SARS-CoV-2 intra-host evolution in an immunocompromised kidney transplant patient

According to a new study published in the journal Nature Communications ,immunocompromised patients may be valuable in studying coronavirus infection in severe acute respiratory syndrome 2’s (SARS-CoV-2) evolution. German researchers documented the pathology of the virus in an individual with kidney transplant who had been persistently infected with SARS-CoV-2. Further examination revealed that the virus was carrying multiple variants nesting within the patient with immunocompromised status. This suggests that the virus was able to develop advantageous evolutionary mutations due to the weak immune system.

Study: The within-host evolution and immune escape variants of SARS are observed in patients with COVID-19 immunosuppression. Image Credit: Adao/ Shutterstock

Certain spike protein mutants could alter the conformation of the subdomain which is the target of neutralizing antibodies. The escape mutations that emerged from the immunocompromised patient resembled those found in immune-escape variants circulating around the world.

“Such escape mutants could act as the seeds for new variants that have greater potential for spreading disease, particularly when they overcome the limitations of viral fitness by further adaptation,” explained the research team.

Case report details

A man aged 58 was admitted to the hospital with a history and symptoms of autosomal domin polycystic renal disease. He also had end-stage kidney disease in 2014. The patient also had a history of coronary heart disease, arterial hypertension, hyperlipidemia, and overweight.

Due to the patient’s kidney disease and his kidney disease prognosis, he needed a transplant. A kidney transplant was available in March 2020. He underwent immunosuppressive treatment to prepare for the transplant.

The patient began to experience mild respiratory symptoms. In March 2020, coronavirus disease 2019 (COVID-19) testing revealed the patient was positive for SARS-CoV-2 and remained positive for the next 25 weeks.

Due to the lack of clarity surrounding SARS-CoV-2 in the early stages of the pandemic, doctors recommended a five-day treatment with Ivermectin. Despite the failure of the treatment, the COVID-19 infection continued to be.

The immunosuppressive treatment regimen was lowered to permit the patient to develop a stronger adaptive immune system to viruses. This led to spike-specific neutralizing antibodies. In addition, the COVID-19 infection was later treated with remdesivir for ten days. The COVID-19 tests after treatment were negative, indicating that the time to create neutralizing antibodies. the treatment with remdesivir allowed the infection to go away.

Viral genomic changes in the immunocompromised patient

Genomic sequencing has revealed the emergence of several variants of SARS-CoV-2 in the immunocompromised patient. These SARS-CoV-2 variants had many amino acid substitutions as well as deletions in spike protein. This included nucleotide changes in ORF1ab and the spike gene, ORF3a and M genes. SARS-CoV-2 mutations were found to accumulate over time which allowed for the evolution and selection of distinct variants that were beneficial to evolution.

In the spike protein there were deletions and modifications in the N-terminal domain as well as the receptor-binding motif. Two amino acid deletions in the N-terminal domain could be connected to the development of at least two variants of SARS-CoV-2 in that they alter the form of the target of neutralizing antibodies.

Therefore, the viral mutations in the variants proved successful in resisting neutralizing antibodies. Researchers discovered that the mutations found in the immunocompromised patients were similar to those that were found in escape variants in South Africa (Beta), Brazil (Gamma) and the United Kingdom (Alpha).

SARS-CoV-2 variants can be protected by neutralizing response.

One of the isolated viral variants, d105, evolved later than the other. The variant showed an insufficient response to neutralizing antibodies, which suggests that the spike protein mutations impaired the immune system’s antiviral response.

A study of mice has confirmed neutralizing antibodies from mice that survived COVID-19 infection from the d14 or d105 isolates provides broad immune protection against other infected mice. However, the mice showed a weaker overall immune response with two-fold lower levels of IgG antibodies compared to mice infected by the original strain of SARS-CoV-2.

Next, the researchers tested the neutralizing response to variants of concern like Beta and Alpha. The results revealed that neutralizing antibodies produced by mice following d105 infection were more effective at neutralizing Beta than Alpha.

In a separate study in a separate study, a lethal dose was administered to mice infected by the strain d105 up to five months prior. Mice that had neutralizing antibodies from the first infection survived and showed no symptoms or signs of infection.

The animal studies suggest previously infected individuals may show resistance to COVID-19 reinfection.

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Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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