On September 9, the Chinese Center for Disease Control and Prevention announced that China has completed preclinical studies of inactivated vaccines for the Delta strain of the new crown virus.
For different variants, various vaccine research and development units in China have carried out research on broad-spectrum or multivalent recombinant protein vaccines. Experts said that although China's inactivated vaccine is still effective against the Delta variant, the new crown virus is still emerging new mutations, and we still need to be prepared, "even if the virus mutates seriously in the future and completely escapes the preventive effect of existing vaccines, it can quickly and large-scale production of new vaccines."
Chart: The World Health Organization ("WHO") reported on 8 September that 174 countries and territories have been infected with the Delta strain.
With the spread of vaccines, the world of shutdown is once again in order. Still, there are many unsolved mysteries:
Why are some people infected with the new crown virus asymptomatic or mild, while others develop severe disease and even lead to death?
Why does the nucleic acid test test be negative, but the lung damage continues to worsen?
What causes the emergence of "long-term COVID-19" symptoms?
What is the reason behind the multi-organ damage that lasts for months in COVID-19 patients?
This can't help but be reminiscent of the recent hit drama "Sweeping The Black Storm", Gao Mingyuan single-handedly covered the sky, Sun Xing was mad, and the vegetable bully Yang Dong was overbearing, which was inseparable from the "protective umbrella" of many dark forces.
The hypocrites of the taoist appearance - Dong Yao, the mayor of the district, who only wants to be promoted to a higher rank and get rich - director Of the Public Security Bureau, and the seemingly righteous and honest "subwoofer" - vice governor Wang Zheng, all use their own powers to "whitewash" the dark forces. Is it true that the human body is also like the green vine city, lurking in the "umbrella" of "whitewashing" the new crown virus?
"Rogue" antibodies "surface"
In the early days of the COVID-19 pandemic, many researchers believed that some people had an overactive immune response to COVID-19 infection. Alen Rena, an immunologist at Yale Medical School in the United States, said that antibodies are essential to fight off infections, but some new crown patients will produce antibodies that damage their own cells and tissues, that is, autoantibodies. Of course, these antibodies may also be present before the patient is infected.
A large international study published august 16, 2021 in the journal Science Immunology, also showed that when some people are infected with COVID-19, there is an autoantibody in the human body that attacks the autoimmune defense system and becomes a key factor in the development of the disease into severe illness and even death.
Some scientists, in order to emphasize its reaction mechanism, jokingly call autoantibodies "rogue" antibodies.
"Rogue" antibodies are antibodies that target their own tissues, organs, cells, and cellular components. In addition to being present in patients infected with COVID-19, it is also present in a small number of healthy individuals who have not been infected with COVID-19, but the level is not too high to cause damage or attack to the immune system.
The "rogue" antibody is originally a member of the human organism, but it attacks the autoimmune defense system to "pave the way" for the invasion of the new crown virus, and some netizens joke that autoantibodies are the "leading party" of the new crown virus.
In 2021, the internationally renowned journal Nature published three articles on "rogue" antibodies.
The first, published on January 19, titled "'Rogue' Antibodies May Trigger Serious COVID-19," said that "rogue" antibodies are a key factor in exacerbating the condition of people infected with covid-19;
The second was published on January 23 and is titled "'Rogue' Antibodies and Coronavirus Mutations";
The latest article was published on August 31: "Nearly 1 in 5 of the dead COVID-19 patients have 'rogue' antibodies in their bodies."
Search for "rogue" antibodies
Studies have shown that this antibody increases the body's prevalence with age, which may help explain "why are older adults at higher risk of severe COVID-19?"
Compared with the coronavirus epidemic that spread geometrically and devoured life, the scientific community's research on "rogue" antibodies seems to be somewhat hindsighted, but in fact, it did not start very soon. In September 2020, a research team led by Jean Laurent Casanova of Rockefeller University in New York reported that more than 10% of the 987 patients with severe COVID-19 had antibodies that attacked their immune system and blocked the action of type I interferon, which plays a key role in fighting viral infections.
