Since April, the epidemic caused by the new crown virus has spread on a large scale in India. The World Health Organization (WHO) pointed out two important reasons when analyzing the epidemic situation in India. One is the failure to implement effective isolation measures, and the other is the mutation of the new coronavirus.
How dangerous is the double mutant virus?
All microorganisms change in the process of adapting to the environment, and pathogens that cause people to get sick, such as viruses and bacteria, mutate more frequently and rapidly. The new coronavirus is a virus that mutates quickly. There are no exact numbers for how many variants of the new coronavirus are there, and researchers estimate that there are thousands of them.
Researchers believe that the double mutation of the new coronavirus is one of the important reasons for the worsening and large-scale spread of the epidemic in India. On the spike protein (S protein) of the new coronavirus, the coronavirus variant B.1.617 found in India exhibits two gene mutations: E484Q and L452R. E484Q is similar to E484K. The latter has previously appeared in virus variants in the United Kingdom, South Africa and Brazil; L452R has appeared in the California variant of the United States.
These two mutations first appeared in India at the same time, and they were called Indian double mutant viruses. Whether the double mutant virus is twice as infectious or dangerous than other mutant viruses requires more research in the future, as well as data on the clinical symptoms and mortality of the virus to prove it, but the preliminary understanding is that this This double mutant virus strain may have a stronger immune escape ability, so it may be more likely to infect people. Moreover, even those who have been vaccinated or who have recovered from the disease may be rapidly infected again.
However, the prevalence provided by the genome data shows that the transmissibility of B.1.617 is comparable to that of the B.1.1.7 mutant in the United Kingdom, but higher than that of the B.1.351 mutant in South Africa. B.1.1.7 is the first novel coronavirus mutant strain discovered in the United Kingdom from December 2020 to January 2021. Its spike protein (S protein) has an affinity for ACE2 receptors on human cells that has increased 1,000 times. The WHO notified that the B.1.1.7 strain is easier to spread from person to person, with an increase in infectivity of 40% to 70%, and a transmission index of 1.5 to 1.7, which is 0.4 to 0.6 higher than the transmission index of the original new coronavirus 1.1. The increase in the transmission index means that the number of people infected with the virus will increase. Moreover, patients infected with B.1.1.7 mutant strains have significantly increased viral loads, and increased viral loads are also related to increased mortality. However, the toxicity of the B.1.1.7 strain has not been enhanced.
Virus mutations are divided into three categories, which ones should be the most concerned
According to the severity of the impact of the mutation of the new coronavirus on the development of the epidemic, mutant viruses can be divided into three categories: variants of concern (VOI), variants of concern (VOC), and severe consequences variants (VOHC).
Concern about variants means that the virus’s impact on the epidemic is only possible, including: the binding of specific genetic markers to the receptor may change, and the neutralizing effect of antibodies produced by previous infections or immunizations may be reduced. , The effectiveness of treatment methods may also be reduced, and the potential impact of the virus and the disease, the spread of the disease, or the increase in the severity of the disease may be related. It is manifested in several characteristics. One is that specific genetic markers may affect transmission, diagnosis, treatment or immune escape; second, there is evidence that this is the reason for the increase in cases or unique outbreaks, and the third is that the epidemic or expansion in the country and other countries is limited. .
Attention to variants refers to the initial changes in the virus, and there is evidence that the spread of the virus variants increases, the disease is more serious, such as the increase in the number of hospitalizations or deaths, and the significant reduction of the neutralizing effect of antibodies produced during previous infections or vaccination. Reduced effectiveness of treatments and vaccines or failure of diagnostic tests.
The severe consequence variant refers to the fact that there is clear evidence that this type of virus will cause the existing preventive measures or medical response strategies to severely fail or reduce the effectiveness, which is manifested as a diagnosis failure, a severely reduced vaccine effectiveness, and even after vaccination. There are a large number of infected cases, or the protection of vaccines against severe illness is very low, the effects of multiple emergency use authorizations (EUA) or approved therapies have been severely reduced, more serious clinical symptoms have appeared and hospitalization has increased.
For the new crown virus concerned about variants, you only need to pay attention to it, and serious consequences variants have not yet appeared. Therefore, what needs to be monitored now is to focus on variants. Previously, WHO only classified the B.1.1.7 variants found in the UK in December 2020, the B.1.351 variants found in South Africa in December 2020, and the P.1 variants found in Brazil in January 2021. To focus on variants. On May 10, the WHO announced that it would classify India’s double variant B.1.617 as a variant of concern because some preliminary data showed that it is more easily spread. At present, there are 4 new coronavirus variants that need to be monitored and monitored globally.
So far, the antibodies produced after vaccination approved for marketing will recognize these variants, so the vaccine has an effect on all the viruses of concern among the new coronavirus variants. A study in the United Kingdom showed that vaccination can reduce the risk of infection by 2/3. Even if the person is still infected after vaccination, the probability of serious disease can be reduced by 2/3, and the infectiousness of the infected person is also low. However, researchers from Emory University in the United States have recently discovered that Modra’s mRNA-1273 vaccine and Pfizer/Biotech’s BNT162b2 vaccine (also an mRNA vaccine) have a greater reduction in the neutralizing efficacy of the B.1.1.7 mutant. However, the antibodies in the serum of all vaccinators still have significant neutralizing activity to B.1.617, indicating that the current vaccine is still effective against the B.1.617 variant.
The mechanism of virus mutation
Virus mutation is the need to adapt to the environment and survival. This is not only a general summary, but some of the theories and hypotheses have been proved by basic scientific research and clinical medicine.
First of all, the relationship between viruses and humans or other organisms is mutual growth and mutual restraint. In order to cope with the chasing and killing of the immune system in the human body and other organisms (collectively referred to as the host) in order to survive in the host for a long time, the virus will inevitably mutate to avoid the identification and hunting of the host immune system. The most typical virus in this regard is HIV. Due to its extremely rapid and diverse mutations, humans have not yet developed a vaccine against AIDS.
Secondly, for the same purpose of survival, various microorganisms have to fight or even kill each other in order to compete for the living space in the host. Therefore, the virus is forced to mutate more powerfully. On the one hand, it can defeat other microorganisms in the host and occupy more. The site, on the one hand, is also to deal with attacks from the host’s powerful immune system.
Another situation is that the host itself is a platform for microbes to exchange information and genetic components. The reason why influenza A viruses can infect both poultry, pigs and humans is because some viruses can exchange genes in different poultry, pigs, and humans, thereby infecting animals and humans. Moreover, there are 16 subtypes of hemagglutinin (H) of influenza virus and 9 subtypes of neuraminidase (N). These antigens can exchange each other to form dozens or even hundreds of combinations, becoming a new type of influenza. Viruses not only enhance toxicity and infectivity, but also infect humans and different animals.
Another case of virus mutation is determined by the structure of the virus. Generally speaking, DNA viruses are not easy to mutate, because DNA is a double-stranded structure, even if there is an error in one chain during the replication process, the abnormality can be corrected by the other chain, so the mutation rate is relatively low. This type of virus has herpes virus. , Hepatitis B virus, etc. Relatively speaking, RNA viruses are easy to mutate because they are single-stranded viruses. If errors occur during replication, there is no other chain to correct the errors. Therefore, the mutation rate is relatively high. Such viruses include new coronaviruses, coronaviruses, and influenza. Virus, hepatitis C virus, etc.
Virus mutations in many cases will lead to increased virulence, infectivity and toxicity, and therefore will affect the development of the epidemic. Just like the current mutation of the new coronavirus, it will cause difficulties in diagnosis and treatment, and may reduce the cost of vaccines and drugs. Effectiveness. However, virus mutation also follows a basic principle, that is, it cannot become too toxic. If it is too strong, it will quickly kill the host, and they will also perish. Therefore, nowadays viruses with more mutations become less highly toxic, while those with less variability are highly toxic, such as Ebola virus, which is very lethal.
▲ The 1918 flu scene
Comparison of New Coronavirus and Influenza Virus
The new coronavirus is a low-virulence virus. Although its variability is strong, the toxicity found so far is not strong. This may also be determined by its survival strategy. They are similar to influenza viruses, so influenza viruses can be used as an example.
The 1918 pandemic was an extremely deadly influenza pandemic that broke out from January 1918 to December 1920. At that time, about a quarter of the world’s population (500 million people) were infected, causing 20 to 50 million deaths. One of the most deadly epidemics, second only to the Black Death.
