The COVID-19 pandemic has ravaged the world.
For this new virus, "cunning" is the first impression of many people on it:
The incubation period is infectious, and the asymptomatic patients are also infectious, and the clinical symptoms are atypical;
The transmission force is stronger than SARS, but the fatality rate is not too high;
The incubation period is not fixed, the onset of infection can occur within 1 day, and it can also be "hidden" in the body for up to 24 days;
In addition to "traditional" respiratory droplets, indirect contact with the mucous membranes of the eyes, mouth or nose, there may also be aerosols, fecal-oral transmission and other possibilities...
Highly contagious, fast-spreading, insidious disease, low fatality, atypical symptoms...
All this is to make themselves reproduce faster and spread better, which is the instinct of all living things to survive and reproduce.
As of now, scientists from all over the world have not dared to have a relatively thorough understanding of the new coronavirus named SARS-CoV-2 by the World Health Organization. However, just as the so-called "know oneself and know the other, never lose a battle", only by fully understanding the enemy can we find a way to defeat it! We combed through the existing information in hopes of uncovering a corner of its weird veil.
Why is the novel coronavirus cunning?
This has to start with the structure and characteristics of the new coronavirus.
The novel coronavirus, as the name suggests, is a type of coronavirus. This is a class of RNA viruses, spherical or oval in shape, and the virus has a "coat" made of protein on the outside, which is called "capsule membrane" by medicine;
There are many prominent "nails" on the membrane, called "spinous protrusions", which are shaped like "crowns" under electron microscopes, which is where the name "coronary" modevirus comes from.
Image source: Network
When the new coronavirus infects the human body, after entering the human throat through the nasal cavity, mouth and eye mucosa, it can further spread to the trachea and thinner bronchi, and then reach the alveoli.
However, at every step into the alveoli, the virus is defended and monitored by immune cells. Sneezing, coughing, and coughing up sputum are all manifestations of immune cells "fighting" the virus.
Feature 1: The key opens the door, and the door is deep in the human body, resulting in a high false negative rate of nucleic acid testing
The "nails" on the capsule membrane of the new coronavirus are mainly composed of a protein called "spike glycoprotein", which is the key to the infectivity and pathogenicity of the new coronavirus.
Spinous processes, made up of spike glycoproteins, can recognize and bind to a receptor on the surface of human cells, angiotensin-converting enzyme 2 (ACE2)[1], like a "key" opening a "door".
Structure under electron microscopy of the new coronavirus Features Image source: Network
ACE2 is a very useful enzyme in the human body and is an ideal target for the treatment of diseases such as high blood pressure and heart failure. But the "fatal" thing is that this enzyme is mainly distributed on the epidermal cells of the respiratory tract, which will attract the new crown virus to the door, which in turn will cause the new crown pneumonia.
What is more "fatal" is that ACE2 is mainly distributed on the epidermal cells of the lower respiratory tract, that is, deeper in the lungs. This has led to a shallow location of the upper respiratory tract throat swab sample, the most important indicator of clinical diagnosis, which is also one of the reasons for the higher negative rate. Some patients do not test positive for throat swabs until CT shows "white lung.".
Academician Wang Chen, vice president of the Chinese Academy of Engineering and president of the Chinese Academy of Medical Sciences, pointed out in an interview with CCTV on February 5 that the detection rate of nucleic acids for real cases is only 30%-50%. There are still many false negatives by taking throat swabs from suspected cases.
This is one of the reasons why many frontline doctors are calling for the diagnosis of new crown pneumonia with lung CT. Today, both CT and nucleic acid testing are included in the diagnostic conditions [2].
Why is there a false negative? In addition to kit performance, the characteristics of this cunning virus and the location of sampling are important factors. The new crown virus first attacks not the upper respiratory tract, but the alveoli located deep in the human body, so the concentration distributed in the lungs is the largest, and the best sampling site is naturally the lungs.
However, in order to collect the lavage fluid of the alveoli, it not only requires special instruments, the operation is complicated, and the damage to the human body is very large.
Therefore, clinical lung sampling is only performed for severely ill patients with ventilators. The suboptimal sampling site is sputum, but many new crown pneumonia patients have no sputum, it is difficult for women to cook without rice, and the most common and simplest sampling method can only be throat swabs. However, the amount of new coronavirus in the pharynx is the smallest, which is often prone to missed tests.
Feature 2: Precise attack on the alveoli, the type of inflammation is special, resulting in cough and fever symptoms are not obvious
The goal of the coronavirus after entering the human body is clear – to go straight to the alveoli and quickly activate the body's inflammatory response to attack the lung tissue [3]. There is no neural tissue in the alveoli and does not trigger cough reflexes, so many patients in the clinic do not cough much.
In addition, the type of inflammatory response activated by this virus may be different from the common type of inflammatory response, which leads to fever in some patients.
In the first-line clinic, many confirmed patients have no obvious symptoms, and the lung CT has appeared lesions, but there is still no cough and no fever, which brings certain difficulties to the diagnosis. The characteristics of no obvious symptoms also make many infected people unaware that they are sick, and still move in the community like healthy people or even travel, which is easy to cause the spread of infection.
In the case of the latter, asymptomatic infected people bring the A-B-C-2B chain of transmission. Among them, A refers to the contact person who lives in the patient; B refers to the contact who is unaware of the journey; C refers to the contact at the destination; and 2B refers to the person infected by B. This is also an important reason why the epidemic has spread so quickly.
For example, according to Anyang Daily, a woman returned to Anyang, Henan Province, from Wuhan on January 10, without any symptoms, but in the following 17 days, five of her relatives were diagnosed with new coronary pneumonia.
Image source: Network Super Spreader
Feature 3: The intestine also has the "key" of the new crown virus, and the fecal-oral and toilet sewers may become a hidden danger of transmission
As mentioned earlier, angiotensin-converting enzyme 2 (ACE2) is an important receptor for the new crown virus, which is the "key" to open the "door" of the cell.
In addition to the lungs, ACE2 is also distributed in intestinal epidermal cells, so some patients with COVID-19 develop diarrhea, and the digestive tract may be another potential route of infection for COVID-19 [4].
In fact, following the announcement by the team of academicians Zhong Nanshan and Li Lanjuan that the patient's fecal samples had successfully isolated the virus, on February 13, the Team of the Chinese Center for Disease Control and Prevention successfully isolated two strains of the new coronavirus from the stool specimens of the confirmed cases of new coronavirus.
Therefore, although the Diagnosis and Treatment Plan for Pneumonia Infected by novel coronavirus (Trial Fifth Edition)[2] still points out that transmission routes such as aerosols and digestive tract have yet to be clarified, the possible potential risks of fecal-oral transmission and home sewer transmission still arouse people's concerns. After all, the "Hong Kong Taoda Garden Incident" brought by SARS was a lesson from the past.
To sum up, let's take a look at the "smoke bomb" released by the new crown virus.
For its gene transmission, it also challenges nucleic acid detection techniques, early screening and identification of suspected patients, as well as traditional understanding of the transmission route of respiratory infectious diseases.
As soon as the infection enters the human body, it quickly flashes through the upper respiratory tract and goes straight to the lower respiratory tract to infect the lungs; and then another runoff is channeled to the digestive tract to establish a second base, while avoiding the most easily sampled area of blood.
Deep incubation, escaping the general epidemiological observation period, has the characteristics of ultra-long incubation period + hidden transmission.
And all of this lays a solid foundation for SARS-COV-2 to become a "cunning virus."
In the coronavirus family, the new coronavirus is smarter than its "brothers"!
In fact, the coronavirus can be said to be the "old friend" of mankind. In addition to the new crown virus, there are 6 kinds of coronaviruses known to infect humans, of which the human coronavirus 229E, OC43, NL63, HKU1 causes very mild symptoms, basically similar to the common cold mild respiratory symptoms.
Perhaps because they are despised and disgruntled, the three brothers of the coronavirus family have "unveiled things" in the past 20 years, introduced to humans by the primitive natural host bat, through the intermediate host (civets, pangolins), and triggered a global public health event. They are notable for SARS (SARS) in 2003, MERS (Middle East Respiratory Syndrome) in 2014, and SARS-COV-2 (new crown pneumonia) in 2019.
So, what are the characteristics of the "three brothers" of highly pathogenic people infected with the coronavirus?
SARS: contagious center, persistent hyperthermia is the main manifestation
SARS has left an indelible shadow on the Chinese people, and has also promoted the construction of a 4-hour direct reporting system in the disease control system, making China one of the countries with the best public health system construction. However, SARS can also be said to be a "mysterious" virus. In the summer of 2003, it quietly went away. It is as if it is not humanity that has overcome it, but that it has spared humanity.
High fever is the most important indicator for the first time to judge a patient with SARS suspected. At that time, there were body temperature measurement instruments everywhere, and if a fever was found, it was immediately checked, and the virus carriers could be screened out quickly, isolated and treated, and the transmission was blocked.
Sars is more contagious than MERS in comparison. It is generally estimated that the number of people infected per capita, also known as the basic number of infections (R0), is between 2 and 3, which is equivalent to an average of 2-3 people infected by 1 patient.
Its mortality rate began as alarming, reaching 17 percent, before being crushed to 6.55 percent, compared to the global average of 10 percent.
MERS: Menacing "stunned", but not very spreadable
MERS is not "impressed" in the hearts of the Chinese people, and it mainly ravags our close neighbor South Korea. When donating epidemic prevention materials to 12 cities in China, Seoul Mayor Park Won-soon said: "Thank you to Beijing for helping us during the MERS epidemic."
MERS has a "grumpy" temper, with a short incubation period (1 to 2 days) and then a rapid fever. Patients are basically seriously ill, in addition to causing severe lung infection, respiratory distress, but also kidney failure.
It has the highest mortality rate, as high as 40% in the Middle East; after infection to South Korea, it was reduced to 20% due to improved medical conditions (186 infections, 38 deaths).
In terms of contagiousness, MERS's R0 is only 0.7, and the epidemic soon tends to converge. That's because MERS is too strong, patients die too quickly, and there is a lack of opportunity for infection to spread.
Coronavirus: Mild, contagious, more cunning than two brothers
The novel coronavirus is not quite the same as its two brothers. Its epidemiological features are gradually "flu-like": the symptoms are not obvious during the incubation period (compared to the high fever of SARS), and the infection rate is extremely high. According to a reviewed literature estimate of 8866 cases, its R0 is about 3.77, that is, the average number of infected patients is much higher than the previous R0 estimate of 2.2 [5].
Many of the infected people are mildly ill and have a low fatality rate, so that they do not kill the host too quickly. And there are many asymptomatic infected people or people who are called poisoners, but they can transmit the virus to others, which is overwhelming.
Imagine if many carriers of an infectious disease have no obvious symptoms but can infect others, how can we find out from thousands of people? Let the whole people do reagent testing?
From an economic point of view, of course not! But taking a step back ten thousand steps, even if the whole people do kit testing, it is useless. As we have already said above, viral nucleic acid testing is not 100% accurate.
Nature is fair. In fact, the high contagiousness and high harm of an infectious disease are often contradictory. From the perspective of the virus, it does not really want to kill the host, but to expect symbiosis. Most of the fast-spreading, highly toxic viruses have long since become extinct or under control. Ebola, for example, was feared by the world with a mortality rate of more than 90% in the early days, and often "annihilated" entire villages in Africa. But killing the host so violently, it is difficult for it to go further.
Among the three respiratory coronaviruses, it now seems that the new crown virus will be a new virus with higher infectivity than SARS, harm and mortality rate significantly lower than SARS.
Write a little thought at the back
Seeing this, we have to sigh that this virus is so cunning that it is almost deliberately designed. Because of this, there have been frequent rumors of "artificial synthesis of the new crown virus" in the recent past.
Of course, this has proven to be a conspiracy theory that exploits panic psychology and is wrapped in a scientific shell. This argument also underestimates the power of nature. It can be said that nature is a laboratory with higher uncertainty. To avoid the ravages of the new virus, the first step we have to do is to fear nature and reject wild game.
Of course, when we say that this virus is cunning, it is nothing more than an anthropomorphic statement, the virus itself has no brain, and all its actions rely on the instincts of biological evolution. As humans at the "top of the planet's food chain," we can certainly find ways to control COVID-19 and any pathogenic microbes that may emerge in the future. But now we may need to think more about how to make the next virus appear no longer as tragic as SARS, and not "ground" us in the home like SARS-COV-2.
This article was written by Zhang Jiecai, editor of Tencent Medical Code
bibliography:
[1] Zhou, P., Yang, X., Wang, X. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature (2020). https://doi.org/10.1038/s41586-020-2012-7.
[2] "Diagnosis and Treatment Plan for Pneumonia Caused by Novel Coronavirus Infection (Trial Fifth Edition)", National Health Commission, February 5.
[3] Yu Zhao, Zixian Zhao, Yujia Wang, Yueqing Zhou, Yu Ma, Wei Zuo，Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov，bioRxiv 2020.01.26.
[4] Zhang,Hao, et al.” The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes.” bioRxiv (2020).
[5] Yang Yang, Qingbin Lu, Mingjin Liu, Yixing Wang, Anran Zhang, Neda Jalali, Natalie Dean, Ira Longini, M. Elizabeth Halloran, Bo Xu, Xiaoai Zhang, Liping Wang, Wei Liu, Liqun Fang，Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China，medRxiv 2020.02.10.
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