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Covid-19 Immunity Insights Help Scientists Fight Viruses — Quartz

 


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Scientists only discovered SARS-CoV-2, a new coronavirus that causes Covid-19 late last year. On the other hand, most of our immune system has never heard of it. For now, millions of people infected with the novel coronavirus have to rely on their bodies rather than vaccines or targeted drugs to fight off the virus.

The good news: Evolution designed the immune system to do that. Bad news: That response is not always predictable. The immune system is complex in its own right and varies greatly from person to person. This makes it difficult to know when and how to intervene when it gets overwhelmed.

To delay the spread of Covid-19, it is important to have an accurate understanding of how the immune system deals with the disease.

Scientists understand the basics of the immune system. In a new viral infection, the body first develops T cells called CD4 and CD8, which find and kill the infected cells. After about a week, the adaptive immune system is activated and B cells are used to make antibodies even faster that can flag diseased cells for elimination. These antibodies attach after the infection is complete, in case of future invasion.

Its general framework helps you understand the common features of Covid-19. Many people using Covid-19 became ill with two waves. At first they were tired and tired, but then they are likely to recover. “Basically, T cells work, which makes people feel better,” says Juanita Mora, an immunologist and Chicago medical spokesperson for the American Lung Association.

That short recovery can give a false sense of security. T cells may keep the virus away for some time, but if the infection persists, the body needs to make more, even when certain antibodies are ready to act. When this happens, the immune system releases a version of that body slum. The cytokine storm was named after a chemical signal that initiates a fever to kill the virus. However, all of that heat and inflammation can also be severe in vital organs and can cause a particularly serious reaction in people with underlying illnesses.

There’s a lot we still don’t know about everything we know about this immune response. We do not know how well the T cells work (they tend to age) or when they become depleted during infection. Also, when are the correct B cells ready for SARS-CoV-2 specific antibodies, what levels of antibodies may provoke a severe immune response, and a meaningful way to fight in the future? I also don’t know how long the antibody lasts with infectious diseases.

Knowing these details is key to designing the right tools to help manage Covid-19’s epidemic and mortality, including testing, treatment and vaccines. Below, we discuss the science of the immune system that has guided them so far, and the other knowledge needed to complete each part of the anti-coronavirus weapon.

Under test

One of the first ways scientists can start understanding the immune response to SARS-CoV-2 is Serology, A blood test looking for clear antibodies produced by B cells.

The test works as follows: The diluted blood sample passes over a surface that is studded with molecules that mimic the antigen. This is the part of the virus that the immune system can identify. If there are antibodies in the blood, they bind to the antigen and a test reveals a color.

Designing such a test requires a balance of sensitivity, or detectability Any Antibodies, and specificity, ability to detect antibodies to this virus alone. Early Chinese tests dispersion In the United States, for example, sensitivity was 87.3% and specificity was 100%. That is, false positives are not displayed, but 12.7% of cases are missed. First test to take the official FDA approvalCellex’s sensitivity is 93.8% and specificity is 95.6%.

Despite their accuracy, these tests are not ideal for diagnosing current infections. It may take at least one week after the symptoms appear for the antibodies to become detectable. However, they can identify past infections. This is the key to knowing when social restrictions can be relaxed.

“Serologic studies are very important in understanding the extent of population immunity, and how immunity weakens over time,” said Yonathan Grad, an immunologist at Harvard University T.H. Chang Public Health School. “And what will the incidence be in the next few years?” CDC And others have begun such research.

However, it remains unclear how persistent the resistance to SARS-CoV-2 will be and whether it will be the same for everyone. Research on coronaviruses behind SARS and MERS Indicated Antibodies remained in the blood for several years, but their ability to neutralize pathogens diminished over time.

Chinese data on SARS-CoV-2 already available Show Wide range of antibody reactions. In the group of 175 patients, 70% produced high levels of antibodies (called titers). The rest succeeded in fighting off the infection with minimal titers, suggesting that they had defeated the virus in the T cell response or other parts of the immune system. That’s fine — but those people may not have long-term immunity.

The concentration of antibody that can be detected in a test may differ from that which can give a lasting immunity, soImmune passportCan be difficult to implement. Even if you design a test that reflects true immunity, the results may not be accurate. Thanks to epidemiological statistics,

Zachary Vinnie, an epidemiologist at the University of Zamory, Explained like this: Suppose you have a group of 100 people, 10 of which are infected. As with most serologic tests on the market today, there are tests that are 90% effective in correctly identifying both positive and negative cases. That is, you get 9 correct positives and 81 correct negatives, plus 9 false positives and 1 false negative. Out of a total of 18 positives, only 9 were actually infected with the virus (and one was actually allowed). So the positive result is exactly half the time. But when 40 people get infected and the accuracy jumps to 89%, try the math again.

In other words, more people need to catch the virus before being frustrated and better understanding how immunity actually spreads.

Treatment

Antibodies can also be used to develop treatments for sick people. Last month, Houston hospital Became the first In the US, severe Covid-19 patients Plasma therapyDeliver antibody-loaded plasma from the recovered patient to the still sick patient. Tests are currently being conducted at several other hospitals in the United States. As of last week, Mount Sinai Hospital in New York Accepted 125 people donated plasma and 37 blood transfusions given to critically ill patients.

It’s too early to see how effective these treatments are, says Michael Joiner, a Mayo Clinic physiologist who leads the effort. However, one of the main advantages of plasma therapy is that the body does not need to know the details of the body’s immune response in order to function. That is, you can trust your body and only others can perform its function.

However, donating blood plasma is currently difficult to obtain in the required amount. Many pharmaceutical companies Develop medicine Large-scale replication of specific antibodies and pack them into shots.

The first step in the process is to study the antibodies in plasma provided by the recovered patient. Some antibodies, known as bound antibodies, attach to the virus only to flag it for destruction. Others, known as neutralizing antibodies, attach in a way that physically prevents the virus from entering human cells and replicating.

Pharmaceutical companies usually want to focus on neutralizing antibodies. Based on their compatibility with the virus’ unique protein structure, some neutralizing antibodies play a role over others. Some companies have chosen to use specific neutralizing antibodies that appear to work best. Others mix cocktails, but they also help prevent treatment from becoming obsolete if the virus mutates.

We also do not know what combination and concentration of antibodies can cause a storm of cytokines or extensive inflammation that patients want to avoid. This type of reaction was recorded last year in a study of laboratory monkeys receiving antibody drugs after being infected with an older SARS. Many pharmaceutical companies developing antibody therapies are looking to start trials over the coming weeks, hoping that safe and effective options will be available by the fall.

vaccine

Ideally, with the help of a vaccine, you can finally prevent Covid-19 infection. Vaccines urge the body to prophylactically produce specific antibodies against pathogens. When an infection occurs, the vaccine already eliminates the delay between the innate immune system’s response and the adaptive immune system’s response to one and only one infection.

As of April 8, Over 100 Covid-19 vaccines During development, it uses a variety of tactics to drive the immune system. Vaccines present the biological characteristics of pathogens to the immune system. Some use proteins or peptides, some use fragments of genetic material encapsulated in other viruses, some use weakened or immobile fragments of the pathogenic virus itself.

Most of these targets are inspired by vaccines against similar pathogens Have worked safely in the past—Or at least thoroughly investigated. As scientists were developing Ebola and MERS vaccines, vaccine candidates were mobilized to use the benign virus to transport some of the spike proteins of SARS-CoV-2 into the body. Nanoparticles made to deliver lab-made antigens to target the spike proteins of SARS are being revived by the pharmaceutical companies that abandoned them when the crisis was no longer imminent.

Theoretically, both of these strategies motivate B cells to develop antibodies against SARS-CoV-2 and keep them in the body just enough to prevent suffering from infection.

But, after all, scientists don’t know the details of how B cells acquire immunity to the new virus. Some SARS-CoV-2 vaccine candidates have begun Phase I trials to see if they have any dangerous side effects, while others are still in the pipeline or undergoing animal safety trials .

In the resulting race, there will be a handful instead of just one. “Of the 50 or 80 candidates, 3 or 4 may be effective,” says Mark Poznansky, director of immunology at the General Hospital Vaccine and Immunotherapy Center. . This is the best case scenario. More types of vaccines mean that more people can receive them safely.

However, testing, treatment, and vaccine development must all keep up with the continuous update of our understanding of the virus.

“We want moving targets,” said Poznansky. “Basically, the virus has infected humans for millions of years, so this is unlikely to represent a new type of battle. But because most human populations lack immunity, it is It’s like a vast and horrific experiment on our immune system. “



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