In general, influenza outbreaks usually lead to deaths of the elderly, young children, or immunocompromised patients, but the population with the largest number of deaths from the 1918 influenza pandemic was the young and middle-aged. Subsequent studies showed that, first of all, the mutation of the influenza virus caused the high infection rate of the 1918 influenza pandemic. One hypothesis is that by analyzing the gene sequence of the 1918 pandemic virus, it was found to be similar to the H5N1 virus that occurred in Asia in 2005. Another hypothesis is that the virus at the time came from a reassortment of a human H1 virus and an avian virus.
The virus that caused the 1918 pandemic, despite its genetic recombination and mutation, is not very toxic, but its infectivity has increased, with an infection rate of up to 50%. A special case after influenza virus infection is the generation of a cytokine storm, which leads to an overreaction of the autoimmune system. Therefore, young adults with strong immunity are likely to cause a strong immune response and die.
The new coronavirus and influenza virus have greater similarities and are low-virulence viruses. The mortality rate caused by the new coronavirus is about 2.1%, and the mortality rate for influenza is even lower, about 0.1%. However, there are a few coronaviruses that are highly toxic. For example, the coronavirus that caused severe acute respiratory syndrome (SARS) in 2003 was regarded as highly virulent, causing a case fatality rate of 7% to 15%. It is also regarded as a highly virulent virus that quickly kills the host and will quickly lose the chain of infection. An example of.
However, it is difficult to predict how the new coronavirus will change in the future and can only be closely monitored. Even the mutated, low-toxic new coronavirus may trigger a cytokine storm and cause more deaths. However, due to the recognition of this situation, the death rate caused by the new coronavirus has now fallen sharply.
The main causes of death of new coronary pneumonia are respiratory failure, septic shock, heart failure, bleeding and renal failure in order. Cytokine storm is related to the severity and mortality of new coronary pneumonia.
Is the cytokine storm saved?
Cytokines are a group of low molecular weight extracellular signal proteins that are secreted and produced by various immune cells, including macrophages, lymphocytes, mast cells, and other types of cells, such as endothelial cells. There are many cytokines in the human body, including interleukins, interferons, lymphokines, chemokines and tumor necrosis factor.
When the new coronavirus infects the lungs and other parts, a variety of cytokines will stimulate the body’s immune system to eliminate pathogens, such as a large number of antibodies and killer T cells to attack the virus, remove damaged cells, and repair damaged tissues. The condition also produces severe inflammation and may get out of control, which can then lead to septic shock, multiple organ damage, and even eventually to organ failure and death. Many patients with new coronary pneumonia died of respiratory failure, septic shock, and heart failure caused by a cytokine storm.
At present, there is no specific medicine for new coronary pneumonia, but first you can choose antiviral drugs, such as fabinavir, ribavirin and other broad-spectrum antiviral drugs, and anti-influenza virus drugs, such as nitazoxanide.
There is no specific treatment for cytokine storm. The most commonly used and effective drug to directly reduce the cytokine storm is still glucocorticoid, which is also the most commonly used immunomodulator. However, the WHO clinical management guidelines for new coronary pneumonia (released on January 28, 2020) suggest not to use cortex Steroids, unless otherwise stated. However, there are also some targeted therapies for specific cytokines in the cytokine storm, such as monoclonal antibodies or aptamers for specific cytokines, specific recombinant proteins, etc., or the use of anti-interleukin-6 receptor monoclonal The antibody tocilizumab is used to eliminate cytokine storms.
However, the recent development of the epidemic in India also shows that the new crown virus is also different from the influenza virus, and its toxicity is obviously stronger than that of the influenza virus.
India’s new coronavirus double mutant strain B.1.617 was discovered in October 2020 and has now been detected in more than 40 countries. Sinnaswamy, a researcher at the National Institute of Biological Genomics of India, said that a triple mutant strain of mutant new coronavirus has now appeared in India. In addition to the E484Q and L452R gene mutations, the virus also has the E484K gene mutation, the latter first in South Africa Mutated strains in Brazil and Brazil. This triple-mutated strain is now named B.1.618 (abbreviated as Indian strain), and its spread is stronger than other mutant strains.
Although it is believed that the triple mutant virus in India is more virulent, there is currently no definite evidence that the triple mutant virus is more deadly or spread easily. Moreover, researchers have successively detected four-fold and five-fold genetic mutations in other virus samples. At present, these mutations have not yet affected the effectiveness of existing vaccines. However, now vaccine research has also targeted mutant strains of the new coronavirus.