"It's a staggering percentage because people's antibody stocks often vary widely, and none of the control groups in the study had these antibodies." The researchers also found that people had "rogue" antibodies before they were infected with the new crown pneumonia virus, so Casanova believed that these antibodies may have a "genetic predisposition".
He also found that "rogue" antibodies are more common in men than in women, which may be a factor in the more susceptibility of male COVID-19 patients to severe illness.
"Rogue" antibody neutralizes type I interferon Image source: Reference [5]
The research team focused on detecting "rogue" antibodies. They studied 3,595 patients with severe COVID-19 in 38 countries and found that 13.6% of patients detected "rogue" antibodies, of which 9.6% were under 40 years old and 21% were over 80 years old. In 18% of those who died, "rogue" antibodies were present.
Proportion of "rogue" antibodies in 3595 severe COVID-19 patients (Image source: References)
Casanova and colleagues suspect that these antibodies are a cause of COVID-19, not a consequence.
There are traces of such conjectures. The research team has found that for every 1,000 healthy human samples collected before the outbreak of the new crown epidemic, 4 samples have "rogue" antibodies. They also found that individuals with gene mutations that disrupt interferon type I activity were at higher risk of fatal disease.
In response to this finding, the researchers took blood samples from nearly 35,000 healthy people and looked for "rogue" antibodies from them. They found that 0.18 percent of people aged 18 to 69 had "rogue" antibodies against type I interferon, and that percentage increased with age—1.1 percent of people aged 70 to 79 had "rogue" antibodies against type I interferons, and 3.4 percent of people over the age of 80 had "rogue" antibodies against type I interferons.
Proportion of "rogue" antibodies in 34,159 uninfected patients (Image source: References)
The above findings have clear clinical significance, so it is recommended that hospitals conduct timely testing for the presence of these "rogue" antibodies and whether they carry interferon-related mutations that block type I, which will help to find people who are more susceptible to severe COVID-19 and help doctors adjust treatment plans appropriately.
Other research teams have also responded to Casanova's "rogue" antibody theory. Iwasaki, Rena et al. screened 194 patients and hospital workers with different severities of COVID-19 for a wide range of "rogue" antibodies.
Studies have found that people who have "rogue" antibodies to attack the immune system in infected people have a higher prevalence than uninfected people. They found that "rogue" antibodies attack both B cells and interferon molecules (the study was not peer-reviewed).
In addition, the new crown virus may induce the body to produce "rogue" antibodies that attack its own tissues. In some infected patients, "rogue" antibodies attack blood vessels, the heart and the brain.
This is intriguing because many of the symptoms seen during the pandemic are related to cardiovascular and cerebrovascular diseases.
What is unclear is whether the new crown pneumonia infection caused the body to start producing these "rogue" antibodies, or whether these infected people already had these "rogue" antibodies in the body before they were infected.
Mike Goldman, former director of the European Innovative Medicines Programme, added that the researchers also found "rogue" antibodies against the phospholipid molecule. A study published in November 2020 found that 52% of 172 hospitalized covid-19 patients carried these "rogue" antibodies. This is a concern for researchers because some phospholipids play a role in blood clotting, and COVID-19 can cause clotting abnormalities, in other words, "rogue" antibodies may make the patient's coagulation abnormalities worse.
Another study (not peer-reviewed) reported that COVID-19 may stimulate the production of "rogue" antibodies. David Lee, Ph.D., an emergency medicine physician at New York University, and Anna Rodriguez, a microbiologist at New York University, and others analyzed serum samples from 86 hospitalized patients with COVID-19 and found that the average level of anti-annexin A2 antibodies in dead patients was significantly higher than that of patients with non-critical illness. Annexin A2, on the other hand, can play a role in maintaining the stability of cell membranes and ensuring the integrity of small blood vessels in the lungs.
As with other studies, it is unclear whether these "rogue" antibodies existed before they were infected with the coronavirus.
To some extent, the "rogue" antibody theory can explain the delay in the appearance of severe symptoms of new crown pneumonia.
