COVID-19 has also increasingly become associated with various long-term cognitive and behavioral difficulties which are often chronic and may be permanent. Terms like “Covid Brain Fog” or “long-haulers” for people suffering from persistent symptoms, are being used to describe this phenomena.
Tens of thousands of people in the United States are being identified as post-COVID long haulers. Published studies and surveys indicate that between 50% to 80% of Covid patients continue to experience symptoms months after the onset of COVID-19, even after tests no longer detect virus in their body.
Currently, no one can accurately predict who will become a long hauler. The occurrence of these symptoms is not limited to severe symptomatic infections, but also occur even in mild or even completely asymptomatic infections. The effects of brain disorders induced by COVID-19 range from chronic exhaustion (similar to Chronic Fatigue Syndrome) to an inability to think clearly or concentrate or sustain attention. Neurological symptoms may include a feeling of disorientation or confusion, an inability to feel fully awake, mood swings or patterns of irritability or emotional lability. There is increasing evidence that there may be mild brain damage that occurs in some survivors, causing pervasive but subtle cognitive, behavioral, and psychological problems.
HOW COVID DAMAGES THE BRAIN
According to Dr. Andrew E. Budson, of Harvard Medical School, there are several ways Covid can damage the brain:
· Encephalitis, which is a rare and acute inflammation of the brain.
· Stroke - individuals over 70 years of age were at particularly high risk for stroke related to COVID infection.
· Hypoxia, or a lack of oxygen
· Damage to the brain’s immune system
IMMUNE SYSTEM DSYFUNCTION
What we are now learning, is that COVID-19 impacts the immune system which in turn can lead to damaged circuits in the brain. COVID-19 has the ability to disable or weaken our bodies first immune response, called the initial innate immune response, preventing it from working adequately. Consequently, in the absence of some of the usual early checks on viral replication the virus is able to replicate more easily. This allows the virus to quickly flood the body with a high viral load. As a result, the viral invaders may only come under full attack much later in the immune response, once the adaptive immune system is activated.
Given the advanced state of the infection, the resulting later immune response (adaptive) tends to be much stronger and more overwhelming in order to accommodate the greatly increased viral load. This situation may account for the dramatic escalation of the immune response and the resulting cytokine storm often observed in severe COVID-19 infections.
During this process, the immune system is not able to precisely target its response, as it normally would. Rather, the immune attack assumes more of an indiscriminate shotgun approach which can result in significant damage inflicted on the body’s own tissues. The resulting battle scene leaves behind a significant amount of debris in the form of destroyed virus particles and human cellular debris. If the COVID-19 infection is sufficiently severe, the immune system’s efforts to repair the areas of damaged tissue may leave long-term or permanent scarring in the form of tissue that is now quite possibly less elastic and less able to physiologically operate in the ways that the previously normal brain parenchyma (functional cell tissue) would have functioned.
The damage caused by our own immune system response is now being considered as a potential key factor leading to the Brain Fog issues observed in many long hauler patients. This is because our brains require multiple, widely separated locations of the brain cortex known as lobules to operate in concert together and with a high degree of precision. Injuries to these brain circuits may be thought of in terms of the aphorism that “A chain is only as strong as its weakest link”. If any link in this fragile chain is not adequately functioning, it affects the strength of the entire chain. As an example, a task like reading might be much more difficult or even impossible to perform. In addition, the loss of any discrete cognitive ability does not require that the entire circuit be affected. Rather, a decrease in function can result from any area of that is impaired anywhere along the length of that circuit.
Scarring and neuronal loss are likely results of a COVID-19 infection, possibly leading to impaired ATP production and depleted energy reserves in the brain. Neurons are very high energy consumers. Though the brain compromises only 2-4% of total body weight, nonetheless it accounts for 20-30% of the body’s total energy consumption. Neurons are incredibly energy-hungry, in part because they contain a large number of mitochondria. Mitochondria are the energy generating organelles of all cells. In many parts of the body such as adipose tissue, there are comparatively few mitochondria in a given cell. An individual neuron, by contrast, may contain tens of thousands of mitochondria. The need to feed so many mitochondria is one of the reasons neurons are so energy hungry.
This pattern of high energy consumption may account for the symptom pattern that Chronic Fatigue sufferers and Covid long haulers often refer to, in which they describe waking up in the morning with enough energy to concentrate or perform some simple task for, say, an hour, and then feeling so depleted that they are unable to get out of bed for the rest of the day. Such a temporal pattern of exhaustion could be explained by isolated, yet critical areas of brain injury, possibly located in the reticular activating system (RAS), for example, an area responsible for maintaining a normal state of being and feeling awake. If the RAS were to be injured by Covid infection, this could conceivably lead to significant ATP depletion upon comparatively brief exertion. This ATP depletion then, might only be alleviated quite slowly, for example, by sleeping through the night. During the subsequent downtime, including the following night's 8 hours of sleep, ATP in the affected neurons could be restored. This pattern of only having energy for a short period of time in the morning could be explained by an early rapid ATP depletion phase, followed by a much slower ATP restoration phase. This pattern might then continue as long as it takes for the brain to heal.
OTHER MENTAL HEALTH CONSQUENCES
“One of the most common mental health effects and challenges has been depression and anxiety,” said Dr. Sanghavi. medical director of the intensive care unit at Mayo Clinic in Jacksonville, Florida, “The pandemic itself has brought about a lot of challenges to the patients’ life, be it financial or personal, and add to it the recuperation from an illness like COVID. In addition to depression and anxiety, other mental health effects might be insomnia and PTSD.”
Doctors remain are still certain which treatment options might be helpful. Researchers are still struggling to understand the pathophysiology of Covid. This is still a very new disease. The answers are not clear, and certainly not simple. Even defining the problem and treatment for each patient is complicated. Post Covid clinics are popping up all over the country trying to find ways to diagnosis and help patients. “Our worry as health care providers is that we don’t know how many of these symptoms are permanent, or if there is permanent damage being done,” Dr Christine Sandrock, Professor at UC Davis, said.
PBM AND 40Hz GAMMA TREATMENTS
Photobiomodulation or Light Therapy (PBM) and Brainwave Entrainment (Flicker) are two technologies that could conceivably provide safe and effective alleviation of symptoms associated with brain fog, fatigue, insomnia, and stress, at little to no risk. The reasons for this include the following:
PBM with Red and Near Infrared (NIR) light, 600 to 700 nm, and 760 to 940 nm respectively has been shown to have various effects:
· Increase synapse formation
· Increase BDNF (supports the survival of neurons and brain cells)
· Increase glucose metabolism
· Increase antioxidant levels
· Decrease inflammation
· Decrease edema
· Decrease neuronal excitotoxicity
· Increase brain circulation through the creation of new arterial blood vessel growth
· Interact directly with the mitochondria to help generate ATP and increase mitochondrial membrane potential, O2 consumption, all of which promotes energy generation and mitochondrial metabolic health for the efficient transport of energy within cells.
· PBM has also been shown to help address chronic fatigue in other non-COVID-19 settings
40hz Gamma Flicker delivered via synchronized light and sound has also been shown in U.S. university studies to increase microglial activity (microglia are the phagocytic cells of the brain's immune system), specifically by improving phagocytosis (removal) of parenchymal and cellular debris and pathogens. Gamma flicker has also been shown to facilitate the repair and/or resumption of neuronal functions in 5xFAD mice.
Possibly one of the most significant capabilities of PBM, in regard to its suitability for treating post COVID-19 brain fog or other sorts of cognitive impairment, is its ability, specifically when using the Red and Near-Infraredwavelengths, to penetrate the brain to a depth of up to one centimeter. This factor allows the light to hit a substantial portion of the cortical neurons, as well as some of the neurons making up long tract fibers of important brain circuits. Furthermore, PBM not only reaches these tissues, but also interacts with them in an amazing way by directly causing physiologic changes within the mitochondria.
