Recently, everyone may have been screened by news about asymptomatic infections.
Since April, China has officially announced the number of asymptomatic infections daily. This aspect shows the government ’s determination to fight the epidemic and its attitude of not avoiding or concealing. It is worthy of praise; but for the public, it really feels a little nervous and anxious. Imagine that if there are a lot of asymptomatic infections like ghosts in the crowd, it suddenly triggers an outbreak of infection in the community again, making the epidemic that is finally under control resurgent.
According to the official release, asymptomatic infected people can be divided into two situations: First, the infected person has a positive nucleic acid test, and after 14 days of incubation, there is no self-perception The symptoms and signs that can be clinically recognized are always asymptomatic; the second is that the nucleic acid test of the infected person is positive, and there are no self-perceived or clinically recognizable symptoms and signs when sampling, but then some clinical manifestations appear, that is, in The “asymptomatic infection” status during the incubation period.
The “asymptomatic infection” of the incubation period is easier for everyone to understand. But for “always asymptomatic infections” and “determined to be infectious”, you may feel a little mysterious and confused. Although there is currently a lack of scientific research and conclusions on the epidemiological characteristics, infection rate, etc. of asymptomatic infected persons, we can pass some research results of the new coronavirus that have been obtained and some basic facts of known related viruses. Let ’s scrutinize the basic elements of asymptomatic infection (infection, incubation period, symptoms) and try to piece together the true face of Lushan behind her.
First of all, infection refers to the process in which bacteria, viruses and other pathogens invade the human body and grow and reproduce in the body, leading to local or systemic inflammation. Because the virus itself does not have a cell structure and cannot survive independently, it can only survive and replicate in living cells that are parasitic to other organisms, and the virus does not have the ability to invade any cell, only through its own coat protein to accurately bind to the receptor on the surface of a specific cell Only matching can invade, it is a bit like the relationship between “key and door lock”. For example, it is now clear that HIV can only invade CD4 + T lymphocytes, and new coronavirus can only invade the human body through the ACE2 receptor on the surface of respiratory epithelial cells, especially the expression of ACE2 receptor in type Ⅱ alveolar epithelial cells. It is particularly rich, which also explains why the new coronavirus is prone to cause pneumonia. In addition, ACE2 receptors are usually located on the luminal surface of epithelial cells, such as the conjunctival surface of the eyelid. So, you see that patients with new coronavirus are generally not infected, but you rub your eyes with fingers that have been in contact with the virus.Will greatly improve the chance of a stroke.
The period between the time when the virus invades specific cells in the body and the appearance of clinical symptoms is called the incubation period. Under this relatively calm appearance, in fact, as the virus begins to replicate and reproduce in the host cell, the body’s internal immune system will naturally respond and defend against the virus. From a chronological point of view, innate immunity or non-specific immunity comes into play first, that is, macrophages and neutrophils in the blood phagocytose. In the process of phagocytosis of viruses and abnormally infected cells, macrophages also treat The digested virus debris fragments (antigens) are submitted to specific lymphocytes (CD4 + T cells) of the body to induce specific cellular immunity and humoral (antibody) immunity against the virus to jointly kill the virus and the virus invading cells. This process Also called adaptive immunity or acquired immunity. Compared with innate immunity, acquired immunity is more precise and efficient. The final elimination of the virus and the protection of the human body from the same type of virus attacks in the future mainly rely on this type of immunity. And because the HIV virus attacks (parasitic damage), it happens to be the key role of CD4 + T lymphocytes, which will lead to acquired immunodeficiency, and this is the origin of the name AIDS (acquired immunodeficiency syndrome).
For both cases of asymptomatic infection, the above infection and incubation period are actually mandatory stages. Whether or not the symptoms will ultimately depend on whether the inflammatory response exceeds a certain threshold. This threshold actually corresponds to the number of cells invaded by virus infection, but the complexity is that this number is different in different systems and different parts (upper or lower respiratory tract), and even different between individuals. But in general, the threshold is determined by the virulence of the virus and the body’s immune response, and it is dominated by the stronger factor between the two.
Analysis of this new coronavirus infection, the most common clinical symptom is fever (about 90%), followed by cough (about 80%, mostly dry cough), again Difficulty breathing (about 40%), and some less common headaches and muscle aches (about 10% or less). It can be seen that these clinical symptoms of new coronavirus infection are mainly caused by the body ’s autoimmune response (existing studies have confirmed that cough and breathing difficulties are also mainly due to the immune system ’s own Caused by the attack, not from the destruction of the cell caused by the virus). Another example is the symptoms of low fever, fatigue, nausea, and general malaise that occur early after the rabies virus infects the human body. The symptoms are mainly caused by the body’s immune response; but by the middle of the disease, the symptoms are aggravated, and the symptoms of hydrophobia, paroxysmal pharyngeal muscle spasm, and difficulty in breathing and urination, Eventually it develops into paralyzed paralysis until death.These central symptoms are mainly due to the direct destruction of viruses invading brain cells.