"Why does it take a long time after a person has symptoms such as fever that a person has damage to tissues such as the lungs?" David Lee reminds that autoimmunity may be the real culprit for the continued deadly damage caused by the new crown virus after it has been eliminated.
An MRI scan taken at a clinic in Paris showed how COVID-19 damaged a patient's lungs
It's not all bad news: the "rogue" antibodies bring new revelations to the treatment of the new crown
If autoimmune factors make individuals more susceptible to COVID-19, or if they are infected with COVID-19 and produce "rogue" antibodies, then this is of great significance for the treatment of COVID-19. Casanova pointed out that if pre-existing autoimmunity against interferons increases an individual's risk of contracting COVID-19, then tests that detect these "rogue" antibodies can help screen out these susceptible people.
"If infected with the new crown virus, these people can supplement with interferons as early as possible, as appropriate, β, which are not as vulnerable to the immune system as other interferons." Casanova suggested. In November 2020, a preliminary study found that an inhaled form of interferon-β appeared to improve the clinical profile of COVID-19 patients, prompting larger trials of the treatment.
Interferon substitutes are designed to enhance the activity of a weakened immune system. But if "rogue" antibodies attack organs, such as the lungs and brain, a simple strategy against them could be to suppress the immune system.
In fact, before the "rogue" antibody became the focus, there was already a view that the "cytokine storm" may be the culprit, so the researchers tested whether immunosuppressive steroids (such as dexamethasone) or anti-arthritis drugs (such as tocilizumab and saligimab) can stabilize the immune system abnormalities caused by the new crown.
The World Health Organization "strongly recommends" the use of dexamethasone in severe cases. A clinical trial on 7 January 2021 showed that these immunosuppressants could significantly reduce mortality in intensive care unit patients, and the UK is also using anti-arthritis drugs for patients with severe COVID-19.
At the same time, doctors stressed that whether it is to calm the cytokine storm or try to solve the autoimmunity, the use of drugs needs to choose a careful time so as not to interfere with the human body's fight against the new crown virus.
At the same time, David Lee said that if the "rogue" antibodies against annexin A2 and other proteins are proved to be induced by the new crown, it may be important to remove these antibodies from the patient's plasma in some procedure and then transfuse them back into the patient.
Scientists are very interested in whether autoimmunity is also related to the "long-term coronavirus". First, Rena noted, they don't know if these "rogue" antibodies are contributing to the long-term existence of COVID-19. But if so, how long do these antibodies last? How long does the body continue to produce these antibodies?
The research involved in answering these questions is very complex, because humans naturally produce many different kinds of antibodies, including "rogue" antibodies.
Relevant experts believe that this large sample of data will prompt researchers to consider whether "rogue" antibodies are also acting as "umbrellas" for other infectious diseases.
The epidemic does not wait for people, and the endless mutated strains of the new crown virus will not be caught. The Delta strain is raging, and another variant of the new coronavirus called "Mu" has attracted the attention of WHO. The data shows that the United States has the highest number of cases of Mu mutant virus infection in the world, and as of September 4, the state with the highest proportion of Mu strain cases in the United States is Alaska, the largest, least densely populated and least populous state in the United States.
The latest WHO study shows that the "Mu" variant has a series of mutations that have the potential property of immune escape, which weakens the effectiveness of antibodies, in other words, it can avoid certain antibodies, including those provided by vaccines.
New research results, like pieces of the puzzle, are piecing together laws hidden in the dark, and we believe that the lethal mechanism of the new crown virus will be clearer in the near future.
Source| Health Community - Clinical Frontline
The author | Liu Xueli
Resources
【1】https://www.nature.com/articles/d41586-021-00149-1
【2】 https://www.nature.com/articles/d41586-021-02337-5
【3】 https://www.nature.com/articles/d41586-021-00017-y
【4】 Bastard, P. et al. Science Immunol. 6, eabl4340 (2021).
【5】 Bastard, P. et al. Science 370, eabd4585 (2020).