Mitochondria contain important intracellular organelles known as cytochromes, which have the ability to absorb visible light energy and use the absorbed energy to generate ATP. Light, especially Red and Near-Infrared wavelengths, is capable of activating cytochrome C oxidase in ways previously well described by others, thereby helping to facilitate the creation of ATP. This ATP can be thought of as the little packets of electrochemical energy that serve as the currency, in terms of molecular energy, in many areas of cellular metabolism.
Recent research conducted by Singer et al. explored the ability of the combination of Gamma light and sound to affect microglia cells. That research featured genetically altered 5xFAD mice, which are known to develop Aβ plaques and phosphorylated tau tangles at a very accelerated rate similar to that seen in humans with Alzheimer’s disease (AD). For reasons that remain unclear, it appears from this research that the microglia of these 5xFAD mice prematurely cease their regular function of cleaning up the brain parenchyma. It was thus speculated that this might be one reason that AD brains become increasingly less able to function normally. In these experiments, Singer decided to expose these mice to externally produced light and sound. The light was flickered at a frequency of 40 Hz (in the gamma frequency range), and the sound was pulsed at the same frequency in a synchronized fashion. When these mice were exposed to these stimuli, the results were astounding. For reasons that are still to be elucidated, the rodent microglia began functioning again, the clean up of their brains resumed, reduced levels of Aβ plaques, and demonstrated other changes suggestive of improved microglial functioning.
A similar, preliminary study was then conducted on human subjects who had Minimal Cognitive Impairment (MCI). In this study, the human subjects were equipped with special goggles and earphones that exposed them to 40 Hz gamma light and sound for sessions lasting an hour a day. The study appears to show that synchronized light and sound flickering at 40 Hz is capable of changing cytokine levels in the human body. The significance of these changes in cytokine levels has yet to be elucidated in any detail. However, the treatment with 40 Hz gamma light and sound has shown to improve a number of cognitive symptoms in the subjects, thus underscoring the potential that light and sound therapy has for improving cognitive function in humans.
Light therapy applications have also been successfully used to reset circadian rhythms and improve sleep, in the treatment for concussions and TBI (Traumatic Brain Injury), to accelerate muscle recovery after exertion, and to stimulate tissue repair.
Nuzzo, D. and P. Picone, Potential neurological effects of severe COVID-19 infection. Neuroscience research, 2020. 158: p. 1-5.
Komaroff, A.L. and L. Bateman, Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Frontiers in Medicine, 2021. 7.
Perrin, R., et al., Into the looking glass: Post-viral syndrome post COVID-19. Medical Hypotheses, 2020. 144: p. 110055.
Vink, M. and A. Vink-Niese, Could Cognitive Behavioral Therapy Be an Effective Treatment for Long COVID and Post COVID-19 Fatigue Syndrome? Lessons from the Qure Study for Q-Fever Fatigue Syndrome. Healthcare, 2020. 8(4): p. 552.
Townsend, L., et al., Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLOS ONE, 2020. 15(11): p. e0240784.
Geppert, C.M.A., The Brain in COVID-19: No One Is Okay. Federal Practitioner, 2020(Vol 37 No 9).
Orsucci, D., et al., Neurological features of COVID-19 and their treatment: a review. Drugs in Context, 2020. 9: p. 1-12.Nuzzo, D. and P. Picone, Potential neurological effects of severe COVID-19 infection. Neuroscience research, 2020. 158: p. 1-5.
Hamblin, M.R. and Y.-Y. Huang, Photobiomodulation in the brain : low-level laser (light) therapy in neurology and neuroscience. 1. ed. 2019, Waltham: Elsevier. pages cm.
Iaccarino, H.F., et al., Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature, 2016. 540(7632): p. 230-235.
Singer, A.C., et al., Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load. Nature Protocols, 2018. 13(8): p. 1850-1868.
Budson, A.E., The hidden long-term cognitive effects of COVID-19, Harvard Health Publishing, 2020
Komaroff, A., The tragedy of long COVID, Harvard Health Publishing, 2020
Cari, A., et al., Persistent Symptoms in Patients After Acute COVID-19, JAMA. 2020
Berg, S., COVID long-haulers: Questions patients have about symptoms, AMA, 2021
Coronavirus, UC Davis Health, 2021