Coronavirus (CoV) is an enveloped virus with a large positive-sense, single-stranded RNA genome belonging to the Coronaviridae family; examples of CoV are SARS, MERS and now COVID-19.
It’s important to note that increased evidence shows that coronaviruses are not always confined to the respiratory tract. In fact, it may also invade the central nervous system and subsequently induce neurological diseases. The infection with SARS‐CoV has been reported in the brains of both human patients and laboratory animals where the brainstem was heavily infected, indicating the virus invades the nervous system. If the medulla (or brainstem) becomes involved, this could be another explanation for the respiratory decline that has been observed in the past and as well as the present iterations of the virus.
Other studies have indicated that coronaviruses are also associated with central nervous system (CNS) diseases such as acute disseminated encephalomyelitis and multiple sclerosis. A 2016 investigation looked at two groups (183 and 236 hospitalized children), with acute encephalitis-like syndrome and respiratory tract infection, respectively; the pediatric patients were screened for anti-CoV IgM antibodies and findings showed the expression profiles of multiple cytokines were determined in CoV-positive patients with a high incidence of CoV infection in hospitalized children particularly with CNS illness.
But what about THIS Coronavirus?
Recently, a study posted in medRxiv - The Preprint Server for Health Sciences, (see references at end of article) has reported neurological manifestations in COVID-19 in the current outbreak that involved 214 patients, of which 78 (36.4%) patients had neurologic manifestations, which affirms the rationale of the neurotropic potential in the COVID-19 virus.
In a review article first published February 27, Yan-Chao Li of Jilin University in China and colleagues argue that if SARS-CoV-2 infects nerve cells, particularly neurons in the medulla oblongata, which is part of the brain stem that serves as the control center for the heart and the lungs, the damage could contribute to “acute respiratory failure of patients with COVID-19.”
One of the papers, a review published March 13, 2020, mentioned that SARS-CoV-2, like other coronaviruses such as SARS-CoV and MERS-CoV, could target the central nervous system, possibly infecting neurons in the nasal passage and disrupting the senses of smell and taste or the other plausible explanation in inflammation driven by the viral pathophysiology.
Total loss of smell, called anosmia, can be caused by many viruses, including various strains of both coronaviruses and rhinoviruses, both of which can cause the common cold. Hyposmia, the partial loss of smell as well as anosmia may be accompanied by dysgeusia, the loss of taste. Either of these sensory losses have been reported in patients with COVID 19 and in some patients can be present in the asymptomatic phase of the illness and may be the first sign of COVID 19. Other neurological symptoms that have been noted with COVID 19 include headache, nausea, and vomiting exclusive of other gastrointestinal signs.
There is at this writing one case report of a patient with this disease that presented with an acute encephalopathy. It appears that any neurological symptom should be considered as a consequence.
In Bejing, there have been other reported cases of patients presenting with alteration of consciousness. Testing of the cerebrospinal fluid confirmed novel coronavirus as well as a diagnosis of encephalitis, an inflammation of the brain.
The brain under siege: what are the mechanisms?
SARS-CoV-2 enters human cells using a receptor called ACE2. Researchers have reported that ACE2 regulates cardiovascular function, and according to a search of protein databases, many human cell types express ACE2, including lung, heart, kidney, intestine, and brain tissue. The brain has been reported to express ACE2 receptors that have been detected over glial cells and neurons, which makes them a potential target of COVID-19.
ACE receptors line in blood vessel lining and thru this mechanism might breach the blood brain barrier and allow viral access to the brain
The blood-brain barrier, or BBB, is a single-layered lattice of cells joined together by tight junctions that keep most substances from crossing this barrier into the brain. It was once thought to be impenetrable, but now we know that there is an “ebb and flow” of toxins, pathogens, inflammatory cells and other harmful elements that are in fact crossing into and traversing the central nervous system over the course of our lives. Many factors affect the integrity of the BBB including diet, sleep, environmental influences, infections, EMFs, leaky gut syndrome and more. All of that means our brains are essentially under siege far more regularly than we may have ever realized, particularly given the toxic world in which we live.
transgenic mice expressing human ACE2 through neurons in the nose. The virus then rapidly spread to connecting nerve cells. The extensive nerve damage was the major cause of death, the team reported, even though low levels of the virus were detected in the animals’ lungs. Anosmia occurred, with the olfactory neuronal pathways identified as the source of neuro-inflammation.
In research conducted in PANS and PANDAS/autoimmune encephalitis, this neuronal highway to the brain has been studied in detail. Once an infectious pathogen or inflammatory cells (TH1 lymphocytes) is allowed entry via this route, the olfactory cortex becomes damaged and results in loss of sense of smell and sometimes taste. Neighboring structures like the frontal and temporal lobes, basal ganglia and limbic system also become affected, manifesting in a wide variety of symptoms from headache, depression and anxiety to OCD, memory impairment and movement abnormalities. Anosmia is not uncommon in neurodegenerative diseases such as Alzheimer’s and multiple sclerosis (MS). Recent studies have also established anosmia as a prodromal biomarker for Alzheimer’s disease and the presence of olfactory deficits in a subset of MS patients correlating with symptom severity.
Perhaps we should rephrase Hippocrates’ statement from “all disease begins in the gut” to all disease begins in the gut AND the nose.
Viruses with neurotropic potential: do they lead to neurodegenerative disease?
One of the earliest links between influenza viruses and neural dysfunction was a correlation between the 1918 Spanish flu, caused by a subtype called H1N1, and an epidemic of Parkinson’s a few decades later. This was termed post-encephalitic Parkinson’s (also known as sleeping sickness or von Economo encephalitis). In the 1940s and early 1950s, diagnoses of the neurodegenerative disease abruptly appeared to increase, from 1 to 2 percent of the U.S. population to 2.5 to 3 percent before declining to its original level. But the increase during those years represented 50 percent more people who subsequently developed Parkinson’s disease.
Viruses can induce brain dysfunction by either direct cytolytic effects or bystander inflammatory reactions. To date, there is evidence of systemic viral infections that occur with every neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, autism spectrum disorders, autoimmune encephalitis and PANS and PANDAS. It is has been found that neuroinflammation plays a critical role in priming vulnerable neuronal populations for subsequent degeneration.
What does the future hold?
No one really knows at this moment what the post-recovery outcomes will be after this pandemic subsides.
Will there be a rise in neurodegenerative disease?
Will we see rates of neuropsychiatric disease including depression increase? There already exist numerous studies that clearly show depression rates soaring after infections.
Only time will tell what or if there will be neurological sequalae to COVID-19.
No doubt, the additional physical and environmental stressors imposed on a global scale will bear close examination for years to come.
In hope and healing,
Dr. Suzanne Gazda
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These 17 lymphocytes drive vascular and neuronal deficits in a mouse model of postinfectious
Maryann P. Platta,b, Kevin A. Boldingc, Charlotte R. Wayneb,d, Sarah Chaudhryb, Tyler Cutforthb, Kevin M. Franksc, and Dritan Agalliub, www.pnas.org/cgi/doi/10.1073/pnas.1911097117
by Suzanne Gazda M.D.