How can novel Coronavirus break through the first line of defence of the human body?

The COVID-19 epidemic is ravaging the world.
On 11 March, THE COVID-19 outbreak was declared a “global pandemic” by World Health Organization (WHO) Director-General Tedros Adhanom Ghebrev, raising the alert level to phase 6, the highest level.
Have studies suggest that without control measures, will be coronavirus (hereinafter referred to as: will be coronavirus) on the number of basic transmission (R0) (measuring virus infections, in the absence of the external force involvement, and people have no immunity, people infected with the disease to the average number of others) as high as 5.7, much higher than the SARS (severe acute respiratory syndrome (SARS) – CoV) during the epidemic of R0 value of 2.0 ~ 3.5.
Why is the novel Coronavirus infected population so large?
So efficient?
The route of transmission, the site of invasion, the binding site, the replication in vivo and so on, are all the questions that scientists are studying constantly.

Route of transmission

It is known that novel Coronavirus is mainly transmitted by respiratory droplets and close contact, and the infection source is mainly coVID-19 confirmed patients.
However, studies have proved that novel Coronavirus can be highly contagious at the end of incubation period of infection, and that mild infection, atypical infection and asymptomatic infected persons are all at risk of transmission.
When exposed to high concentration of aerosol for a long time in a relatively closed environment, there is the possibility of aerosol transmission.
Studies from two hospitals in Wuhan have shown that good ventilation can effectively reduce the risk of novel Coronavirus aerosol transmission.

The invasion of parts

Respiratory tract infection is to point to pathogen from the respiratory tract infection such as the nose of human body, pharynx, trachea and bronchus to invade and cause infective disease.

In general, the nasal cavity, trachea and bronchi, and alveolar macrophages work together to filter, remove and expel foreign bodies (Figure 1), which can effectively resist the invasion of pathogens such as viruses.
Once the pathogen breaks through these three barriers, it will first infect the mucous membrane of the upper respiratory tract, causing cough, runny nose and other mild symptoms.
If not controlled in time, the infection can spread to the lower respiratory tract, with more severe symptoms.
Novel Coronavirus is known to invade first the upper respiratory tract and then the trachea, bronchi, lungs and other organs of the lower respiratory tract.

Figure 1 Three barriers protecting the respiratory tract

Binding site

Existing studies have shown that novel coronavirus and SARS coronavirus are similar in that both novel coronavirus and SARS coronavirus invade cells through the combination of Spike protein on the virus surface and human ACE2, and replicate and multiply in cells.
In addition, novel Coronavirus’s spinoid can utilize the host cell protease to promote its affinity to the cell membrane and help it to enter cells with low ACE2 protein level (Figure 2).
Like a “master key”, unimpeded access to respiratory cells, break through the human body protection barrier.

Figure 2novel coronavirus invades the binding site of the cell

Virus replication

Once novel coronavirusRNA enters the human cell, it USES the cell to replicate in large Numbers, and constantly invades other cells.
When the virus replicates rapidly enough in an infected person, the body experiences clinical symptoms such as fever, dry cough, sore throat, loss of smell and taste, or headache and body pain.

Due to the openness of the lungs, viruses can easily enter the lungs through the respiratory tract, and the alveolus is rich in ACE2 receptor, so the lungs are the main battlefield of novel Coronavirus.
Pathological and anatomical studies found that patients with COVID-19 suffered severe lung injury, with a large amount of thick secretions overflowing from the alveoli, and virus was detected in the heart, liver, kidney, spleen, brain and other parts, while the concentration of virus in the lungs and pharynx was the highest.
Novel Coronavirus replicates extensively in lung tissue cells and is the direct cause of tissue and organ damage.

Mass virus replication may have another result.
Due to the overreaction of the immune system, immune cells attack indiscriminately, leading to more tissue damage and even multiple organ failure.
Pathological anatomic studies in Germany found that seven (58%) of the 12 patients who were dissected had developed deep vein thrombosis before death, and pulmonary embolism was the direct cause of death in four of them.
Novel Coronavirus infection may affect the blood clotting system and damage the lining of blood vessels, causing the formation of blood clots and thus pulmonary embolism.
The cytokine storm caused by the massive proliferation of the virus is also a possible cause of blood clot formation and vascular obstruction.

Novel Coronavirus can cause lung and other vital organs damage in many ways after novel coronavirus mass replication. Therefore, inhibiting viral replication at the initial infection site is very important.

The nose/pharynx is the initial site of novel Coronavirus infection

A study on the virological characteristics of patients published in Nature in early April 2020 indicated that a large number of novel Coronavirus were found in oropharynx/nasopharynx within 1 to 5 days after the onset of symptoms in patients diagnosed with COVID-19.
This is different from the known replication patterns of other coronavirus. The number of upper respiratory virus in SARS patients was the largest on the 7th day of the onset, while the number of upper respiratory virus in MERS patients was the largest on the 10th day of the onset. However, novel Coronavirus nasopharyngeal virus replicates more rapidly and in a larger quantity.
Through viral dynamics analysis (Figure 3), it was found that the oropharynx/nasopharynx virus replication in most patients was at the peak, but gradually declined after the onset of symptoms. Novel Coronavirus replication peak was before the onset of upper respiratory tract symptoms (i.e., asymptomatic infection stage).
The results suggest that asymptomatic, mild and atypical infected persons at the end of incubation period are contagious and may be at risk of transmission.

Figure 3 Novel Coronavirus kinetics, serum transformation and clinical observation

The dotted line represents the presumed trend of viral load in the front pharyngeal swab of symptom onset

Further study revealed that novel Coronavirus invaded the upper respiratory tract, but was active replication.
The virus USES the upper respiratory nose/pharynx as a “replication factory,” producing more and more new viruses.
The study published in Nature Medicine further confirmed that novel Coronavirus can infect the goblet cells of the nose. This cell has the ability of continuous secretion and its most important function is to secrete substances such as mucus.
With the help of this kind of cell power, novel Coronavirus can discharge more efficiently and infect more cells. The virus in mucous will spread through respiratory droplets, contact and other ways, and infect more people.

After the virus replicates rapidly in the incubation period and reaches a certain number, it will cause local cell damage and cause upper respiratory tract symptoms, such as running nose, sore throat, cough, etc. 81%novel Coronavirus infected patients can show the above mild symptoms.
A timely and effective antiviral intervention at this point will help prevent the fast-replicating virus from continuing down the trachea and bronchi to protect the lungs from attack.

Strengthen the body’s first line of defense against infection

From the above two studies, it can be known that novel Coronavirus started to invade the mucous membrane of nasopharynx and rapidly replicated in the upper respiratory tract. The virus can be discharged from the body through the respiratory tract and spread to infect others.
How to strengthen the first line of defence of human respiratory tract scientifically, suggest to start from the following three points:

First of all, the implementation of effective physical barrier, cut off the route of transmission.

A team from The Massachusetts Institute of Technology published a study in The Journal of The American Medical Association showing that droplets of The nasopharyngeal secretions carrying The virus can travel up to six metres in a cough and up to eight metres in a sneeze.
Novel Coronavirus makes it possible to widely spread, according to results published in Proceedings of the National Academy of Sciences that a microdroplet produced during speech can remain in a closed environment for 12 minutes.
A novel Coronavirus infected person enters a restaurant and, if left unprotected, spreads the virus across the restaurant in 30 minutes, according to a simulation study in Japan.
An article published by the US Centers for Disease Control and Prevention also suggested that an asymptomatic infected person went out to eat and nine people from three families at the restaurant became infected after eating.

From these studies, it is not difficult to find that only by keeping away from the source of infection and cutting off the transmission route, can the virus be effectively blocked.
In the absence of effective vaccines and specific drugs, we can also see from our successful anti-epidemic experience that through early detection, effective isolation of the source of infection, coupled with measures such as wearing masks and frequent hand washing to block the transmission routes, it is the most effective way to control the transmission of coronavirus and quickly control the epidemic situation.

Secondly, maintain a regular healthy life to enhance immunity and enhance the ability to fight against viral infections.

In the face of COVID-19, in addition to the above protective measures, strengthening individual resistance is a more effective prevention and treatment measures.
The nutritional status of the body is closely related to the immune function and affects each other.
Therefore, to maintain a good diet, pay attention to reasonable dietary collocation, appropriate increase in quality protein, contribute to the body to enhance the ability to fight against viral infection.

Exercise is closely related to the immune function of the body. Regular and appropriate exercise can enhance the immune ability of the human body and enhance the resistance to infectious diseases.
Exercise is closely related to the immune function of the body. Proper exercise can stimulate the immune system and help improve the resistance to novel Coronavirus.
In addition, adequate and quality sleep can improve the body’s immunity. On the contrary, insufficient or poor sleep can lead to a decline in the body’s immunity and provide an opportunity for virus infection.
Therefore, paying attention to the combination of work and rest helps to improve the body’s immunity.
Maintaining a regular and healthy pace of life can help improve the body’s immunity and enhance its ability to fight off viral infections.

Third, appropriate early intervention for high-risk and vulnerable groups may bring benefits.

A study in Clinical Infectious Diseases found that novel Coronavirus can achieve immune escape by highly glycosylation, inhibit the secretion of antiviral cytokines such as interferon, and enable the virus to evade immune surveillance and response in the early stage of invasion, making the human body more vulnerable to virus infection.
The study results suggested that for high-risk and susceptible people infected with novel Coronavirus, supplementing exogenous interferon in the nasopharynx after virus exposure can directly inhibit virus replication, and at the same time, the virus can be removed as soon as possible by improving the innate immunity of human body.

A in hubei during the disease resistance of interferon alpha nasal drug prevention will be coronavirus infection studies [12], according to the results of 2944 healthy medical personnel to accept for four weeks of interferon alpha nasal prophylactic medication, whether it’s high-risk groups (direct contact with patients with confirmed) or low risk population (not direct contact with patients with confirmed), are not happen personnel will be coronavirus infection.

China has accumulated rich experience in the use of interferon in the treatment of children with bronchiolitis, viral pneumonia, acute upper respiratory tract infection, hand foot and mouth disease, SARS and other viral infectious diseases, and formed the corresponding expert consensus.
Early use of interferon can help reduce symptoms and shorten the course of the disease.
In the first and second editions of China’s “Children novel Coronavirus infection Diagnosis, treatment and prevention expert consensus”, interferon spray and interferon atomization can be used for antiviral treatment of children novel Coronavirus infection.
To protect vulnerable populations, those at high risk of exposure to a suspected novel Coronavirus infection can also be prevented with topical interferon sprays.

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