Antibodies from recovering patients are a treatment option for Covid-19 – especially for patients with weakened immune systems. But doctors have long worried that mutations could develop well.
If a person’s immune system is weakened as a result of chemotherapy, for example, the immune system is hardly able to successfully fight viruses. British researchers wrote in a recent article in the journal Nature: “The antibodies that are ingested are barely supported by cytotoxic T cells, which reduces the chances of eliminating the virus.” a study.
The infection often becomes chronic and there is an increased risk that the virus will mutate and develop variants with new characteristics. In the case of serum treatment upon contact with donor antibodies, it is particularly those variants against which these antibodies are less effective that they predominate. The effect can be similar to insufficiently effective vaccination.
Over three months, 23 genome sequences
Researchers from the “Genomics UK” consortium had the opportunity to follow the relationship between chronic infection and mutations and serum therapy for a period of 101 days in an immunocompromised Covid patient.
The British patient was more than 70 years old and had a tumor of the lymphatic system, which occurred in the mucous membranes. Due to chemotherapy, the immune system is weakened.
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When he contracted SARS-CoV-2, he was initially treated with serum therapy, among other things. His condition initially stabilized, but then significantly deteriorated. Despite the extra treatment, he died. During those 101 days, 23 virus samples were taken and their genomes sequenced. This made it possible to see how the virus had mutated.
After two treatments with Antibody serum treatment The researchers observed the clearest change in the number of people infected with the virus between day 66 and 82. The type of virus that survived the antibody treatment became dominant. On the one hand, it has what is called a double deletion, as a result of which two amino acids are lost in the protein.
An evolutionary race with a treatment effect
This alteration, called H69 / V70, is near the spiky protein receptor binding site, which the virus uses as the key to invading cells. There is also another mutation nearby, known as D796H.
Together, they both cause a structural change in the protein. It makes the taken antibodies less appropriate and less able to neutralize the virus.
Initially, this mutating virus took a back seat, but after the third round of treatment it saw a renewed spike in numbers.
Commenting on this, one of the study’s authors, Ravi Gupta of the Cambridge Institute for Clinical Immunology and Infectious Diseases, said, “What we saw was fundamentally a competition between different viral variants and we believe this competition is fueled by serum therapy.”
In individuals with a normally functioning immune system, the virus is not expected to mutate as a result of serum therapy, as it is in immunocompromised patients. Because in these cases, the antibodies are adequately supported by cytotoxic T cells in the immune system. It can recognize and eliminate infected cells. Together, the antibodies and cytotoxic T cells have a greater ability to stop viruses.
Isolate patients as best as possible
By using industrially produced viruses containing either the H69 / V70 deletion, the D796 mutation, or both at the same time, British scientists have succeeded in determining the cause of the mutations. In laboratory experiments without antibodies, deletion alone doubled virus infection compared to the old virus. It is also important that the H69 / V70 is also omitted in the B.1.1.7 ‘British’ variant.
In contrast, D796H is the so-called escape mutation. Here the receptor binding site is altered so that the antibodies from healthy Covid 19 patients cannot catch the virus there either.
This reduces the effectiveness of the serum therapy. “Given that both vaccines and therapies target the spike protein that has been mutated in our patient, our study makes the most worrying option that the virus outperforms vaccines by mutating appropriately,” says Ravi Gupta.
However, “it is unlikely that this formation of virus variants will occur in patients with an active immune system, as fewer viral variants could arise due to better immune control.”
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But serum treatment encouraged selection of virus variants that are less sensitive or insensitive to antibodies in this and at least one other patient is immunocompromised in the USA.
“It shows how careful we must be when treating immunocompromised patients, for whom the virus has more time to reproduce, which means it also has more opportunities to mutate,” the study authors wrote.
As long as more data are not available, the researchers recommend that serum treatment of immunocompromised patients should only be conducted as part of studies and preferably in single rooms with increased infection control precautions due to the increased risk of viral mutations. Special effort must be made to prevent injury to others. Continuous sequencing of the virus is also required.
It is also now known that serum treatments only work under certain conditions, even in Covid-19 patients who are not immunocompromised. This is why the US Food and Drug Administration (FDA) has restricted its use now: In the future, it should only be used in the early phase of treatment, that is, in the first 72 hours, and in patients whose immune cells do not produce enough antibodies for defense.
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