Can COVID-19 infection cause Parkinson 's disease? How to treat long-term COVID symptoms of early Parkinsonism-like disease?
- Long Covid Classified Treatment Options
- 10 Oct, 2022
Numerous studies have confirmed that novel coronavirus infection in humans produced long-lasting side effects even after the symptoms of the initial infection disappeared completely, which we call long-term COVID symptoms. These effects of post-coronavirus remnants mainly were the appearance of brain fog, fatigue, shortness of breath, chronic pain, loss of smell, loss of taste, early symptoms Parkinsonism-like, early symptoms of Alzheimer 's-like disease and diarrhea. These long COVID symptoms can put eternal side effects on the body.
In this paper, the authors studied long COVID,finding that some long-term COVID syndromes were partially early Parkinsonism-like disease. This article summarized the long-term COVID syndromes of early Parkinsonism-like disease and gave in-house self assessment to judge whether people developed these symptoms of Parkinson’s disease. Then, the pathogenesis of symptoms of Parkinsonism-like disease caused by long COVID was analyzed, and the therapeutic ideas of western medicine for the disease after infection with COVID-19 were given.
Due to the limitation of western medicine treatment against long-term COVID-19 symptoms of early Parkinson's disease, this paper also recommended some traditional Chinese medicine, including Chinese medicine formula and acupuncture treatment, to treat the related symptoms of early Parkinson's disease. In addition, this paper made advises patients with long-term COVID of early Parkinson's disease on taking health care products, as well as on exercise, diet, and sleep. In the end, we hope that the treatment program for long-term COVID-19 symptoms of early Parkinson's disease suggested in this paper could benefit patients by improving their symptoms of early Parkinson's disease as soon as possible, and even cure theses symptoms caused by novel coronavirus.
Keywords: Long COVID, Post Covid, Post Covid-19 Symptoms of Parkinsonism-like disease, parkinsonian symptoms after Covid-19 infection, early Parkinson 's disease induced by Covid-19
1.What are the manifestations of long-term COVID symptoms of early Parkinsonism-like disease?
Since the COVID-19 pandemic, many people have been infected with novel coronavirus with a large number of patients with post COVID have emerged. A small number of people presented with early symptoms of Parkinson 's disease, which were sometimes continuous, but sometimes intermittent, and usually lasted for a long time, even more than two years. According to the results of large-scale case statistics in the latest study report, among people over the age of 70, people infected with COVID-19 within a year were 70% more likely to develop Parkinson's disease and Alzheimer's disease than people who didn’t infect with the COVID-19.
From the analysis of clinical cases and the conclusions of medical research papers, it can be seen that novel coronavirus infection can greatly increase the probability of Parkinson 's disease in humans.Some long-term COVID symptoms overlap with early Parkinson 's disease symptoms. If the patients infected with the long-term COVID don’t recovered, they are likely to develop Parkinson' s disease.
According to the published medical papers on long-term COVID symptoms and early Parkinson 's disease, We conclude that Long COVID and early Parkinson's symptoms overlap in the following.
(1)Body limbs become inflexible: people become tired and do not like movement, bradykinesia, body limbs become inflexible, joints do not easily bend, and take activities with a sense of retardation. Walking stride become smaller.
(2) Chronic Joint Pain: neck pain, back pain, buttock pain.
(3) Gait Freeze: difficulty in starting, difficulty in stopping, freezing of gait, and wiping of small gait.
(4)Sleep disorder: difficulty in falling asleep,easy to wake up, poor sleep quality, or feel drowsiness and it is difficult to wake up.The patient presented with the conditions of day and night reversal, staying up late, and feeling tired in the daytime and energetic at night.
2.How to judge whether people suffered the long-term COVID symptoms?
What are Post Covid-19 Symptoms (namely: Post Covid-19 Symptoms or Long Covid)? According to the definition of the World Health Organization, Post Covid-19 Symptoms or Long Covid, also known as Post Covid-19 syndrome, refers to since the patient was infected with the new coronavirus, the results of his PCR showed positive as criteria, and he still suffers uncomfortable symptoms after 3months. More detailed updated statistical information on the incidence of Post Covid-19 Symptoms according to the timeline can be found in the figure below.
Post Covid-19 Symptoms are mainly concentrated in five aspects, including respiratory syndrome, cognitive system syndrome, chronic fatigue syndrome, chronic pain syndrome, and mental syndrome, such as long-term COVID-19 symptoms of brain fog, which belongs to the cognitive system syndrome. Long-term COVID-19 symptoms of chronic fatigue are one of chronic fatigue syndrome. According to medical classification, the coincident symptoms of long-term COVID symptoms and Parkinson 's disease should be classified as neurological disorders.
If you have a history of the novel coronavirus, which means your previous result of PCR test showed positive, and before infection with the novel coronavirus, you didn’t suffer from Parkinson 's disease, but now you are presenting these symptoms of Parkinson 's disease in the above section, you are likely to afflict by Post Covid-19 Symptoms of early Parkinson 's disease.
3.What are the causes of early Parkinson 's disease after the COVID-19 infection?
According to published research papers on long-term COVID-19 symptoms, medical papers on cognitive dysfunction and cranial nerves, we found that long-term COVID-19 of brain symptoms are often associated with immune responses.
Immune response refers to the body 's defense response to foreign components or variant autologous components. Immunoreactions can be divided into non-specific immune responses and specific immune responses. Nonspecific immunity constitutes the first line of defense function of the human body and synergizes and participates in specific immune responses. Specific immune responses may manifest as normal physiological responses, abnormal pathological responses, and immune tolerance. According to different mediators of mediated effector response, specific immune response can be divided into T cell-mediated cellular immune response and B cell-mediated humoral immune response.
We concluded that the pathogenesis of symptoms of early Parkinson 's disease after long-term novel coronavirus infection can be explained according to the following development path:
(1) First, the response of the human immune system to the site of novel coronavirus infection is divided into two stages. In the preliminary stage, the immune system mobilizes macrophages and polymorphonuclear phagocytes (e.g., neutrophils, basophils, eosinophils) to rapidly reach the site of infection to control infection. In the following stages, the immune system of the human body takes about 4 days to establish adaptive immune mechanisms through learning, including T cell-mediated immune mechanisms to solve the infection, and the production B system-mediated antibody to clear the pathogen- the novel coronavirus, so as to prevent reinfection.
(2) Second, because novel coronavirus can easily mutate, so far as more and more coronavirus variants appear, and the ability of immune escape is increasing, this makes the effect decrease when the antigens (HLA) produced by the human immune system to clear novel coronavirus, which means there will be a small number of novel coronavirus immune escape. Novel coronavirus in some patients has not yet been completely cleared, but because the human immune system is suppressing these coronaviruses, leading the content of novel coronavirus too small to make PCR tests negative.
(3) Third, there are trace viruses that escaped in the human body in the long term, which will persistently infect and invade human tissue cells, causing tissue damage. Tissue damage, in turn, triggers chronic inflammation. This chronic inflammation is produced by a persistent immune response, also causing persistent massive cytokine diffusion.
(4) The continuous breakdown of a large number of cytokine proteins can lead to autoimmunity. Autoimmunity refers to the immune response produced by organisms against healthy cells and tissues of their bodies. Any disease caused by this immune abnormality is called autoimmune disease.
(5) The persistence of trace novel coronavirus continues to deteriorate the situation, leading to T cell failure and immune memory defects. Defects in immune memory can make the immune system gradually insensitive to immune pathways that eliminate novel coronavirus, eventually becoming a coexisting state. This condition is characterized by generalized diffuse chronic inflammation. In the long run, the function of body organs and tissues is reduced.
(6) For patients infected with novel coronaries, some people experienced the virus breaking through the blood-brain barrier and invading nerve cells in the brain. Evidence has been found that novel coronavirus triggers neuroinflammation and neurodegeneration in the brain. This condition can further cause metabolic abnormalities in the brain, such as capillary microthrombi in the brain, nerve cell hypoxia in brain, and so on, which may be one of the causes of long-term symptoms of cognitive dysfunction.
(7) Studies have shown that patients infected with novel coronavirus infection can trigger inflammation of the olfactory bulb or even atrophy of the olfactory bulb if the virus further invades epithelial cells in the olfactory bulb, such as capillary epithelial cells, which disrupts the transmission of electrical signals between olfactory neuron cells and mitral neuron cells. If the virus further invades the olfactory brain, it is the part of the limbic system responsible for the logical processing of encoding and decoding olfactory electrical signals. This makes the electrical signals of the olfactory nervous system unable to be normally understood and operationalized by the brain, which is one of the causes of cognitive dysfunction.
From the above pathological deduction steps, COVID-19 infection triggers an inflammatory response in the brain, which in turn produces a series of neurodegenerative lesions, which is the long-term COVID symptoms that are the cause of early Parkinson's disease symptoms. The following six medical research results can also provide evidence that COVID-19 infections have a significantly increased likelihood of causing Parkinson's disease in humans:
(1) Douaud et al. investigated structural brain changes before and after SARS-CoV-2 infection in a large sample of British Biobank participants and revealed significant reductions in gray matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus, as well as significant functional changes in brain regions connected to the primary olfactory cortex.
(2) Guedj and Sollini et al. made another study in 2021 to find that images obtained from positron emission tomography (PET) brains of patients with long-term coronavirus disease (Long COVID patients) showed inefficient metabolism of the olfactory brain, including the olfactory gyrus and connected limbic/paralimbic regions, extending to the brainstem and cerebellum (Guedj et al., 2021), as well as inefficient metabolism of the right parahippocampal gyrus and right thalamus (Sollini et al., 2021).
(3) Regarding neuroinflammation occurring in the olfactory system of COVID-19 patients, Schwabenland et al. (2021) performed a deep spatial analysis of local immune responses by imaging mass spectrometers and revealed significant immune activation in the medulla oblongata and olfactory bulb, with CD8 + T cells-microglia, mediating significant crosstalk in parenchymal cells. Mediation referred to the use of a substance as a medium to transfer the donor to the recipient, thereby changing the genotype and phenotype of the recipient. The substance utilized was the "medium" and the transfer process was called "transduction".
(4) there were also multiple investigators (Emmi et al., 2021; Matschke et al., 2020; Solomon et al., 2020) who detected significant astrogliosis, microglial activation, and microglial nodules in the brainstem and olfactory structures of COVID-19 subjects. These were evidence of brain inflammation.
(5) Elderly patients with long-term COVID-19 symptoms has also been found by investigators (Alexander D. Cohen et al., 2022), with significantly reduced vascular connectivity in areas of low cerebrovascular reactivity.
(6) Studies have shown that,the causes of symptoms related to the brain in people with very healthy brains experienced after COVID-19 infection, more likely to be autoimmune diseases(diseases in which the body 's immune system attacked their normal cells, which was a problem highlighted by the decrease in normal immune capacity, while abnormal immune capacity increase.) caused by blood-borne immune mediators (T-cell mediated cellular immune response and B-cell mediated humoral immune response) , and abnormal transsynaptic gene expression in mitral neuron cells caused by olfactory bulb dysfunction, which in turn leads to abnormal transmission of brain electrical signals.
Therefore, when we suffer from long-term COVID symptoms, do not be careless, but carefully feel the symptoms to find whether they are as same as early Parkinson's disease symptoms. If the they are same, you had better seek medical attention as soon as possible. The earlier Parkinson 's disease is detected and treated, the easier it is to control the deterioration of the disease and even cure it.
4.How to treat the long-term COVID symptoms of Parkinsonism-like?
At first, we need to take a thorough physical examination of our bodies, and besides taking routine examinations, we need to do another four examinations.
The first item: do several more PCR tests, and nasal and throat secretions should be dipped enough to check whether the result shows positive. If it shows positive, it means there is still some active novel coronavirus in the body.
The second item: perform a neurological examination. Because neurological symptoms are highly prevalent in patients with long-term COVID, neurological testing is recommended in all patients with long-term COVID. Even if some patients communicate with their physicians, they do not have neurologically uncomfortable feedback. Many patients will report "brain fog", "difficulty concentrating" and "poor memory." Physicians should carefully evaluate the patient 's main symptoms on a case-by-case basis to design a patient' s neurological examination to determine pathophysiology.
If the patient is wealthy, or the physician has suspicious factors in the diagnosis, further in-depth examination is required. Following unconventional deeper neurological tests can be performed. For example, to rule out testicular brain injury, physicians are advised to perform functional magnetic resonance imaging MRI of the brain, including functional magnetic resonance imaging MR angiography of the brain. In elderly patients, imaging findings of early abnormal brain changes in Parkinson 's disease, Alzheimer' s disease, or other types of neurodegenerative dementia can be excluded by functional magnetic resonance imaging MRI of the brain. When patients report memory impairment, it is important to determine whether this memory impairment is caused by infection with COVID-19 or COVID-19 infection worsens pre-existing symptoms. If ischemic or hemorrhagic stroke is observed on functional magnetic resonance imaging MRI of the brain, we must consider medical therapy to prevent recurrent stroke.
Perfusion imaging (single photon emission computed tomography) may also be performed if the patient is wealthy or if the physician suspects the diagnosis. Cerebral perfusion imaging, which is perfusion imaging using CTP and MRP, has become a routine method to examine cerebral blood flow perfusion in stroke patients. Although there is still lack of some evidence that perfusion imaging is an essential test for stroke assessment, many centers have begun to use perfusion imaging to assess cerebral blood flow in patients. Cerebral perfusion testing may also show non-specific immunity triggers inflammation(innate immunity, which refers to the normal physiological defense function congenitally possessed by the body and can make the corresponding immune response to the invasion of various pathogenic microorganisms and foreign bodies. ), which is characterized by hypoperfusion in the prefrontal or temporal lobes. Although there is no established treatment for this problem, some drugs that improve brain blood may help improve the condition.
Further testing for Parkinson 's disease and Alzheimer' s disease should be performed if evidence of neurodegeneration is confirmed. For example, it is specifically tested whether the content of p-tau217 protein in blood greatly exceeds the standard of the average person. If it exceeds, it means it is in the early stages of Alzheimer's disease.
Third item: in addition to basic blood tests, we assessed thyroid hormones, zinc, ferritin, antinuclear antibodies, rheumatoid factor, and blood sedimentation rate in almost all patients. Patients with PASC may have electrolyte disturbances, anemia, thrombocytopenia, hypoalbuminemia, lipid abnormalities, and abnormal glucose metabolism. These data need to be combined with patient symptom descriptions to carefully analyze the pathogenesis behind reasoning to determine whether abnormal laboratory test results can explain the symptoms of PASC.
The fourth item: listen to the sounds of the heart and respiratory system with a stethoscope. Anemia, the signs of heart failure, latent arrhythmias such as atrial fibrillation, and pneumonitis from enteritis must be assessed when abnormal sounds are detected, or if breathlessness persists, and to check whether oxygen saturation decreases during exercise.
The following items, from item 5 to item 7, are required when the patient presents other symptoms.
Fifth item: rheumatoid arthritis or other related diseases must be analyzed when patients have symptoms of joint discomfort.
Sixth item: when the patient complains hair loss, we examine the scalp, return to the history of hair loss symptoms, and confirm the weekly amount of hair loss.
Seventh item: neuropsychological tests should also be performed if the patient has significant psychological problems.
Then, the results of the above comprehensive physical examination and four special examinations should be handed over to the doctor, and then the person should communicate with the doctor to describe one’s own long-term COVID symptoms of parkinsonism-like in detail.
Additionally, the doctor can design the best treatment for you. Because the situation varied from person to person, after the interview the treatment plan given by the doctor is also different, so this paper cannot give a general treatment plan.
The rough ideas for designing the treatment plan are as follows:
(1) According to the results of the patient's comprehensive physical examination and four special examinations as well as the communication with the patient, find out the most likely pathogenesis of the patient's long COVID symptoms of parkinsonism-like.
(2) Prescriptions are prescribed for treatment according to the pathogenesis and the patient 's physical condition. In most cases, the brain is found to be slightly inflamed, and at this time, treatments against neuroinflammation are usually used.
(3) For the main direction of medication, if novel coronavirus remains in the body, antiviral drugs such as Paxlovid should be used as a priority. If there is no virus in the body, the drug is used from the perspective of reducing or eliminating the chronic inflammation of the patient, improving the metabolic circulation and immune system of patients. For example, rintatolimod (immunomodulator) and coenzyme Q10 + NADH (mitochondrial modulator) can be used to improve the immune system of patients.
(4) If Parkinson 's disease and Alzheimer' s disease are diagnosed, Lecanemab is needed to control the development of the disease. Eisai and Biogen announced that Lecanemab, an Alzheimer 's disease (AD) drug jointly developed by the two sides, has achieved good results in clinical trials for the treatment of patients with mild Alzheimer' s disease and Alzheimer 's disease, resulting in mild cognitive impairment (MCI).
(5) Massage of the brain can also be tried, and studies have shown that this is also beneficial for recovery.
5.How to treat long-term COVID symptoms of parkinsonism-like from a traditional Chinese medicine(TCM) perspective?
From the theory of syndrome differentiation and treatment of TCM, the treatment of long-term COVID symptoms of parkinsonism-like can obtain more accurate TCM syndrome differentiation and more suitable TCM formulas from the following three steps.
(1) Perform the observation, smelling, hearing, and inquiring of traditional Chinese medicine diagnosis, and consult the comprehensive physical examination report and four special examination reports of western medicine in the previous section at the same time. Only in this way can TCM doctors obtain the most detailed disease information of patients to support them to make the most accurate syndrome differentiation and treatment of patients' conditions.
(2) TCM doctors will classify and summarize the main symptoms, accompanying secondary symptoms, physical condition, and sick parts of the internal organs of the patients according to the most comprehensive disease information of the patients. First, the main symptoms are the most unbearable symptoms of patients at present, such as Parkinsonism-like. Second, accompanying secondary symptoms are that suffered from the main symptoms, which means the patient is experiencing other uncomfortable symptoms, such as mental turbidity, chronic headache and so on. Third, to find out the physical condition of the patient, which means the patient's current physical health status, belongs to which category in the TCM constitution. For example, yang-deficiency constitution, phlegm-dampness constitution, qi-deficiency constitution, blood stasis constitution, etc.
(3) TCM doctors, according to the above summary, combined with the internal organs and meridians related to symptoms, comprehensively use the theory and practical experience of TCM to make TCM prescriptions for patients. If acupuncture and moxibustion are required, these programs will also be prescribed.
Traditional Chinese medicine (TCM) theory is mainly based on: Zhang Zhongjing’s “Treatise on Febrile Diseases”, “Synopsis of Golden Chamber”, Huang Yuanyu's “Four Sacred Hearts Source”, “Typhoid Fever Suspension”, “Jinkui Suspension”, “Changsha Yao Jie”, Li Dongyuan 's “Treatise on the Spleen & Stomach”, and Zhang Jingyue' s “Jingyue Quanshu”.
TCM Practical experience, which can be found in Google Scholar (Fig. https://scholar.google.com/), and search for keywords for TCM treatment of long-term novel coronavirus symptoms. For example， COVID-19 Traditional Chinese Medicine, Long Covid Traditional Chinese Medicine. A large number of academic papers on medical research on the treatment of Long Covid by traditional Chinese medicine can be found in this way.
In order to make it easier for everyone to understand the treatment process of TCM, the following is a TCM treatment case of a patient with long-term COVID-19 symptoms of parkinsonism-like.
Name: Qian, male, aged 54 years, height 167cm, weight 90 kg.
MEDICAL HISTORY:PCR was positive for novel coronavirus on 13 July 2021, followed by typical symptoms of novel coronavirus infection: fever, cough, sore throat, sputum with blood streaks, ageusia, and anosmia. Two weeks later, the symptoms of novel coronavirus infection gradually relieved and disappeared. Later, Parkinsonism-like symptoms appeared successively .
Physical examination report of western medicine: (1) PCR test for novel coronavirus showed positive results again.(2) PET (positron emission tomography, which can determine the occurrence and development of diseases by detecting the metabolic level of the human body) imaging analysis revealed decreased metabolic levels. (3) Proinflammatory markers were high and there was slight systemic chronic inflammation. (4) Immune system examination items revealed abnormal lymphocyte subset determination, C-reactive protein, and immunoglobulin data.
Main symptoms: parkinsonism-like symptoms, occasional gait freezing.
Accompanying secondary symptoms: occasional mental turbidity and cronic headache.
Prescriptions given by Western physicians:
(1) Paxlovid (paxlovid, antiviral drug, use to prevent the replication of novel coronavirus in vivo).
