While the COVID-19 epidemic was initially defined as a respiratory ailment, its impact on various physiological systems, including the heart and brain have become evident in recent studies. Early reports from the SARS-COV-2 cases presented signs of sudden loss of the sense of smell, a symptom suggestive of the virus’ effect on the nervous system. As more people tested positive, other neurological issues, such as stroke, emerged.
Six (6) coronaviruses were known to infect people prior to the discovery of SARS-CoV-2. Four (4) of these coronaviruses cause seasonal, mostly mild respiratory illness and have a significant global prevalence, accounting for 15–30% of upper respiratory tract infections. The other two coronaviruses have caused huge epidemics with mortality primarily from respiratory disease; SARS-CoV caused SARS in 2002–2003, and MERS-CoV caused Middle East respiratory syndrome (MERS) in 2012.
Early detection and isolation have become difficult at the onset of SARS-CoV-2 as it produces a high number of asymptomatic cases. It is critical to consider that some people with existing neurological diseases may become infected with the virus by chance and a thorough examination shall always be observed to effectively rule out other known sources of brain infections before attributing it to COVID-19.
How does COVID-19 enter and affect the brain?
Experts believe that SARS-CoV-2 could enter the brain through the olfactory mucosa, the lining of the nasal cavity that surrounds the brain. Health-care providers swab the nose to test for COVID-19 because the virus is frequently discovered in the nasal cavity.
Respiratory viruses have been investigated to have an affinity toward the nervous system cells. The loss of smell is a common symptom of COVID-19 entails that the olfactory cells concentrated in the nose are especially sensitive to viral invasion and are particularly targeted by SARS-CoV-2.
The virus can enter the brain through the olfactory cells in the nose and travel to the olfactory bulb located near the hippocampus, a part of our brain essential for short-term memory. When the virus enters the brain, its pathway has been observed to lead to the hippocampus, which may explain the cognitive impairment present in some COVID-19 patients. This movement of the virus may also play an important role in the faster cognitive deterioration of some recovered patients over time.
These observations imply that the virus is getting close to fully entering the brain. Autopsy analyses of COVID-19 patients have detected intact coronavirus particles in the supporting cells of olfactory mucosa at the roof of the nose, with signs of active replication in its tissues.
The loss of taste and smell at the onset of SARS-CoV-2 infections, a common symptom among patients, is caused by viral replication that damages and/or inflames olfactory cells. The virus might then make its way into the olfactory bulb–a hub for processing sensory information–and ultimately into the brain via certain cranial nerves.
The virus may also be entering the brain through numerous channels because of viral RNA in olfactory tissues and viral RNA and protein cells found in the medulla oblongata, the brainstem, and other regions of the brain, including the cerebellum.
An analysis involving 26 brain samples from deceased COVID-19 patients showed that five (5) brain samples had evidence of COVID-19 infection and 66% of which had infected astrocytes.
SARS-CoV-2 has been found to infect astrocytes, a type of cell found in the brain that serves a variety of roles, including supplying nourishment to neurons to keep them alive. Astrocytes accomplish a lot that promotes normal brain function and their infection can definitely interrupt a person’s life.
Studies suggest that SARS-CoV-2 preferentially infects astrocytes over other brain cells. In an experiment using small brain-like structures created from stem cells called brain organoids, SARS-CoV-2 almost entirely infected astrocytes while no other cells were affected. The infected astrocytes could explain some of the neurological symptoms linked with COVID-19, namely weariness, sadness, and “brain fog,” which includes confusion and forgetfulness.
Other researchers have been looking into how the novel coronavirus infects neurons and causes brain tissue damage. The prevalence of neurological problems is unknown, but it is safe to conclude that COVID-19 patients frequently experience neurological issues. A comprehensive review specified that the closest estimate thus far is that 30% to 50% of hospitalized people due to COVID-19 have developed neurological issues.
A study employed lab-grown, miniature 3D organ reproductions to show how SARS-CoV-2 infiltrates the brain. Through these lab-grown organoids, it was evident that COVID-19 was able to infect neurons and successfully multiply itself by increasing the metabolism of infected cells. Simultaneously, healthy, uninfected neurons near the infected ones died due to a lack of oxygen.
