Immune System Health

Cytokines Storm Vs. COVID-19

The content has not been evaluated by the Food and Drug Administration (FDA). It is for educational purpose only. It is not intended to diagnose any disease or condition, or to recommend a treatment for any disease or condition.

Coronavirus 2019 disease is a respiratory infectious disease, it was first reported on December 31, 2019 in Wuhan, Hubei Province. WHO officially named Coronavirus 2019 disease as COVID-19.

As of March 4th, 2020, there are more than 94,000 confirmed coronavirus cases worldwide. COVID-19 has killed more than 3,100 people globally. Although the majority cases are in mainland China, but a significant jump cases in Italy, Germany, Iran, South Korea and many other countries in the world. Among those people who get affected or died, 80% of them are 60 years old or older. 75% of them have pre-existing health conditions including cardiovascular disease and diabetics, etc.

2019 novel coronavirus (2019-nCoV) is a new coronavirus belonging to the genus β. On February 11, 2020, the International Committee on Taxonomy of Viruses (ICTV) named the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 and asymptomatic infection can transmit 2019-nCoV. Respiratory droplet transmission is the main route of transmission and can also be transmitted through contact. There is also the risk of aerosol transmission in confined enclosed spaces. COVID-19 patients can detect 2019-nCoV in stool, urine, and blood; some patients can still test positive for fecal pathogenic nucleic acid after the pathogenic nucleic acid test of respiratory specimens is negative. The crowd is generally susceptible. Children, infants, and young children also develop disease, but the condition is relatively mild.

Clinical Characteristics
The incubation period is 1 to 14 days, mostly 3 to 7 days, with an average of 6.4 days. Main symptoms are fever, fatigue, and dry cough. May be accompanied by runny nose, sore throat, chest tightness, vomiting and diarrhea. Some patients have mild symptoms, and a few patients have no symptoms or pneumonia.

The elderly and those suffering from basic diseases such as diabetes, hypertension, coronary atherosclerotic heart disease, and extreme obesity tend to develop severe illness after infection. Some patients develop symptoms such as dyspnea within 1 week after the onset of the disease. In severe cases, they can progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. The time to progression to severe illness was approximately 8.5 days. It is worth noting that in the course of severe and critically ill patients, there may be moderate to low fever, even without obvious fever. Most patients have a good prognosis, and deaths are more common in the elderly and those with chronic underlying disease.

The early CT examination showed multiple small patches or ground glass shadows, and the internal texture of the CT scans was thickened in the form of grid cables, which was obvious in the outer lung zone. A few days later, the lesions increased and the scope expanded, showing extensive lungs, multiple ground glass shadows, or infiltrating lesions, some of which showed consolidation of the lungs, often with bronchial inflation signs, and pleural effusions were rare. A small number of patients progressed rapidly, with imaging changes reaching a peak on days 7 to 10 of the course. Typical “white lung” performance is rare. After entering the recovery period, the lesions are reduced, the scope is narrowed, the exudative lesions are absorbed, part of the fiber cable shadow appears, and some patients’ lesions can be completely absorbed.

In the early stage of the disease, the total number of white blood cells in the peripheral blood was normal or decreased, and the lymphocyte count was reduced. Some patients may have abnormal liver function, and the levels of lactate dehydrogenase, muscle enzyme, and myoglobin may increase; troponin levels may be increased. Most patients had elevated CRP and ESR levels and normal procalcitonin levels. In severe cases, D-dimer levels are elevated, other coagulation indicators are abnormal, lactic acid levels are elevated, peripheral blood lymphocytes and CD4 + T lymphocytes are progressively reduced, and electrolyte disorders and acid-base imbalances are caused by metabolic alkalosis See more. Elevated levels of inflammatory cytokines (such as IL-6, IL-8, etc.) may occur during the disease progression stage.

Treatment Plans
A. Antiviral treatment
You can try hydroxychloroquine sulfate or chloroquine phosphate, or Abidol for oral administration, interferon nebulization and inhalation, interferon κ is preferred, and interferon α recommended by the national scheme can also be applied. It is not recommended to use 3 or more antivirals at the same time. The viral nucleic acid should be stopped in time after it becomes negative. The efficacy of all antiviral drugs remains to be evaluated in further clinical studies.

For patients with severe and critical viral nucleic acid positives, recovery patients can be tested for recovery plasma. For detailed operation and management of adverse reactions, please refer to the “Clinical Treatment Program for Recovery of New Coronary Pneumonia Patients During Recovery Period” (trial version 1). Infusion within 14 days of the onset may be more effective. If the viral nucleic acid is continuously detected at the later stage of the disease, the recovery period of plasma treatment can also be tried.

B. Treatment of mild and ordinary patients
Supportive treatment needs to be strengthened to ensure sufficient heat; pay attention to water and electrolyte balance to maintain internal environment stability; closely monitor patient vital signs and finger oxygen saturation. Give effective oxygen therapy in time. Antibacterials and glucocorticoids are not used in principle. The patient’s condition needs to be closely monitored. If the disease progresses significantly and there is a risk of turning into severe, it is recommended to take comprehensive measures to prevent the disease from progressing to severe. Low-dose short-course glucocorticoids can be used with caution (see the application section of glucocorticoids for specific protocols). Heparin anticoagulation and high-dose vitamin C are recommended. Low-molecular-weight heparin 1 to 2 per day, continued until the patient’s D-dimer level returned to normal. Once fibrinogen degradation product (FDP) ≥10 µg / mL and / or D-dimer ≥5 μg / mL, switch to unfractionated heparin. Vitamin C is administered at a dose of 50 to 100 mg / kg per day, and the continuous use time is aimed at a significant improvement in the oxygenation index. If lung lesions progress, it is recommended to apply a large-dose broad-spectrum protease inhibitor, ulinastatin, at 600 to 1 million units / day until the pulmonary imaging examination improves. In the event of a “cytokine storm”, intermittent short veno-venuous hemofiltration (ISVVH) is recommended.

C. Organ function supportive treatment for severe and critically ill patients
1. Protection and maintenance of circulatory function: implement the principle of early and actively controlled fluid replacement. It is recommended to evaluate the effective volume and initiate fluid therapy as soon as possible after admission. Severe patients can choose intravenous or transcolonic fluid resuscitation depending on the conditions. The preferred supplement is lactated Ringer’s solution. Regarding vasoactive drugs, noradrenaline and dopamine are recommended to maintain vascular tone and increase cardiac output. For patients with shock, norepinephrine is the first choice. It is recommended to start low-dose vasoactive drugs at the same time as fluid resuscitation to maintain circulation stability and avoid excessive fluid infusion. Cardioprotective drugs are recommended for severe and critically ill patients, and sedative drugs that inhibit the heart are avoided as much as possible. For patients with sinus bradycardia, isoprenaline can be used. For patients with sinus rhythm, a heart rate of <50 beats / min and hemodynamic instability, intravenous pumping of small doses of isoproterenol or dopamine to maintain the heart rate at about 80 beats / min.

2. Reduce pulmonary interstitial inflammation: 2019-nCoV leads to severe pulmonary interstitial lesions that can cause pulmonary function deterioration. It is recommended to use a large dose of a broad-spectrum protease inhibitor ulinastatin.

3. Protection of renal function: Reasonable anticoagulant therapy and appropriate fluid therapy are recommended as soon as possible. See  “Cytokine storm” for prevention, protection and maintenance of circulatory function.

4. Protection of intestinal function: Prebiotics can be used to improve the intestinal microecology of patients. Use raw rhubarb (15-20 g plus 150 ml warm boiling water) or Dachengqi decoction for oral administration or enema.

5. Nutritional support: parenteral nutrition is preferred, via nasal feeding or via jejunum. The whole protein nutrient preparation is preferred, and the energy is 25 to 35 kcal / kg (1 kcal = 4.184 kJ) per day.

6. Prevention and treatment of cytokine storm: It is recommended to use large doses of vitamin C and unfractionated heparin. Large doses of vitamin C are injected intravenously at a dose of 100 to 200 mg / kg per day. The duration of continuous use is to significantly improve the oxygenation index. It is recommended to use large doses. Dose of the broad-spectrum protease inhibitor ulinastatin, given 1.6 million units, once every 8 h, under mechanical ventilation, when the oxygenation index> 300 mmHg can be reduced to 1 million units / d. Anticoagulation can be taken The treatment protects endothelial cells and reduces the release of cytokines. When FDP ≥ 10 µg / mL and / or D-dimer ≥ 5 μg / mL, anticoagulation is given to unfractionated heparin (3 to 15 IU / kg per hour). Heparin is used for the first time. The patient’s coagulation function and platelets must be re-examined 4 h later. ISVVH is used for 6 to 10 h every day.

7. Sedation and artificial hibernation: Patients undergoing mechanical ventilation or receiving ECMO need to be sedated on the basis of analgesia. For patients with severe man-machine confrontation during the establishment of an artificial airway, short-term application of low-dose muscle relaxants is recommended. Hibernation therapy is recommended for severe patients with oxygenation index <200 mmHg. Artificial hibernation therapy can reduce the body’s metabolism and oxygen consumption, and at the same time dilate the pulmonary blood vessels to significantly improve oxygenation. It is recommended to use continuous intravenous bolus medication, and the patient’s blood pressure should be closely monitored. Use opioids and dexmedetomidine with caution. Because severely ill patients often have elevated IL-6 levels, which can easily lead to bloating, opioids should be avoided; 2019-nCoV can still inhibit sinus node function and cause sinus bradycardia, so it should be used with caution on the heart. Inhibitory sedatives. In order to prevent the occurrence and exacerbation of lung infections, and to avoid prolonged excessive sedation, try to withdraw muscle relaxants as soon as possible. It is recommended to monitor the depth of sedation closely.

8. Oxygen therapy and respiratory support: ① nasal cannula or mask oxygen therapy, SaO2 ≤93% under resting air condition, or SaO2 <90% after activity, or oxygenation index (PaO2 / FiO2) 200-300 mmHg with or without respiratory distress; continuous oxygen therapy is recommended. ② High-flow nasal cannula oxygen therapy (HFNC), receiving nasal cannula or mask oxygen therapy for 1-2 hours, oxygenation fails to meet treatment requirements, and respiratory distress does not improve; or hypoxemia during treatment and / or exacerbation of respiratory distress; or an oxygenation index of 150 to 200 mmHg; HFNC is recommended. ③ Noninvasive positive pressure ventilation (NPPV), receiving 1 to 2 h of HFNC oxygenation does not achieve the treatment effect, and there is no improvement in respiratory distress; or hypoxemia and / or exacerbation of respiratory distress during treatment; or When the oxygenation index is 150 ~ 200 mmHg; NPPV can be selected. ④ Invasive mechanical ventilation, HFNC or NPPV treatment does not meet the treatment requirements for 1 to 2 hours of oxygenation, and there is no improvement in respiratory distress; or hypoxemia and / or exacerbation of respiratory distress during treatment; mmHg; invasive ventilation should be considered. Protective ventilation strategies with a small tidal volume (4-8 mL / kg ideal body mass) as the core are preferred.

9. Implementation of ECMO: Those who meet one of the following conditions may consider implementing ECMO. ① PaO2 / FiO2 <50 mmHg for more than 1 h; ② PaO2 / FiO2 <80 mmHg for more than 2 h; ③ Arterial blood pH <7.25 with PaCO2> 60 mmHg for more than 6 h. ECMO mode is preferred for intravenous-venous ECMO.

COVID-19 Transmission
Patients with COVID-19 and asymptomatic infection can transmit 2019-nCoV. Respiratory droplet transmission is the main route of transmission and can also be transmitted through contact. There is also the risk of aerosol transmission in confined enclosed spaces. COVID-19 patients can detect 2019-nCoV in stool, urine, and blood; some patients can still test positive for fecal pathogenic nucleic acid after the pathogenic nucleic acid test of respiratory specimens is negative. The crowd is generally susceptible. Children, infants, and young children also develop disease, but the condition is relatively mild.

Strategy to Combat COVID-19
At the moment, there is no vaccinations for COVID-19. So prevention is the key. Prevent the virus from coming into your body defense system. Try your best to stop cytokines storm from happening.

What is Cytokines Storm

Cytokines are small proteins that act as chemical messengers for communication between cells. Almost every cell in the body is capable of secreting cytokines, the many families of which are made up of proteins, peptides, or glycoproteins. Each family is produced for a specific function and matches a receptor on the surface of its target cell type. The functions of these proteins include regulating immune responses or inflammation and stimulating blood cell production. Cytokines have both local and systemic effects and may act on the same cell from which they were released, or other nearby cells.

I. Before the Virus Enters the Body

1. Chemokines and Interferons
Chemokines, one type of cytokine, send messages to other cells through a process called chemotaxis. The messengers initiate the immune response by alerting other cells of threats and guiding them to the site of injury or infection. Interferons are proteins secreted in response to bacteria, viruses, parasites, or cancer cells. They inhibit virus replication by immediately signaling nearby cells to shield themselves from the virus and activating natural killer T-cells to destroy infected cells.

2. Tumor Necrosis Factor
Tumor necrosis factor, or TNF, are cytokines that act on abnormal cells and attack cancer cell lines. They produce rapidly in response to infection by gram-negative bacteria and may cause fever and inflammation lasting up to 24 hours. TNF activates the liver to produce proteins the body needs for systemic immune responses to severe or widespread infection.

3. Interleukins, Lymphocytes, Monokines
Interleukins are a large and varied category of cytokines produced by leukocytes, especially T-cells. Their function depends on the type of white blood cell with which they interact. Lymphocytes coordinate the immune response through communication with other cells. Monokines come from monocytes or macrophages and fulfill many of the same functions as lymphocytes. Cytokines secreted by T-cells and macrophages coordinate the entire network of interacting cells during an immune response.

4. Erythropoietin
Erythropoietin or hemopoietin is a cytokine secreted by the kidneys to trigger red blood cell production in bone marrow. A constant supply of erythropoietin is secreted to compensate for normal turnover of red blood cells. Red blood cells carry oxygen, so when oxygen levels are too low, the body tries to correct this by stimulating the production of additional blood cells. Colony-stimulating factors, or CSFs, are another type of cytokine necessary for differentiation of blood cells from stem cells in the bone marrow.

II. After the Virus Enters the Body
1. Acute Inflammation
They cause acute inflammation as part of the healing process by pulling leukocytes, such as neutrophils, monocytes, and macrophages, from circulating blood. The body also activates other leukocytes known as mast cells at the site of infection or injury. Interactions between cytokines and leukocytes cause nearby blood vessels to widen and become porous so additional white blood cells and blood components can reach the site quickly.

2. Initiating an Immune Response
T-helper cells identify pathogens or foreign substances in the body then release cytokines into the bloodstream. As they travel through, they trigger other cells to mount an immune response and activate T- and B-cells. Activated macrophages surround and break down foreign material, engulf and kill microorganisms, and remove dead cells. This is the start of the cascade induction that results in many cytokine cells being released from multiple cell types; a continuous feedback loop escalates an immune response until the compounds can eliminate the threat.

3. Chronic Inflammation
Anti-inflammatory cytokines regulate inflammation. For example, some interleukins prompt inflammation while other types reduce inflammation to maintain balance during an immune response. Arthritis, joint disease, and chronic pain can result from excessive cytokine production, unbalanced cytokines, or erroneous production without a pathogen or injury to target. Excessive pro-inflammatory cytokines correlate with osteoarthritis, while anti-inflammatory cytokines, especially TNF, that damage tissue appear to be a cause of rheumatoid arthritis.

4. Cytokine Interaction (Cytokine Storm)
Cytokine interaction with cells and each other is complex. Pleiotropism refers to different effects from the same cytokine, depending on the target cell type. Redundancy occurs when multiple cytokines have the same effect, while synergism means the combined effects are greater than either one individually. Antagonism is the action of one cytokine inhibiting other cytokines. They locate and attach to designated cell receptors quickly and function for a short time, so new cytokines can be released as the immune response adapts to changing circumstances.

Balanced Cytokines and Improve Immunity
A healthy, nutrition-rich diet is essential to maintaining a proper balance of cytokines. Lack of sleep, nutritional deficiencies, and a sedentary lifestyle contribute to poorly balanced cytokine production, which could compromise the immune system. Acute stress over a short time lowers production of inflammatory cytokines while increasing anti-inflammatory cytokines, but chronic stress results in higher levels of pro-inflammatory cytokines. Chronic stress is a risk factor for many negative health conditions including inflammatory disease, depression, and fatigue.

More detail about Functional Nutrition Intervention for COVID-19

from FX Strategies Part II ( Coming Soon)

Summary

Coronavirus 2019 disease is a respiratory infectious disease. It started from Wuhan, China in December, 2019 and has spread across many countries in the world.  As of March 4th, 2020, there are more than 94,000 confirmed coronavirus cases worldwide and over 3,100 people died globally.

Although the majority cases are in mainland China, but a significant jump cases in Italy, Germany, Iran, South Korea and many other countries in the world. Among those people who get affected or died, 80% of them are 60 years old or older. 75% of them have pre-existing health conditions including cardiovascular disease and diabetics, etc.

At the moment, there is no vaccine available, affected patients try to cooperate with doctors to do the treatment. People who have a strong immunity without pre-exiting diseases may survive.

Coronvirus will not disappear soon. It will live with our daily life. Coronavirus is full of uncertainty. It has a significant incubation period. Most people have 7-14 days while some people can have 28 days before the symptoms occur. Doctors can not do much to help people who only have some symptoms but not confirmed as a COVID-19 case.

Before the virus enters the human body, everybody has an “equal opportunity” to get it. The virus collaborates across the societies and travel through your community, your neighbor and your city, your country and all over the world.  

Therefore,  prevention will be the best way to help yourself and your loved ones go through this challenge time. Don’t be panic!  Improve immune system, don’t let cytokines storm happen in the first place. Have balanced diets with some lifestyle modification.  Be confident!  We will win the battle!

Prevention! Prevention! Prevention!

Preventing pathogens from entering the body is the best defense and treatment. After the virus enters the body, it is an invisible war in the body. It all depends upon your natural autoimmunity.

Learn How to Use Functional Nutrition Intervention for COVID-19

Functional Nutrition Intervention Strategy Part II (Coming Soon)

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Acknowledgements

On March 1st, the Chinese Journal of Infectious Diseases, which was hosted by the Shanghai Medical Association, pre-published the “Expert Consensus on Comprehensive Treatment of Coronavirus in Shanghai 2019” (http://rs.yiigle.com/m/yufabiao/1183266.htm), which has attracted widespread attention in the industry. Shanghai TV also reported on the news last night. This consensus was reached by 30 experts representing the strongest medical force for the treatment of new-type coronavirus pneumonia in Shanghai. Through the study and summary of more than 300 clinical patients, and fully learning from the treatment experience of colleagues at home and abroad, the “Shanghai Treatment Plan” was formed. At the end of the article, the list of 30 subject experts (18 writing experts and 12 consulting experts) from various medical institutions in Shanghai is attached.

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Wei Wei Ning

I am Wei Wei Ning, an author and a blogger of https://lifestylemedicine4u.com.

I am a Certified Transition Lifestyle Coach, Holistic Functional Nutrition Counselor, Digital Entreprenuer and Digital Health & Lifestyle Educator.

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