Although not the leading factor for symptoms, the virulence of the new coronavirus may affect asymptomatic infection (specifically the first case, in order not to cause ambiguity, for The patients in this situation are referred to as “always asymptomatic patients” in the following text). Common colds caused by coronaviruses (HCoV-229E and HCoV-OC43) are common, but the virulence is weak, and about 70% of infected people do not show symptoms. The lethal rate of influenza caused by the more toxic influenza virus is also much higher than that of the common cold, but about 40% of people will always be asymptomatic [1]. Next is the relatively rare SARS virus and MERS virus. The number of people infected with them is relatively small (the total number does not exceed 10,000), but once infected, the mortality rate is very high (SARS: about 10%, MERS: about 35%). The proportion of those who are always asymptomatic among the two respiratory coronavirus infections is also low, both around 10% [2-3]. From the above information, it can be seen that the stronger the virulence (lethal rate) of the virus, the lower the probability of having an asymptomatic infection after infection. The virulence lethal rate of this new coronavirus is significantly lower than that of MERS and SARS viruses, but higher than that of influenza viruses. Therefore, the consistently asymptomatic infection rate caused by it is logically inferred to be between the two groups of viruses. Between 40%, of course, this speculation needs to be confirmed by more research.
Let ’s take a look at the relationship between acquired immunity and always asymptomatic infection. According to the strength of acquired immunity, it can be roughly divided into three levels: strong, weak, and medium, which can basically correspond to young and middle-aged, old and weak children and the general population. Although there is no research report on the proportion of the above three groups of people in asymptomatic infections, it is clear that stronger acquired immunity can help the body to clear the virus faster and more thoroughly, so the young and middle-aged people should theoretically be among them The highest proportion.
The existing results for the elderly and weak children show obvious polarization, a new article about new coronary pneumonia published in “The Lancet Infectious Diseases” Articles from the Children ’s Epidemiological Survey showed that 10 out of 36 children (mean 8 years old) diagnosed had 10 children (28%) who were always asymptomatic, and the remaining children had mild to moderate symptoms [4] . In another clinical study of “Nature and Medicine”, 745 children with a history of close contact with patients with new coronary pneumonia were tested, and only 10 were tested positive with mild symptoms, of which 1 (10%) did not Any symptoms also belong to those who have been asymptomatic. These results indicate that the acquired immunity of children is weak, so the symptoms after infection are mild and they are more likely to developPeople who are always asymptomatic are now infected.
However, the results for elderly people with weakened immunity show another extreme. This time, the highest proportion of severe and fatal deaths among patients with new coronavirus infections are elderly patients. The cause of death of the “inflammatory factor storm” has also been repeatedly mentioned in official media, and the latter is an important sign of excessive immune response. In fact, overreaction and underreaction are both important manifestations of weak immunity, reflecting the natural law that the precise control of the immune response will gradually weaken with age, so the proportion of elderly people who are always asymptomatically infected is likely to be lowest.
Finally, let ’s focus on the asymptomatic infections of the general population. When the acquired immunity is normal, the immune response intensity is basically adapted to the local infection status of the body. From the structural characteristics of the human body, the threshold of the inflammatory response must be higher in the upper respiratory tract than the lower respiratory tract. The same infection occurs in the upper respiratory tract than the lung (lower respiratory tract) caused by the immune response is milder, which is also clinically observed Consistent, that is, the probability of fever of pneumonia is much higher than that of upper respiratory tract infection. The reasonable reasoning is that the majority of those who have been asymptomatic may be only those with upper respiratory tract new coronavirus infection. Even if they are accompanied by pneumonia, they may only be mild patients and can heal themselves. Because if the pneumonia infection gets worse, the patient will eventually show symptoms and become an asymptomatic infected person in the incubation period. Therefore, this conclusion also applies to all those who have been asymptomatic.
Based on the above analysis, we can deduce the following two hypotheses to be tested and a logical conclusion: 1. The always asymptomatic infection caused by this new coronavirus The proportion of people among the total infected people may be between 10% and 40%; 2. Among those who have always been asymptomatic, the proportion of healthy young adults is the highest, followed by children, and the elderly is the lowest.
A credible conclusion is: the majority of those who are always asymptomatic are only upper respiratory tract new coronavirus infections, and only a small number of infected people may have self-healing mild symptoms Pneumonia, the specific ratio between the two has yet to be verified by clinical studies.
With the above conclusions, we can eliminate unnecessary panic and rationally deal with people who are always asymptomatic. In fact, the asymptomatic infection in the incubation period, the inflammatory response in the body is also below the threshold, and it is temporarily in a mild state. At the same time, because of the absence of cough symptoms and the barrier of the mask, the amount of virus discharged into the air by the patient is further reduced, and the probability of spreading and infecting others is greatly reduced. In addition, all parts of the country have passed strict and sufficient isolation and waiting, so there are currently asymptomatic domestic infections around youThe probability of the person is minimal. However, due to the probability of a large number of hidden asymptomatic infections for foreign immigrants, it also fully supports the current government’s need to respond to the policy of all nucleic acid detection and centralized isolation for returnees, before the epidemic is completely over. It needs long-term persistence to ensure the final victory of the domestic anti-epidemic struggle.
(Author Zhang Yingfan is the Deputy Chief Physician and Doctor of Medicine of the Ninth People ’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine)