How do mutations of the coronavirus arise?
In the case of COVID-19, antibodies from people who have already recovered can be used for treatment. This is especially useful for people with a weakened immune system. However, there are concerns among experts that such a therapy will encourage the development of mutations.
Antibody treatment can actually lead to mutations in people with COVID-19 who have a weakened immune system, according to a study carried out by experts from University College London. The research was published in the English-language journal “Nature“Published.
Antibody treatment for COVID-19?
Antibodies from recovered people can be used to treat COVID-19, which is especially useful for people with a weakened immune system. However, such a treatment has the disadvantage that it can promote virus mutations, especially in people with weak immune systems, explain the researchers.
For example, when people are immunocompromised as a result of chemotherapy, the immune system has great difficulty fighting dangerous viruses effectively. In such a case, the antibodies used in the therapy receive very little support from the so-called cytotoxic T cells. This will reduce the likelihood that the virus will be cleared quickly in the body.
This often makes infections chronic, which increases the risk of a mutation in the virus. This can lead to variants of the virus with completely new properties, reports the team. If antibodies from recovered persons are used in serum therapy, it is primarily the virus variants against which these antibodies are less effective that prevail. The experts also speculate that this effect could be similar if the vaccination was insufficiently effective.
Is there a connection between chronic infection, mutations and serum therapy?
The research group studied the relationship between chronic infection, mutations and serum therapy in a 70-year-old immunocompromised man with COVID-19 for 101 days. The patient had a tumor of the lymphatic system and was treated with chemotherapy, which weakened the immune system.
Effects of serum therapy
When the man fell ill with COVID-19, serum therapy was also performed among other treatments. Initially, this stabilized the condition, but then it progressively deteriorated, culminating in the patient finally dying. Over the course of 101 days, the researchers took a total of 23 virus samples, the genomes of which were sequenced. This allowed the team to watch closely how the virus mutated.
Virus variant survived antibody therapy
The researchers noted that after two treatments with antibody serum therapy, the most pronounced change in the virus population occurred between the 66th and 82nd day. A variant of the virus that survived antibody therapy became dominant. This has a double deletion, which resulted in two amino acids being lost in the protein.
The change, known as H69 / V70, occurs near the receptor binding site of the spike protein. The virus uses this as a kind of key to gain access to the cells, explain the researchers.
Mutations changed the structure of the spike protein
In addition, another mutation (D796H) occurred and together both mutations led to a change in the structure of the spike protein. This meant that administered antibodies were no longer able to adapt and neutralize the virus as well, the team added.
No danger for people with a healthy immune system?
If people have healthy immune systems, the virus is unlikely to mutate through serum therapy, as it does in immunocompromised people, the researchers explain. Because in healthy people, existing antibodies are better supported by so-called cytotoxic T cells. These cells are able to identify infected cells and destroy them. Those skilled in the art add that antibodies and cytotoxic T cells together have a greater potential to eradicate the viruses.
Mutation doubled the infectivity of the virus
The team also created viruses that contained the H69 / V70 deletion or the D796 mutation, or both at the same time. With these viruses, the researchers were able to analyze what the occurring mutations cause. It was shown in laboratory experiments that the deletion doubled the infectivity of the virus compared to the old variant of the virus. The H69 / V70 deletion is also included in the British COVID-19 variant B.1.1.7.
In D796H, the receptor binding site has been changed in such a way that it is no longer as easy for antibodies from recovered people with COVID-19 to detect the virus, which contributed to the reduced effectiveness of the serum therapy, explain the researchers. The virus seemed to outsmart active ingredients used by mutations.
According to the experts, such variants of the virus are unlikely to develop in people with healthy immune systems. This is due to better immune control, through which fewer virus variants can arise.
But the serum therapy promoted the selection of the virus variants that are less sensitive or insensitive to antibodies in the examined person with a weakened immune system, explain the researchers. Essentially, there is competition between different virus variants, which was fueled by the serum therapy.
Exercise caution when treating immunocompromised people
The results indicate that particular care should be taken when treating immunocompromised people, in whom the virus has more time to multiply, as SARS-CoV-2 has more opportunities to mutate in such a case, emphasize the researchers . Serum therapy in people with a weakened immune system should only be carried out within the framework of studies and ideally in single rooms with increased infection control precautions because of the increased risk of virus mutations. The experts also advise sequencing the virus at all times.
Serum therapies are only used to a limited extent
In the meantime, according to the experts, it is also clear that serum therapies are only effective under certain conditions, even in people with a healthy immune system. In the US, the US Food and Drug Administration (FDA) has therefore restricted the use of serum therapies. In the future, such a therapy should only be used in the early phase of treatment (in the first 72 hours). In addition, it can also be used in people in whom the immune cells do not produce enough antibodies for an effective defense, add the researchers. (as)
Author and source information
This text complies with the requirements of specialist medical literature, medical guidelines and current studies and has been checked by medical professionals.
- Steven A. Kemp, Dami A. Collier, Rawlings P. Datir, Isabella A. T. M. Ferreira, Salma Gayed et al.: SARS-CoV-2 evolution during treatment of chronic infection, in Nature (veröffentlicht 05.02.2021), Nature
- University College London: Significant new SARS-CoV-2 variants may emerge during chronic infection (veröffentlicht 05.02.2021), ucl.ac.uk/
This article is for general guidance only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor.