Why the novel coronavirus is able to inflect great pain and misfortune on human? One of the reasons is that we keep on thinking the CIVID-19 pandemic in traditional ways, overlooking the fact that “Coronavirus can reside and function in the nasal cavity & throat area, and nose & throat are located ahead of the blood circulation and lymphoid systems." Therefore, we not only have hard time to understand the etiology and pathology of COVID-19, but also do not know how to deal with the pandemic effectively.
Generally, invaded pathogens flow along with the blood stream and reach target cells, in which they reside and multiply. In so doing, they encounter the innate immunity and also induce the production of antibody against them. Thereafter, the immune members look for pathogens and kill them. However, in the case of coronavirus infection, although invaded viruses also invoke immune response and induce production of antibody, they can stay and grow in the nasal cavity & throat area without contacting the blood initially. Indeed, initially only a few viruses are able to reach the bronchi and alveoli, at which they contact the blood and trigger the immune response. In other word, before contacting the blood and inducing antibody production, coronaviruses can function and abuse their power in nose & throat; and even in the presence of antibody, coronavirus still can continue to live, grow, and discharge in/from nose & throat.
No doubt, the existence and continuation of a pathogen depend on two things, being able to live and spread. Nose & throat provide coronaviruses such a heaven, with cells for virus to hide and grow, and with facilities for virus to discharge and spread.
One single virus is not sufficient to induce full immune response. During the accumulation and incubation period in the nose & throat area, viruses can be discharged from the patient and infect others. Since the patient has no clear symptom at this time, he could be asymptomatic and infectious.
After infection, the cell membrane permeability of alveoli increases and body fluid flows into the air sacs. Due to constant breathing, the fluid dries up quickly and becomes vicious. Such thick material decreases the oxygen intake of alveoli on one hand, and prevents the capturing and killing of viruses by immune members on the other hand. In a way, viruses can buried itself in the thick pasta of body fluid and dead cell ruin to avoid the immunity attack. This could be one of the reasons that some asymptomatic patients are infectious, and some patients are infectious again after recovery.
Since the lung of COVID-19 patient is infiltrated with fluid, application of ventilator should be careful. High pressure could push the fluid into deeper positions; high pumping frequency could dry up the fluid too fast and cause problem. As we know, dehydration stops all reactions, such as snot hardens to form booger. Clearly, if the liquid in the air sacs of alveoli hardens too fast, it is dangerous. For the similar consideration, the medical staff should pay attention to the dietary treatment to patients, so as to help them in easing off thick mucus formation.
Although coronavirus dies easily, it can defeat the host with quantity superiority. In general, every man has his basic strength of immunity in resistance to some degree of virus invasion. If the invasion quantity is too much to handle, higher level of immunity mechanisms such as antibody production and neutralization, inflammation, fever and so on will kick in. During the battle, the friendly fires of the immunity could also damage human tissues and organs severely.
The fierce fight between virus and human is a “war of quantity. " Who is going to win depends on whether “the duplication rate of virus" can overran “the supply of immunity power." Overall, if the basic strength of immunity is too weak to begin with, the patient is old, ill, or has many injuries, the virus might win. In this condition, life support machines and special drug treatments are required to help the immunity to fight on.
How does the virus surge in quantity? Let us use “flyer verses copy machine" as an example. The wind blows up “a flyer" which accidently drops into “a copy machine" and turns on the printing mechanism, resulting production of numerous flyers. Soon the machine runs out of paper, ink, and power. The flyers then are looking for other copy machines to make copies. In similar to such reproduction cycling, viruses can quickly surge to a quantity that can overwhelm the immunity of the host.
How important is the antibody? First, having the virus induced antibody is like having a vaccination in the most powerful and nature way. Polyclonal antibodies alone can neutralizing viruses quickly and quietly without generating cytokine storm. As far as antibodies can reach, viruses will be destroyed and the tissues and organs are under protection, excepting those hiding in the nose & throat area and those inside particular cell bodies. However, since antibodies are circulating, the free and hiding amount of virus will be low, and the sneezing and coughing activities will be low, the patient will have no or little infectious power. Second, antibody positive means the patient has been infected; this information shows the spread and severity of the pandemic, and can be used to decide when people can go back to school or work. If two third of the population are antibody positive, the virus will be difficult to spread among this group of people, or at least it will not collapse the medical system if it does spread. Therefore, developing a simple, quick, inexpensive and automated antibody detection for massive testing is urgent and important.
Why some patients are asymptomatic? If a group of people were each given 50 spankings. Some may not make it, some may recover the next day and do business as usual. In other word, some will have symptom others will not. Also, if the invasion of virus is in the nose & throat area only, the patient may have running nose without coughing, in similar to having a common cold. Moreover, the severity of the symptom depends on the quantity of virus load and whether the target cell membrane has receptor for virus to bind and internalize.
How to find out the asymptomatic patient? Sooner or later the infected patient will produce antibody against the virus.; therefore, “antibody positive"(patient with antibody) = symptomatic + asymptomatic. After antibody testing, we can identify the positive patients and realize the distribution of asymptomatic patients. All antibody positive patients should be under control, be isolated or treated if required, and tested for virus nucleic acid analysis. If two weeks later they can pass both the nucleic acid and antibody tests, they can be released.
Does negative antibody test result indicate the patient has not been infected? Not necessarily true. The patient could be infected recently but the antibody level is too low to be detected. To be safe and sure, this person needs a nucleic acid test, and also another antibody test two weeks later. Overall, antibody test, nucleic acid test, biomarker tests, clinical examination, and medical history should all be put together for making a good diagnosis.
Are diagnostic tests on the market today reliable? Diagnostic tests are not 100% accurate, and all are with certain limitations. The test results can be useful when in combination with other test results and medical examinations. “Nucleic acid test kit" detects markers of virus nucleic acid; theoretically the specificity is high. However, since it is a physical detection, the meaning of the test result is vague. For example, either whole virus or fragments of virus shows positive result; samples obtained from infected patient, or from a person who just sucks in a small amount of virus which can be sneezed off or coughed off entirely easily, will show positive results; there is no sure sampling method. Also, sampling and testing require professional skill (Warning: Improper nasal swapping could damage the brain, particularly the pituitary gland.) and are expensive, it is difficult to perform rapid and massive nucleic acid testing. On the other hand, “Antibody rapid test kit" detects the serological antibody, its sampling and testing are easy, simple, inexpensive, and require no instrument; it is suitable for on-site testing. However, because the compounds fixed on the solid phase “for the antibody capturing" usually are recombinant proteins, the test sensitivity and accuracy are not high. If the capturing compound is “synthetic peptides", the false positive result will be minimum, but then it may require longer incubation time to increase the test sensitivity. Overall, all tests available today have not been subjected to extensive clinical trials, it will take time to improve and mature.
How important is it wearing the face mask? Mask is very effective in trapping droplet and aerosol. Assuming a patient can infect a normal person 6 feet away in a minute. Now if this patient wears a mask, more than 99% of the viruses in his exhalation will be blocked by the mask, and the spreading force and distance toward the victim will also be much less. If the victim also wears a mask, more than 90% of the viruses in wet droplets cannot penetrate his mask. Altogether, the chance of the victim in becoming infected decreases to less than 0.1%. A study made by The New York Times shows that the prevalent rate of COVID-19 in African American and Spanish American is almost twice of that of Chinese American in New York city. Obviously, the protection is enormous for the whole national.
Why the COVID-19 is less prevalent in Taiwan? Most people in Taiwan wear masks in public areas daily. Also, many of them may have antibodies due to previous infections and immunizations, which could cross-react with coronavirus. This is not surprising, because Taiwan has good public medical services and also a unique geological position.
Why coronavirus is so difficult to deal with? Due to constant breathing, the respiratory system has lower temperature than other vital organs, that makes the respiratory system a desirable place for the virus to survive and spread. Studies show that coronavirus can invade many tissue cells and immune cells, resulting in the decrease of lymphocyte, that is contrary to typical viral infections. When the immune cells are attacked, the weakening immune system could in turn flare up bacterial infections, in similar to AIDS virus infection. Moreover, if the patient had been infected by a pathogen weaker than coronavirus and then infected by coronavirus next, the immune response may abandon the quiet and efficient pathway of neutralizing viruses with polyclonal antibodies, instead it may take the violent and stormy pathway of binding viruses with monoclonal antibodies and knock down the patient quickly. This is called the antibody dependent enhancement (ADE) effect, which often jeopardizes young patients by surprise.
Who is safe to goes back to work? At present the sensitivity, accuracy, and reliability of all diagnostic tests have room for improvements, medical conclusion is not easy to make. However, certain rationales can help in making judgments:
- Everyone should take both nucleic acid and antibody tests initially, and take both tests again 14 days later.
- Patients with symptom and/or patients with positive nucleic acid result should be isolated and treated.
- Patients with negative results in nucleic acid and antibody after 14 days quarantine can go back to work.
- After 14 days quarantine, patients with negative result in nucleic acid and positive result in antibody are also safe to work.
What could be the outcome of the pandemic? At the diagnostic level, high throughput machine may process millions of droplet size samples daily, in detections of viral nucleic acid or antibody. At the government level, big data may provide information of the scope, spread, and change of the pandemic, which will facilitate the preparation and distribution of medical resources. The rolling big data may also help in deciding when to restart schooling and working, so as to bring back the economy and normal life. At the personal level, each person may have an ID or passport with coronavirus related data, including every testing, medical examination, prognosis, and travel history. Other medical related data can be added later on.
What goes to the extreme will turn to the opposite. Human beings have roamed free at will for a long time. Now the naive coronavirus is blocking the way and delivers a message “Business as usual no more!"
Written by John F. Chiu in Los Angeles on April 19, 2020
PhD in Biochemistry, retired research scientist
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