Wednesday , February 24 2021

Weakened immune system: Risk of mutations in antibody therapy – Knowledge



Antibodies from cured patients are a therapeutic alternative to Kovid-19 – especially for patients with a weakened immune system. But doctors have long been concerned that mutations could develop well then. If a person’s immune system is weakened due to chemotherapy, it is difficult for the immune system to fight the virus successfully. “Administered antibodies are not supported by cytotoxic T cells at all, which reduces their ability to eradicate the virus,” according to a recent study by British researchers in the journal Nature.

Infections are often chronic and there is a risk that the virus will mutate and develop new traits. There will be variants in which serum therapy is less effective, especially with regard to serum therapy, which is associated with donor antibodies. The effect may be similar to that of an effective vaccine.

More than three months, the genetic sequence is 23

Researchers at the Genomics UK Conference had the opportunity to follow the link between 101 days of chronic infections, mutations and serum therapy in an immunocompromised patient. The British patient was over 70 years of age and suffered from cancer of the lymphatic system of the mucous membranes. His immune system was weakened by chemotherapy. When he became infected with Sars-CoV-2, he was first treated with serum therapy. At first his condition stabilized but later deteriorated considerably. He died despite further treatment. During those 101 days, 23 virus samples were taken and genetically modified. This made it possible to see how the virus mutated.

After two treatments with antibody serum therapy, the researchers observed a clear difference in the virus population between days 66 and 82. A type of virus that survived immunotherapy was predominant. On the one hand, it has a double so-called deletion, which results in the loss of two amino acids in a protein.

Evolutionary competition with the effect of therapy

This difference, called H69 / V70, is close to the receptor binding site of spike proteins, which the virus uses as a key to invade cells. There is another variant called D796H. The combination causes a structural change in both proteins. Administration antibodies do not match well and make it more difficult to neutralize the virus.

Initially, the virus took a back seat, but after the third round of treatment, it experienced another increase. Ravi Gupta, author of one study at the Cambridge Institute of Therapeutic Immunology and Infectious Diseases:

In people with a normal immune system, the virus is not expected to mutate as a result of serum therapy, as in patients with weakened immune systems. In these cases, the antibodies are adequately supported by the cytotoxic T cells of the immune system. These can identify and eliminate infected cells. Antibodies and cytotoxic T cells are more likely to close the virus together.

Isolate patients as much as possible

Using H59 / V70 deletion or D796 mutation or both artificially created viruses, British scientists were able to determine the cause of the mutations. In laboratory tests without antibodies, deletion alone doubles the virus infection compared to the older virus strain. It is important that the deletion of H69 / V70 also occurs in the “British” variant B.1.1.7.

In contrast, D796H is a so-called salvation mutation. The antibody binding site has been modified so that the antibodies of 19 healthy Kovid patients can no longer catch the virus. This reduces the effectiveness productivity of serum therapy. “Since both vaccination and therapy target the mutated spike proteins in our patient, our study suggests that proper mutation of the virus makes vaccine overdose the most worrying option,” he said.

However, “these viruses are less likely to occur in patients with an active immune system, as better immunization controls may reduce the risk of viral infections.” But serum therapy has promoted the selection of virus strains that are less sensitive or less sensitive to antibodies, and there is at least one non-immunized Kovid-19 patient in the United States. “It shows how careful we should be in treating patients with immunodeficiency who have more time to multiply the virus, which means they are more likely to mutate,” the study authors wrote.

Limited use

Unless more data are available, researchers recommend that serum therapy for immunocompromised patients be performed only as part of studies and in individual rooms with precautionary measures to control the increased risk of viral mutations. Special care should be taken to prevent others from becoming infected. Continuous sequencing of the virus is also required.

It is now known that serum therapy is successful only under certain conditions, even in 19 patients with immunodeficiency. The U.S. Food and Drug Administration (FDA) has now restricted its use for this reason: it should only be used in the early stages of treatment in the first 72 hours, and in patients whose immune cells are not producing enough. Antibodies for protection.


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