(2) Coenzyme Q10 + NADH (mitochondrial modulator).
(3) Rintatolimod (immunomodulator).
(4)Lecanemab, a new drug jointly developed by Eisai and Biogen, controls the development of the disease.
(5) Vitamin C, vitamin E, sulforaphane and resveratrol. (Use to reduce the inflammatory reaction in vivo.)
(6) Parkinson 's Walking Impairment Intelligent Crutches dedicated to patients with Parkinson' s gait freezing shall be used to assist walking and training.
TCM constitution: the body presents phlegm-dampness constitution.
TCM diagnosis evaluation: exogenous wind evil, Xifeng Tongluo, liver and kidney deficiency, slight lung and spleen deficiency, leading to parkinsonism-like symptoms.
Prescription given by the TCM doctor:
(1) Xifeng Tongluo Headache Tablets are used to clear away heat and toxic substances and reduce parkinsonism-like symptoms.
(2) Mailuotong capsule is used to dredge meridian vascular congestion.
(3) Buzhong Yiqi Tang is used to eliminate physical deficiency.
Acupuncture program given by the TCM: electricity is exerted to heat the moxibustion apparatus, and apply moxibustion at the following acupoints.
(1) Baihui, Ashi, Shenshu and Guanyuan points to improve brain metabolism.
6.Which kind of health products are beneficial to improving long-term COVID symptoms of early Parkinson 's disease?
Taking the patient above as an example, we give the following health product recommendations based on her condition:
(1) Omega 3 (Ω3) fatty acids, containing high amounts of DHA and EPA, are used to improve fatigue function and protect against cardiovascular and cerebrovascular diseases.
(2) VC,VD and VE are used to scavenge free radicals, anti-oxidation, and reduce systemic chronic inflammation.
(3) Curcumin is used to scavenge free radicals, anti-oxidation, activate NRF2, and reduce systemic chronic inflammation.
(4) Sulforaphane is used to scavenge free radicals, anti-oxidation, activate NRF2, and reduce systemic chronic inflammation.
(5) American ginseng is sliced for making tea or taken American ginseng capsules to replenish qi.
7.What exercises are beneficial to improving long COVID symptoms of parkinsonism-like?
Taking the patient above as an example, we give the following exercise advice based on his condition:
(1)Take gesture dance and finger exercises specifically designed for Parkinson's patients.
(2)Enjoy the wild of natural oxygen bars, such as walking in the deep forest, and perform deep breathing exercises.
(3)Assist with head massage.
8.What is beneficial to improving long COVID-19 symptoms of early Parkinson 's disease in terms of diet and sleep?
Taking the patient above as an example, we give the following diet and sleep advice based on his condition:
(1) Control carbohydrate intake, which means reducing the amount of staple food such as rice and noodle, and control animal fat intake.
(2) Do not take any food after lunch, and have breakfast and lunch only a day. Losing weight at least more than 10% of body weight, which means losing 9 kg, reducing the degree of obesity.
(3) Bubble bathing until slightly sweating before sleeping, and lie in bed to do general muscle tightness and relaxation training, improving sleep quality.
9.Patients with early Parkinson 's disease are welcome to contact with our Long Covid Care Center
If there are similar symptoms among readers, contact our Long Covid Care Center for assistance.
Phone: +852 5765 5768
Whatsapp: +852 5765 5768
【Disclaimer: The treatment of diseases is a very complex and professional affair. Due to the limitation, Long Covid Care Center can only carry out remote simple interviews, unable to face-to-face offline interviews and obtain comprehensive physical examination results. Therefore, the suggestions, guidance, protocols, and documents conveyed by our Long Covid Care Center to patients can only be used as a reference for patients to understand their diseases in many aspects, but cannot be directly used as a treatment plan. Patients must discuss their symptoms with doctors in local hospitals through face-to-face communication. After the patients completed the physical examination required by doctors, they would get a prescription issued by doctors and get the treatment under the guidance of doctors. Therefore, Long Covid Care Center hereby declares that our center is completely exempted from liability when any adverse consequences are caused by self-treatment of the patient for applying any contents convoyed by the center, that is, we do not bear any responsibilities.】