Since these experiments exhibit alarming manifestations of COVID-19 to the brain, scientists have also been studying ways on how to counter it. It was found that inhibiting the ACE2 receptors prevented the virus from infecting human brain organoids.
ACE2 is a protein found on the surface of many different types of cells. It is an enzyme that breaks down the bigger protein angiotensinogen to produce tiny proteins that then govern cell processes. The SARS-CoV-2 virus attaches to ACE2 via the spike-like protein on its surface, much like a key being placed into a lock, prior to cell entry and infection. As a result, ACE2 serves as a cellular entryway for COVID-19.
In an experiment involving genetically engineered mice that produce human ACE2 receptors, SARS-CoV-2 also successfully affected the mice’s brains. In this case, the virus affected the brain’s blood vessels and eventually cut off the brain’s oxygen supply. Furthermore, results displayed that the mice with infections that had spread to the brain suffered more serious conditions than mice with an infection that had just spread to the lungs.
SARS-CoV-2 was also discovered in a cortical neuron–a neuron found in the cerebral cortex of the brain–from a deceased COVID-19 patient. Infected areas were associated with ischemic infarcts, which occur when there is a lack of blood flow, resulting in tissue damage and cell death.
While neurological issues in COVID-19 individuals include anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures, the extent of neurological damage SARS-CoV-2 causes remains unknown.
Majid Futohi and his colleagues identified three (3) distinct NeuroCovid neurological categories or stages:
• Stage I: The virus damage is limited to epithelial cells in the nose and mouth.
• Stage II: Patients may experience blood clots in their brain partially caused by an inflammatory immune response called the “cytokine storm,” which can result in mini-strokes that may cause cumulative neural damage.
• Stage III: The virus has already damaged the blood-brain barrier, which protects blood vessels of the brain, causing seizures or encephalopathy.
Keeping accurate registries of COVID-19 individuals with neurological abnormalities may allow us to establish credible links with aging-associated and neurodegenerative illnesses like Parkinson’s disease in the future. It is fundamental to devise standardized assessments such as quantitative EEG, fluid biomarkers, cognitive evaluations, and multimodal neuroimaging that can further provide insight into other potential long-term neurological effects of SARS-CoV-2 such as depression, memory loss, mild cognitive impairment, or Alzheimer’s disease.
Indirect effects of COVID-19 pandemic
The COVID-19 pandemic is more than just a medical phenomenon. The sudden disruption of society and daily life caused worry, stress, anxiety, and stigma to the public. Frontliners, especially healthcare personnel, may also suffer the neurological consequences of COVID-19 in the form of stress impacts from battling the epidemic.
Frontline healthcare personnel who deal with critically ill patients are under a lot of stress. Cortisol, which is released in reaction to stress, has an indirect negative impact on the hippocampus. Our healthcare staff who are interacting with COVID-19 patients may test negative from the virus, but they may suffer long-term harm in the form of PTSD.
In a study involving 1,257 healthcare employees in 34 Chinese hospitals, 634 (50%) reported depression symptoms, 560 (45%) expressed anxiety, 427 (34%) experienced insomnia, and 899 (72%) reported distress. These symptoms were more common in women than in men, in nurses than in physicians, in Wuhan respondents than in those from other cities, and in frontline workers directly engaged in COVID-19 diagnosis/treatment or providing nursing care for affected patients than in those in other health care roles.
Because of the rapid human-to-human transmission of the SARS-CoV-2, national lockdowns were imposed to prevent the disease from spreading further. Isolation, social alienation, and the shutdown of educational institutions, jobs, and recreational venues forced people to stay at home in order to break the transmission cycle.
Some evidence of mental health issues due to COVID-19 has been published, but it still needs additional well-designed research. Most general public surveys demonstrate higher symptoms of depression, anxiety, and stress in relation to COVID-19, as a result of psychosocial stresses such as life disruption, fear of sickness, or concern of poor economic effects.
Lack of communication with family or loved ones during quarantine and hospital stays might cause psychological instability in patients with COVID-19. High rates of post-traumatic symptoms have been documented in clinically stable persons who have been discharged from the hospital after healing from COVID-19. A study involving 45 individuals who recovered from COVID-19 after being admitted to intensive-care units (ICUs) found that 15 (33%) individuals
exhibited dysexecutive syndrome following ICU discharge.
Recent findings suggest that there is a chance of a post-COVID illness similar to depression. The assumption that SARS-CoV-2 is neurotropic highlights the importance of assessing both short and long-term impacts on the nervous system.
People with pre-existing mental health difficulties may be at a higher risk of SARS-CoV-2 infection due to their living circumstances. Severe mental illness, alcohol or drug abuse, and homelessness are all risk factors for SARS-CoV-2 infection. The severe cases of COVID-19 are all related to additional risk factors such as concomitant medical problems. People with mental illnesses have a higher chance of infection in general, hence a higher risk of COVID-19.
Since the onset of the COVID-19 pandemic, people with pre-existing mental health disorders have reported increased symptoms and poorer access to mental health services and supports. Early discharge from psychiatric units and disruption of face-to-face psychiatric care have become common, with negative consequences including relapse, suicidal behavior, lack of access to medical care, and an increase in hospitalizations.
These people were extremely affected by quarantine and lockdown: heightened symptoms of anxiety and depression, as well as a high incidence of post-traumatic stress disorder and insomnia, have been recorded. Simultaneously, physical separation has diminished the availability of numerous family, social, and mental services. People with major mental illnesses and accompanying socio-economic problems are particularly vulnerable to the pandemic’s direct and indirect consequences.
Studies conducted in the United States prove that the COVID-19 pandemic has been connected with mental health issues related to the disease’s morbidity and mortality, as well as mitigation actions, such as the impact of physical distancing and stay-at-home orders. Anxiety and depression symptoms increased significantly in the United States from April to June of 2020, compared to the same time in 2019. The prevalence of anxiety disorder symptoms was
roughly three times that reported in the second quarter of 2019 (25.5% versus 8.1%), and the prevalence of depressive disorder was roughly four times that reported in the second quarter of 2019 (24.3% versus 6.5%).
Distress reactions, psychiatric disorders, and risky behaviors are some of the behavioral and psychological issues that have arisen as a result of the pandemic’s direct and indirect effects. Changes in sleep, a decreased sense of safety, irritation, distraction, social disengagement, and physical sensations are all signs of distress. Psychiatric diseases include depression, anxiety, and post-traumatic stress disorder, while risky behaviors manifest in the
increased use of alcohol and drugs, interpersonal aggression, and participation in restricted behaviors.
Where do we go from here?
One pattern of neurological consequences is unlikely to apply to all COVID-19 patients. Only a few hundred brain autopsies have been documented to date, partly due to a lack of specialist equipment and laboratories to conduct them. The myriad of neurological symptoms also needs to be organized for accuracy and precision. Diagnostic criteria for acute and chronic neurological aftermaths of COVID-19 still need to be established.
Additional research will also benefit others who suffer from neurological disorders caused by various types of illnesses. Experiences of many people with cognitive problems, brain fog, and neurological disabilities from other viral diseases such as Ebola or West Nile have generally gone unheeded. It is due time for the world to take this issue much more scientifically than it has in the past. The pursuit to understand and develop a diagnostic tool for COVID-19’s neurological impacts would be an enormous advantage for humanity.
Aside from COVID-19 positive patients, innovative resolutions to the epidemic’s impact shall also transcend to the larger population. Healthcare workers, for instance, must have sufficient access to their fundamental needs to stay safe. Our frontliners deserve to eat, drink, sleep and take enough breaks on a regular basis with encouragement and adequate access to professional help in case of signs of depression and other mental health issues.
On the other hand, the general population should be urged to utilize the media responsibly to prevent other psychosocial difficulties. Fact-checked and reputable sources such as the Ministry of Health, the Centers for Disease Control (CDC), or the World Health Organization (WHO) should be promoted as the primary source of information regarding COVID-19.
Undoubtedly, information regarding mental health issues as a product of the disruptive pandemic should be available without stigma. Knowing that there are methods to effectively cope with severe conditions can help patients, healthcare professionals, family members, and the general public to feel more normal.
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