. For some time now, we have had evidence that the SARS-CoV-2 virus can infect the brain based upon the findings at autopsy in patients who died from COVID-19 that the viral genetic material could be found within cells of the brain and within the cerebral spinal fluid. It has been clear for some time now that we can see acute infection present with neurological impairments, or neurologic complications can occur weeks to months following seeming recovery from the infection, as well as part of the constellation of symptoms and conditions that occur in association with Long COVID.

There have been a number of mechanisms for SARS-CoV-2 infection of the brain proposed, including the virus entering the neurons of the olfactory nerve at the back of the nose and travelling up the nerve (retrograde neuronal spread) to the brain, spread to the brain during the brief period of time that the virus gets into the bloodstream (hematogenous spread), disruption of the blood brain barrier that normally makes it harder for infectious agents to get access to the brain by multiple mechanisms, including through cytokine storm that has been associated with severe cases of COVID-19 in children and adults, and neuronal fusion by which SARS-CoV-2 infection of one neuron may cause the neuron to abnormally fuse to another neuron allowing the virus to freely move between the fused neurons. SARS-CoV-2 has also been capable of causing neurological complications and conditions other than by direct infection of the brain cells by causing blockages in blood vessels that supply blood to or drain blood from the brain or by the formation of blood clots that travel in the blood stream to the brain, causing a lack of oxygenation (hypoxia) to a portion of the brain resulting in tissue injury or death of brain tissue and neurological deficits related to the particular brain function conducted by the affected part of the brain.

Depending upon the parts of the brain affected and the extent of the involvement, patients with COVID-19 may experience headache, loss of smell or altered smell, loss of taste or altered taste, a range of visual disturbances, sudden weakness or loss of movement of an extremity, confusion, altered mental status (level of cognition or alertness or both), seizures, abnormal movements, dizziness, imbalance, slurred speech or inability to speak, altered gait, tremors, slow movements, increased muscle tone, and impaired memory, persistent ringing in the ears, loss of hearing, among other neurological signs and symptoms.

These signs and symptoms can be manifestations of meningitis, encephalitis, encephalopathy, ischemic or hemorrhagic stroke, and Parkinson’s Disease among others. Further, it has been well established that those at risk of dementia or with early stages of dementia experience an acceleration and worsening of dementia following COVID-19. There has been mounting evidence that SAR-CoV-2 infection of the brain can result in dementia and pathological findings that very closely resemble Alzheimer’s Disease.

There is mounting evidence that those who develop loss of smell with their SARS-CoV-2 infection may be at increased risk of developing neurologic sequelae and neurodegenerative conditions following their COVID-19 illness. We don’t know how long following infection persons may remain at risk for neurological conditions; however, we are gaining mounting evidence that prior infection with certain viruses may cause neurological problems many years later in life, e.g., enterovirus and human herpes virus with amyotrophic lateral sclerosis (ALS), influenza virus with Parkinson’s disease, and Epstein-Barr virus with multiple sclerosis (MS). For a more extensive review of this topic, see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838016/.

“Brain fog” remains one of the most frequent neurological complaints of Long COVID patients encompassing such things as diminished ability to concentrate and focus, confusion, short-term memory loss and/or decreased mental acuity, and cognitive impairments can often be detected on testing.

Patients with preexisting neurological conditions may be particularly at risk for neurological deterioration with SARS-CoV-2 infection, particularly those with Parkinson’s disease or those who are at risk for dementia or have early onset dementia.

Those persons who were hospitalized due to severe COVID-19 may be at particular risk for neurological sequelae. A study of such patients demonstrated that slightly more than half reported awareness of cognitive decline, while all patients tested had worse cognitive scores among all domains of cognitive testing following discharge from the hospital when compared to healthy controls adjusted for sociodemographic factors. In addition, roughly three-quarters of patients reported at least mild depression, a little more than half reported anxiety, and more than a fifth of all patients reported severe depression. Of great concern was the fact that depression, anxiety and fatigue were worse in this group of patients at 2 – 3 years following their illness than they were at either 6 months or 12 months in this patient population, including the occurrence of new symptoms among some patients. Just short of 27 percent of these patients reported an occupational change, most commonly attributed to their poor health, and most commonly and specifically based upon cognitive decline.

There are many potential complications and conditions that can follow SARS-CoV-2 infection. Many of these are distressing and life-altering. In this blog post, I discuss some of these complications and conditions that are neurological or psychiatric in nature. I will discuss other complications and conditions in subsequent blog posts. Given that we cannot predict with confidence who will and who will not develop these conditions, the public would be well-advised to consider the potential for these health consequences in addition to simply the risk for severe COVID-19 or death when considering risk mitigation strategies and COVID-19 immunizations.